Fornix Of Hippocampus

Fimbria-fornix (FF), the septo-hippocampal pathway, was transected to model Alzheimer's disease (AD), which is characterized by loss of cholinergic afferent fibers in hippocampus.  

Brain injury emerged in anxious OSA versus nonanxious controls in bilateral insular cortices, caudate nuclei, anterior fornix, anterior thalamus, internal capsule, mid-hippocampus, dorsotemporal, dorsofrontal, ventral medial prefrontal, and parietal cortices.  

Recombined cells were co-labelled with Neu-N, but not with GAD67, and were characterized by long range projections (corpus callosum, fornix, thalamocortical).  

RESULTS: Three WM tract regions had significantly reduced FA: 1) arcuate fasciculus in left superior temporal gyrus, 2) cingulum bundle by the posterior tail of the left hippocampus, and 3) the left body of the fornix.  

Here we used Pavlovian fear conditioning in rats to explore whether the entorhinal cortex and fornix, which are the major cortical and subcortical interfaces of the hippocampus, are also involved in the context-dependence of extinction. In contrast, rats with neurotoxic lesions in the entorhinal cortex or electrolytic lesions in the fornix did not exhibit a renewal of fear when tested outside the extinction context. Impairments in freezing behavior to the auditory CS were not able to account for the observed results, insofar as rats with either entorhinal cortex or fornix lesions exhibited normal freezing behavior during the conditioning session.  

Second, neuropsychological studies of patients with colloid cysts confirm the importance of at least one of these routes, the fornix, for episodic memory.  

The fornix is the primary efferent neural pathway of the hippocampus and has been shown to be abnormal in adults with schizophrenia. Measures of cross-sectional area and water diffusion properties were obtained on regions of interest of the fornix performed by a trained radiologist. RESULTS: The volume of the fornix was significantly smaller (10.9%) in children and adolescents with schizophrenia compared to controls (Cohen d = 0.87, p = .025). CONCLUSIONS: These findings suggest that the early stages of schizophrenia are associated with a decrease in fornix volume without microstructural white matter changes.  

Also the timing of previously reported fornix abnormalities in patients with mesial temporal sclerosis (MTS) is unknown. We report longitudinal volumetic MRI and diffusion tensor imaging (DTI) findings of the hippocampus and fornix in a patient following status epilepticus.  

CA1 efferents in the dorsal fornix were similarly transected. Fimbria transections, but not dorsal fornix transections, resulted in deficits for the encoding of spatial information during learning of a Hebb-Williams maze. Dorsal fornix, but not fimbria, transections resulted in deficits for retrieval of spatial memory during learning of a Hebb-Williams maze.  

While some memory inadequacies in OSA may result from earlier-described structural deficits in the hippocampus, mammillary body injury also could contribute, since these structures receive projections from the hippocampus via the fornix, project heavily to the anterior thalamus, and have been implicated in other conditions with memory deficiencies, such as Korsakoff's syndrome.  

BACKGROUND: The fornix is a major projection of the hippocampus to and from other brain regions. A previous diffusion tensor imaging (DTI) study has reported disrupted integrity of the fornix in patients with schizophrenia. However, functional significance of the DTI abnormalities of the fornix in schizophrenia has not been fully studied yet. We investigated an association between DTI abnormalities of the fornix and impairment of memory organization in schizophrenia. METHODS: Thirty-one patients with schizophrenia and 65 age- and gender-matched healthy controls underwent DTI, and fractional anisotropy (FA) and mean diffusivity (MD) were measured in cross-sections of fornix tractography. RESULTS: Statistically significant reduction of FA and increase of MD were found in the fornix of patients with schizophrenia compared with controls with no significant lateralization. A significant patients-specific correlation was found between increased MD in the left fornix and lower scores on utilization of semantic organization in the verbal learning task. In addition, increased MD in the right fornix showed a patients-specific association with poorer performance on the category fluency test, which indexes organization of long-term semantic memory. CONCLUSIONS: These results indicate that disrupted integrity of the fornix contributes to impaired memory organization in schizophrenia..  

The hippocampal tail and fimbria-fornix are disrupted posteriorly.  

The medial septum diagonal band area (MS/DB) projects to the hippocampus through the fornix/fimbria pathway and is implicated in generating hippocampal theta oscillations. Here, we investigated the physiological role of hippocamposeptal feedback to the MS/DB in a complete in vitro septohippocampal preparation containing the intact interconnecting fornix/fimbria pathway. We next determined the mechanism underlying the rebound spiking that followed the IPSPs in MS/DB GABAergic neurons using phasic electrical stimulation of the fornix/fimbria pathway.  

BACKGROUND: Reports of amnesia due to bilateral fornix lesions are rare. A unilateral right fornix lesion is not known to cause an amnestic confabulatory syndrome. OBJECTIVE: To investigate the role of right fornix lesion in amnesia, the association of confabulation with executive disorders, and to evaluate the long-term recovery of memory and executive functions after surgical removal of a pilocytic astrocytoma in the right orbitofrontal region extending to the right fornix. CONCLUSIONS: The authors hypothesize that the lesion of the right fornix was sufficient to cause amnesia by disconnecting the hippocampal formations from the anterior thalamic nuclei and mammillary bodies and interrupting the cholinergic efferents to the hippocampus from the medial septum, according to the extended hippocampal system framework. Sparing of the left fornix may be sufficient to ensure a good recovery of memory.  

The fornix body was reconstructed by diffusion tensor tractography, and the integrity of this tract was evaluated using fractional anisotropy (FA). Meanwhile the mean FA of the fornix body was significantly reduced in patients, indicating the damage in the hippocampal anatomical connectivity in schizophrenia.  

This study explored the putative role of the principal 5-hydroxytryptamine (5-HT) neurones that project to the hippocampus from the median raphe nucleus in this response to an aversive environment by lesioning the 5-HT fibres that project through the fornix/fimbria and cingulum bundles.  

To investigate such a role, six macaque monkeys received a bilateral transection of the fornix to disconnect subcortical inputs and outputs of the hippocampus. In the initial acquisition stage, control and fornix animals were equally proficient in learning the discriminations. In the five reassigned stages, however, monkeys with fornix transection made on average three times as many errors as the controls in learning the discriminations. These findings are consistent with other recent evidence for a role beyond the spatial domain for the fornix in monkeys..  

The hippocampus and mammillary body are small and the fornix is thin; in contrast, the amygdaloid complex is large and the cortex of the limbic lobe is extended.  

In addition, ICSS facilitates operant and spatial learning, and ameliorates fornix-lesion induced behavioral deficits.  

Experiment 2 assessed the impact of fornix lesions on the acquisition of one version of this task (CS+ 1.5s, CS- 0.5s). Experiment 3 examined whether rats with either fornix or hippocampal lesions affected discriminations between 12.0 s and 3.0 s stimuli. The results not only reveal that neither the fornix nor the hippocampus is necessary for distinguishing temporal intervals within the ranges tested but also showed how under some circumstances these lesions can leave trace conditioning intact..  

Limbic structures that show consistent patient/control differences in both postmortem and neuroimaging studies include the anterior cingulate and hippocampus, although differences in the amygdala, parahippocampal gyrus, and fornix have also been observed.  

fornix lesions did not affect either version of the task, demonstrating that the extended hippocampal system has no role in stimulus-outcome (S-O) associations.  

Simulated transection of the fornix, effectively eliminating hippocampal and prefrontal influence over the nucleus accumbens, abolishes normal contextual modulation of behavior.  

We have previously found that EPO given to fimbria-fornix transected rats at the moment of injury is able substantially to improve the posttraumatic acquisition of allocentric place learning tasks administered in a water maze as well as in an 8-arm radial maze. Consequently, we presently studied the effects of similarly administered EPO in fimbria-fornix transected and control operated rats, respectively--evaluating the posttraumatic behavioural/cognitive abilities in a spatial delayed alternation task performed in a T-maze. Administration of EPO to the hippocampally injured rats was associated with a substantial reduction of the lesion-associated behavioural impairment--while such an impairment was clearly seen in the saline injected fimbria-fornix transected group.  

Do lesions of the fornix or the hippocampus impair the performance of spatial conditional associative learning tasks, and to what extent does damage to these brain structures result in comparable deficits in this type of spatial behavior? The available evidence is not clear. In the present study, rats with lesions of the fornix, hippocampus, and normal control animals were trained on two spatial-visual conditional learning tasks in which they had to form arbitrary associations between visual stimuli and the context in which these stimuli were embedded. Rats with fornix transection were able to learn both conditional tasks at a rate comparable to that of normal control animals, but rats with hippocampal damage were severely impaired under both conditions. In addition, the results argue that the fornix is not necessary for the acquisition of certain spatial conditional learning tasks and that this brain structure cannot be used as an indicator of hippocampal dysfunction under all learning situations..  

We therefore investigated the effects of 4OH-GTS-21, a selective partial agonist for these receptors, on septohippocampal cholinergic and GABAergic neuron survival following fimbria fornix (FFX) lesions in three strains of mice: C57BL/6J wild type mice; human presenilin-1 mutant M146L (PS1) transgenic mice; and mice expressing both mutant PS1 and Swedish mutant K670N/M671L amyloid precursor protein (APP).  

The current study investigated the effects of galantamine (0.0 or 3.0mg/kg) in rabbits sustaining knife-cut lesions to the fimbria-fornix, a major projection pathway connecting the hippocampus to cortical and subcortical brain structures involved in the formation of long-term memories. Experiment one assessed the effects of knife-cut lesions to the fornix or sham surgeries on trace eyeblink (EB) conditioning. Results indicate that fornix lesions significantly retarded EB conditioning when trace parameters were employed. Experiment 2 assessed whether treatment with galantamine would reverse the deficits caused by fornix damage. Results indicate that 3.0mg/kg GAL reversed trace EB conditioning deficits in animals with fornix knife-cut lesions.  

A dorsal pathway from the dorsal third of field CA1 innervates moderately the retrosplenial area; a moderately strong ventral pathway from the ventral two thirds of field CA1 passing through the longitudinal association bundle sends offshoots to visual, auditory, somatosensory, gustatory, main and accessory olfactory, and visceral areas-as well as the basolateral amygdalar complex and the agranular insular and orbital areas; and a cortical-subcortical-cortical pathway through the fornix from the whole longitudinal extent of field CA1 innervates rather strongly a rostral region that includes the tenia tecta along with the anterior cingulate, prelimbic, infralimbic, and orbital areas.  

The acquisition of a spatial delayed alternation task in a T-maze was studied in four groups of rats: animals in which the fimbria-fornix had been transected bilaterally, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. Both of the fimbria-fornix transected groups were significantly impaired even when compared to the group given prefrontal cortical ablations in isolation. The two fimbria-fornix lesioned groups did, however, exhibit levels of functional recovery. The group in which both structures had been lesioned demonstrated a task acquisition, which was significantly inferior to that of the group given fimbria-fornix transections in isolation. This expansion of the inter-trial delay rather selectively impaired the task performance of the group given fimbria-fornix transections in isolation. Consequently, both during the acquisition period and in one of the challenges a differentiation of functional recovery was seen between the combined lesioned group and the group given fimbria-fornix lesions only. This indicates that even in case of a spatial delayed alternation task the prefrontal cortex normally contributes significantly to mediation of posttraumatic functional recovery after isolated lesions of the fimbria-fornix.  

The relationship of the entorhinal cortex (EC) and fimbria-fornix (FF) in unreinforced spatial (latent) learning was studied using the conditioned-cue-preference task on an eight-arm radial maze. These results indicate that the acquisition of information during unreinforced exploration of a novel environment requires an intact circuit involving the dorsal EC and fimbria fornix.  

In addition, reduced memory scores correlated in the expected direction with magnetic resonance imaging (MRI) of the hippocampus and diffusion tension imaging (DTI) of the fornix for subsets of both patients and controls that had available these structural imaging measures. Reduced executive functioning also correlated with lower fornix integrity for the patient subset.  

The distribution of neurons contributing to the fornix was mapped by placing the retrograde tracer horseradish peroxidase (HRP) in polyacrylamide gels in different medial to lateral locations within the fornix of three rhesus monkeys (Macaca mulatta). The HRP was placed from 3 to 5 mm caudal to the descending columns of the fornix. The hippocampal formation, including the subiculum and presubiculum, together with the entorhinal cortex (EC) and perirhinal cortex (area 35) contribute numerous axons to the fornix in a topographical manner. In contrast, the lateral perirhinal cortex (area 36) and parahippocampal cortical areas TF and TH only contained a handful of cells labeled via the fornix. The medial fornix originates from cells in the caudal half of the subiculum, the lamina principalis interna of the caudal half of the presubiculum, and from the perirhinal cortex (area 35). The intermediate portion of the fornix (i.e., that part midway between the midline and most lateral parts of the fornix) originates from cells in the rostral half of the subiculum and prosubiculum, the anterior presubiculum (only from the lamina principalis externa), the caudal presubiculum (primarily from lamina principalis interna), the rostral half of CA3, the EC (primarily 28I and 28M), and the perirhinal cortex (area 35). The lateral parts of the fornix arise from the rostral EC (28L only) and the most rostral portion of CA3. Subcortically, the medial septum, nucleus of the diagonal band, supramammillary nucleus, lateral hypothalamus, dorsal raphe nucleus, and the thalamic nucleus reuniens all send projections through the fornix, which presumably terminate in the hippocampus and adjacent parahippocampal region. These results not only help to define those regions that project via the fornix, but also reveal those subcortical projections to the hippocampal formation most likely to rely entirely on nonfornical pathways..  

We demonstrated previously that when hippocampal-dependent learning and plasticity are compromised by fornix lesions, behaviorally induced expression of the immediate early gene, Arc, is correspondingly low. The medial septum and the vertical diagonal band are major sources of subcortical afferents that innervate the hippocampus via the fornix. Here we assessed the specific contribution of cholinergic afferents from these regions to the impairments in spatial learning and behavioral induction of Arc transcription produced by fornix lesions. In marked contrast to the effects of complete fornix transection, quantitative in situ autoradiography revealed no differences in Arc mRNA expression between sham and lesion animals in CA1, CA3 or stratum radiatum. The conclusion from these data is that cholinergic deafferentation alone cannot account for the spatial learning deficits or impaired behavioral induction of Arc transcription produced by fornix lesions..  

Accordingly, the expression of mRNAs for corticotrophin-releasing hormone (CRH), the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) in the PVN was examined by in situ hybridisation in rats subjected to transection of the fornix. Significant increases in CRH, MR and GR mRNAs were observed in the parvocellular PVN after fornix transection (FT).  

Degeneration of axotomized GABAergic septohippocampal neurones has been shown to be enhanced in ciliary neurotrophic factor (CNTF)-deficient mice following fimbria-fornix transection (FFT), indicating a neuroprotective function of endogenous CNTF.  

Theta rhythmicity in the supramammillary area remained after septal blockade, and we used this to trigger electrical stimulation of the fornix superior.  

Lesions restricted to the hippocampal formation and/or extended hippocampal system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving familiarity-based memory relatively intact. An amnesic patient (A.D.) with bilateral fornix and septal nuclei lesions failed to recognize details pertaining to personal past events only when recollection was required, during recognition of episodic details. By comparison, another amnesic person (K.C.) with extensive MTL damage (involving extra-hippocampal MTL structures in addition to hippocampal and fornix lesions) had very poor recognition and no recollection of either episodic or generic/semantic details.  

These results were not reproduced after lateral axotomy of the fimbria fornix, indicating a specific role for Sema6C variants in the generation and/or stability of entorhino-hippocampal synapses.  

This study examined whether the cooperation of the hippocampus, and anterior thalamus via the fimbria-fornix is involved in the spatial memory. We compared the effect of contralateral lesions (Contra) with ipsilateral lesions (Ipsi) of the fimbria-fornix and anterior thalamus on the performance of an object exploration task and the Morris water maze task. If the hippocampus and anterior thalamus take part in a same functional system via fornix, the performance of Contra group will be more disruptive than that of Ipsi group. These results indicate that contralateral, but not ipsilateral lesion caused deficits in spatial memory, supporting the notion that the functional cooperation of hippocampus and anterior thalamus via fornix is vital for spatial memory..  

Structural neuroimaging confirmed bilateral lesions to the fornix and a small lesion in the basal forebrain. Because the fornix and basal forebrain lesions disrupted major afferent and efferent pathways of the hippocampus, it was concluded that the integrity of the hippocampus and its projections are needed to retain and/or recover autobiographical memories no matter how old they are.  

Animal model of AD was established with fimbria-fornix transection.  

Prompted by the theoretical prediction that damage to the hippocampal system should abolish exploratory behavior, the present study examined exploratory movements in control monkeys (CON) and monkeys with transection of the fornix (FNX), a major input/output pathway of the hippocampus. These observations are consistent with the idea that interrupting normal hippocampal system function by means of fornix transection is detrimental to learning about the spatial layout of environments. We therefore suggest that while monkeys with fornix transection still display intact locomotor and exploratory behavior patterns, their new learning of visuospatial context is impaired..  

METHODS: Fractional anisotropy and apparent diffusion coefficient for uncinate fasciculus, stria terminalis, fornix, and cingulum were measured in 7 right-handed children (5 girls and 2 boys; mean age: 9.7 +/- 2.6 years) with a history of early severe socioemotional deprivation in Eastern European orphanages and compared with similar measurements in 7 right-handed normal children (4 girls and 3 boys; mean age: 10.7 +/- 2.8 years).  

We hypothesized that if the fetal hippocampal formation is functional in late gestation, loss of hippocampal input to the HPA axis following fetal fornix transection would change gestation length in comparison to controls. At 118-121 days of gestation (dG), stereotaxic technique was used in fetal sheep to sham transect (SHAM; n = 8) or transect (FXTX; n = 6) the dorsal fornix at the level of the hippocampal commissure.  

These divergent views were examined in experiments using electrolytic Lesions of fimbria-fornix (FF) or radiofrequency or neurotoxic Lesions of MT of rats subsequently trained to find a stable visible (experiment 1) or hidden platform (experiments 2 and 3) in a water maze (WM) pool.  

We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults..  

Long-term protection against severe forebrain ischemia can be conferred by fimbria-fornix (FF) deafferentation, which interrupts the afferent input to CA1.  

To differentiate the contributions of each, we assessed the induction of Arc transcription in rats with fornix lesions that impair hippocampal learning yet leave cortical connectivity and neuronal firing essentially intact. During the same task, rats with fornix lesions learned to approach a visible platform but did not learn its spatial location. Rats with fornix lesions had normal baseline levels of hippocampal Arc mRNA, but unlike normal rats, expression was not increased in response to water maze training. The integrity of signaling pathways controlling Arc expression was demonstrated by stimulation of the medial perforant path, which induced normal synaptic potentiation and Arc in rats with fornix lesions. The results further imply that fornix lesions may impair memory in part by decoupling neuronal activity from signaling pathways required for long-lasting hippocampal synaptic plasticity..  

We previously found that EPO given to fimbria-fornix transected rats at the moment of injury could substantially improve the posttraumatic acquisition of an allocentric place learning task when such a task is administered in a water maze. Consequently, here we studied the effects of similarly administered EPO in fimbria-fornix transected and control operated rats, respectively, evaluating the posttraumatic behavioral/cognitive abilities in an allocentric place learning task administered in an 8-arm radial maze. The administration of EPO to the hippocampally injured rats was associated with a virtually complete elimination of the otherwise severe behavioral impairment caused by fimbria-fornix transection.  

Lesions of the fimbria-fornix impaired the water and salt CCPs but not the salt LCP, while lesions of the entorhinal cortex impaired the salt LCP but not the CCPs. In contrast, the CCPs depend on the amygdala and a circuit that includes the hippocampus and fimbria-fornix, possibly as a conduit of motivational information from subcortical structures..  

The early fetal telencephalon impar also contains the first commissural fibers and fornix bundles in the septal area.  

We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected.  

The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia. METHODS: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. RESULTS: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. Reduced hippocampal volume was correlated with increased mean D(m) and reduced cross-sectional area of the fornix for patients. CONCLUSIONS: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia..  

All of the hippocampal and parahippocampal projections to the mammillary bodies appeared to use the fornix as a route.  

The brain areas of interest included the fornix, medial prefrontal cortex, mediodorsal (MD) thalamic nucleus, and nucleus accumbens. Damage to the fornix impaired some fear responses (freezing, ultrasonic vocalizations, defecation, and approach/avoidance) while leaving conditioned fear expression of heart rate and urination unaltered.  

One hundred and fifty scans were randomly selected for the measurement of HC volumes beyond the opening of the crus of the fornix by manual tracings on T1-weighted images by a trained operator.  

We also provide evidence that despite the strong connectivity between these cortical regions and the hippocampus, the hippocampus, as evidenced by lesions of the fornix, has a distinct function of its own--combining information about objects, positions, and contexts..  

Micro-injection of the 5-HT neurotoxin 5,7-dihydroxytryptamine into the fimbria-fornix (3.0 microg/side) and the cingulate bundle (1.8 microg/side) depleted hippocampal 5-HT locally but did not change cell proliferation 3 weeks after the surgery.  

The hippocampus receives substantial input from the medial septum/diagonal band of broca (MS/DB) via the fibria-fornix (FF).  

In previous work, the authors found that fornix transections impaired the ability of macaque monkeys (Macaca mulatta) to learn conditional motor associations between the nonspatial features of visual stimuli and nonspatially differentiated responses. In the present study, they found that significant 1-trial learning of such associations also depended on the fornix. Furthermore, removal of the hippocampus, subiculum, and subjacent parahippocampal cortex, added to fornix transection, had no effect, thus demonstrating that fornix transections eliminated the contribution of the hippocampal system.  

However, neuroprogenitor proliferation in the DG is reduced after fimbria-fornix lesions but not after entorhinal deafferentation, which supports the view that neuroprogenitor proliferation and/or differentiation in the DG are controlled from basal forebrain/septal neurons..  

Gene expression is studied by RT-PCR in ovariectomized female rats with and without estrogen supplementation within the physiological estradiol range and in rats with complete fimbria-fornix transactions treated with estrogen or vehicle. To clarify mechanisms of estrogen transduction in cholinergic neurons, we study the effects of estrogen treatment on fimbria-fornix-lesioned mice with genetic ablations of ER subtypes alpha and beta.  

(1) To investigate the effects of long-term cholinergic deafferentation, we lesioned the fimbria-fornix pathway in our AD-model mice at 7 months of age, and 11 months post-lesion the mice were sacrificed for histopathological analysis. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus, but the lesion did not result in an alteration in hippocampal A deposition and inflammation (i.e., numbers or staining density of astrocytes and microglia).  

Although bilateral fimbria-fornix (FF) lesioning impairs spatial performance in animals, the literature is equivocal regarding its effects on hippocampal long-term potentiation (LTP).  

METHODS: In 45 patients with unilateral mesial temporal lobe epilepsy, histologically proven Ammon's horn sclerosis, and uneventful postoperative course, volumes of the hippocampus, hemisphere, amygdala, entorhinal cortex, mamillary body, and fornix were measured by using a T(1)-weighted 3-D gradient-echo sequence with roughly isotropic (1.17 x 1.17 x 1-mm) voxels. RESULTS: Hippocampal, hemispheric, entorhinal cortex, mamillary body, and fornix volumes, but not amygdalar volumes, were significantly smaller on the operated-on than on the non-operated-on side and significantly smaller in patients compared with controls. No volume differences of the hippocampus, hemisphere, amygdala, entorhinal cortex, mamillary body, and fornix existed between seizure-free (Engel class IA) and non-seizure-free patients (Engel class IB-IV).  

In the current study, the memory effects of clozapine and nicotine administration were determined in rats with lesions of the fimbria-fornix, a fiber bundle which carries cholinergic and other projections between the septum and the hippocampus. Then, 13 rats received bilateral knife-cut lesions of the fimbria-fornix, while 14 rats underwent sham surgery. Fimbria-fornix lesions also caused a significant (P<0.05) memory impairment. In contrast to its effects in controls, clozapine (1.25 mg/kg) significantly (P<0.05) attenuated the working memory deficit caused by fimbria-fornix lesions. This study demonstrates the efficacy of clozapine in improving working memory in fimbria-fornix-lesioned rats, whereas it causes impairments in intact rats.  

The acquisition of a water maze based task requiring egocentric spatial orientation in the absence of distal cues was studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats that received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham-operated control group. Behavioural challenges in the form of a no-platform session and two reversals of platform position demonstrated that while the sham-operated control group and the group subjected to fimbria-fornix transections in isolation utilized rather pure egocentric orientation strategies, the two prefrontally lesioned groups (and especially the combined lesion group) employed a different set of solution strategies which at least partly relied on a "circling" method.  

Stimulation of either perforant path or fimbria fornix induced a prolonged afterdischarge pattern peaking at 200 Hz fast, 20 Hz beta, and 2 Hz Delta frequencies.  

This study examined the distribution of vesicular glutamate transporter 2 (VGLUT2)-immunoreactive neuronal structures in the ipsilateral and contralateral hippocampi of unilateral fimbria/fornix transected, unilateral entorhinal cortex ablated, and intact female and male rats. The fimbria/fornix transection caused a significant reduction in the density of VGLUT2-positive boutons only in the CA2 field, while entorhinal cortex ablation elicited no change in fiber density in any of the areas analyzed.  

OBJECTIVE: The gross morphology and morphometry of the hippocampus, fornix, and corpus callosum in patients with severe non-missile traumatic brain injury (nmTBI) without obvious neuroradiological lesions was examined and the volumes of these structures were correlated with performance on memory tests. RESULTS: In comparison with control subjects matched in terms of gender and age, volume reduction in the hippocampus, fornix, and corpus callosum of the nmTBI patients was quantitatively significant. Immediate free recall of word lists correlated with the volume of the fornix and the corpus callosum. Delayed recall of word lists and immediate recall of the Rey figure both correlated with the volume of the fornix. Delayed recall of the Rey figure correlated with the volume of the fornix and the right hippocampus. CONCLUSION: These findings demonstrate that in severe nmTBI without obvious neuroradiological lesions there is a clear hippocampal, fornix, and callosal volume reduction.  

Fimbria-fornix lesions made before, but not after, PE, and hippocampus lesions made at either time, blocked the discrimination, suggesting that the 2 structures processed different information. A hippocampus/fimbria-fornix system and an amygdala system process different information about the same learning situation simultaneously and in parallel..  

Both fornix transection and selective neurotoxic hippocampal lesions severely impaired memory performance, but cue and motivational discrimination, as well as stimulus-reward associations, were preserved.  

The results of the correlated light and electron microscopic double-labeling immunohistochemistry for VGLUT2 and PV, and single immunostaining for VGLUT2 in colchicine-treated animals, showed that (1) VGLUT2-containing boutons establish asymmetric synaptic contacts with PV-positive perikarya and dendrites; (2) a large population of VGLUT2-immunoreactive neurons is located primarily in the posterior division of the septum; and (3) following surgical fimbria/fornix transection and septal undercut, most VGLUT2-containing axons, including those terminating on MSDB PV cells, remains intact.  

The ability of fimbria-fornix bilateral axotomy to elicit calpain and caspase-3 activation in the rat septohippocampal pathway was determined using antibodies that selectively recognize either calpain- or caspase-cleaved products of the cytoskeletal protein alphaII-spectrin. Calpain-cleaved alphaII-spectrin immunoreactivity was observed in cholinergic fibers coursing through the fimbria-fornix, but not in pyramidal neurons of the dorsal hippocampus, suggesting that degenerating cholinergic nerve terminals were the source of calpain activity in the dorsal hippocampus following axotomy.  

The subsequent axonal transport of Mn(2+) highlighted the principal extrinsic projections from the posterior hippocampal formation via the fimbria and the precommissural fornix to the dorsal part of the lateral septal nucleus.  

These results indicate that the whole of the inferotemporal cortex-anterior thalamic circuit, which passes via the hippocampus, fornix, mamillary bodies and mamillothalamic tract, is essential for the topographical analysis of information about specific objects in different positions in space.  

Rats receiving intrahippocampal injections of 192 IgG-saporin (SAP-HPC), fimbria-fornix lesions (FF), or sham control surgeries were tested in a series of delayed matching (DMTP)- and nonmatching (DNMTP)-to-position tasks. Results demonstrate the importance of the fimbria-fornix fiber system in spatial short-term memory but suggest that the cholinergic septohippocampal component of this pathway is not required for successful delayed matching (or nonmatching)-to-position performance..  

The concentration of metallothioneins, evaluated by immunohistochemistry, as well as area-specific protein expression, were found in the following quantitative order: corpus striatum, cerebellum, mesencephalon, hippocampus with fornix, parts of thalamus, and pons.  

L1-mRNA levels were also increased in grey matter structures such as the septum nuclei and the habenula, but remained unchanged in most of the grey matter structures analyzed (cerebral cortex, basolateral amygdaloid nucleus, hippocampus, thalamic and hypothalamic nuclei, basal ganglia and subventricular zones) and also in a few white matter structures (fornix and fasciculus retroflexus).  

STZ causes microglial activation and specific damage to myelinated tracts in the fornix through generation of oxidative stress, thereby disrupting connections between the septum and hippocampus.  

Plasma albumin was observed in the parenchyma of the brain in cortex, thalamus, hypothalamus, corpus callosum, fornix, hippocampus, midbrain, subcallosal bundle, and cerebellar Purkinje cells.  

Infusions of tetrodotoxin (TTX) were used to induce reversible lesions in the fimbria fornix, medial septum, dorsal hippocampus, and ventral hippocampus. Tetrodotoxin lesions of the fimbria fornix increased both open arm exploration and the number of shocks taken by the rats, while having no effect on burying behavior.  

STZ caused selective injury to myelin and axons in the fornix and hippocampus in association with activation of microglia. These could result from a disruption of the communication through myelinated axons in the fornix connecting the septum and the hippocampus, and through other myelinated axons adjacent to the ventricles.  

We have analysed changes in gene expression patterns occurring as a consequence of postcommissural fornix transection at a time when spontaneous axonal growth has ceased at the lesion site. In addition, we observed that within the subiculum, where the fornix axons originate, neuronal Oct-6 was induced and NG2 was down-regulated, indicating that axotomized neurons as well as glial cells react at the level of gene expression to remote axotomy..  

Recent studies have shown that chronic stimulation of the subthalamic nucleus, fornix, or hippocampus may be effective in attenuating seizure frequency in animal models and in patients with intractable epilepsy.  

In the present study, we examined whether the VH influence on PPI and its dopaminergic regulation is dependent on the integrity of the VH-accumbens projection via the fornix. First, the PPI-disruptive effects of intra-VH NMDA infusion were assessed after sham or electrolytic transection of the fornix. Second, the PPI-disruptive effects of apomorphine were assessed 1 month after excitotoxic or electrolytic lesions of the VH, or after fornix transection. Intra-VH N-methyl-D-aspartate infusion significantly disrupted PPI; this effect was unaffected by fornix lesions. The PPI-disruptive effects of apomorphine were significantly enhanced by excitotoxic or electrolytic lesions of the VH, but not by fornix transection.The influence of the VH on PPI and its dopaminergic regulation does not appear to be mediated via the fornix.  

The effect of memory on hippocampal neuronal activity was assessed as rats performed a spatial task that was impaired by fornix lesions.  

fornix-transected and sham-operated rats were trained on radial maze cue tasks in which the relative positions of the cues were either fixed (F condition) or varied (V condition) across trials. With proximal stimuli, fornix-transected rats were transiently impaired in the V condition and performed as well as controls in the F condition. However, using extramaze stimuli, fornix-transected rats were severely impaired in the V condition but performed normally in the F condition.  

From E15 to P3, CS became expressed between the hippocampal commissure and the third ventricle and at the caudal borders of the fornix columns.  

Transection of the fimbria/fornix (FF) had no significant effect on the synaptic density in non-GDX males.  

The simultaneous occurrence of ipsilateral fornix (F) and mamillary body (MB) volume loss was checked also. In 29 (25.2%) cases there were ipsilateral fornix volume loss and in 10 (34.5%) of this there were also ipsilateral MB changes. There were fornix changes in 15 (34.8%) cases and MB volume loss in 5 (11.6%) cases.  

INTRODUCTION: Numerous reports show that lesions to hippocampus afferents, such as the entorhinal cortex (EC) and the fimbria fornix (FF), exert an effect on memory in rodents.  

To determine the long-term effects of this NGF-expression on neuron function, fimbria-fornix (FF) lesions were conducted 6 months after NGF gene transfer.  

Robust EphA4 expression was also found in the hippocampus and fornix, and cells and tracts in the striatum.  

BACKGROUND: Previous magnetic resonance imaging (MRI) studies have shown concurrent fornix atrophy in a large proportion of patients with hippocampal atrophy. The contribution of the fornix as an independent preoperative determinant of surgical outcome is unknown. OBJECTIVE: To evaluate the contribution of the fornix as a determinant of surgical outcome in patients with preoperatively determined temporal lobe epilepsy. Thirty-five patients (44.9%) had unilateral isolated hippocampal atrophy exclusively on MRI volumetry, 29 (37.2%) had unilateral hippocampal atrophy with ipsilateral fornix atrophy, and 6 (7.7%) had isolated fornix atrophy without hippocampal atrophy. Twenty-eight patients (80%) in the unilateral hippocampal atrophy group were seizure free (ie, Engel class 1: patients who are completely seizure free with no aura and who do not receive antiepileptic drugs) compared with 21 patients (73%) in the fornix and hippocampal atrophy group (P =.57). All 6 patients with isolated fornix atrophy achieved an Engel's class 1 outcome. CONCLUSIONS: These findings suggest that identification of fornix atrophy with or without associated hippocampal atrophy is not an important preoperative determinant of surgical outcome. However, in the presence of a normal hippocampus, fornix atrophy may be valuable in predicting seizure-free outcome..  

Using fimbria-fornix transection as a model, we examined whether responses of GABAergic and cholinergic septohippocampal neurons to axotomy are altered in mice lacking CNTF.  

The fimbria-fornix was lesioned by a unilateral-knife cut and the brain was processed for 125I-Ang IV binding, acetylcholinesterase, and cresyl violet staining. Unilateral lesions of the fimbria-fornix significantly reduced acetylcholinesterase staining in the ipsilateral hippocampus.  

Rats with fornix transection, or with cytotoxic retrohippocampal lesions that removed entorhinal cortex plus ventral subiculum, performed a task that permits incidental learning about either allocentric (Allo) or egocentric (Ego) spatial cues without the need to navigate by them. fornix and retrohippocampal-lesioned groups learned NC problems at a similar rate to sham-operated controls and showed as much facilitation of learning by added spatial cues as did the controls; therefore, both lesion groups must have encoded the spatial cues and have incidentally learned their associations with particular constant scenes.  

Further, to investigate the effects of long-term deafferentation, in a second experiment we cut the fimbria-fornix and analyzed the brains 11 months post-lesion.  

METHODS: Lesioning of the rat fimbria-fornix area was achieved by aspiration through the cortex; animals were killed 4 weeks later.  

Moreover, the D1 receptor agonist SKF 38393, but not the D2 receptor agonist quinpirole, mimicked the effects of DA, although a small population of neurons exhibited a D1-mediated facilitation of the EPSP amplitude following fornix stimulation.  

MD stimulation inhibited PFC neuron firing (approximately 100 msec duration) evoked by fimbria/fornix (FF) stimulation in a majority of neurons tested.  

In experiment 2, the retardation of reinforced CCP learning by involuntary unreinforced pre-exposure was eliminated by fimbria-fornix lesions made before pre-exposure but was unaffected by fimbria-fornix lesions made after pre-exposure but before training. An intact fimbria-fornix is required for acquisition but not expression of this form of learning.  

the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve.  

fornix transection impaired the learning of these associations, even though both the stimuli and the responses were nonspatially differentiated, and this deficit persisted for at least 2 years. fornix-transected monkeys were impaired in learning new stimulus-response associations even when the stimuli were highly familiar. In contrast to these effects, fornix transection did not impair performance when familiar stimuli instructed a response according to an already-learned association, which shows that the deficit was one of learning new associations rather than one of retention or retrieval of previously learned ones. Taken together, these results show that fornix transection causes a long-lasting impairment in associative learning outside of the spatial domain, in a manner consistent with theories of hippocampal-system function that stress a general role in the rapid acquisition of associative knowledge..  

To examine the regeneration capacity of dorsal septohippocampal neurons in the presence of an artificial growth-promoting substrate, biocompatible polymeric hydrogels were implanted between the septum and the hippocampus in a fimbria-fornix lesion cavity. These results confirm the regeneration capacity of severed septohippocampal neurons into polymeric substrates used as a bridge inserted in a fimbria-fornix lesion cavity.  

After learning the task, all rats received surgical implantation of stimulating electrodes in both the fornix and the perforant path and recording electrodes, bilaterally in the hippocampus. During the intertrial interval, rats received single-pulse electrical stimulation of either the fornix or perforant path. In this experiment, hippocampal theta was reset after all three stimulus conditions (light, perforant path, and fornix stimulation), with the greatest degree of reset occurring after the fornix stimulation. The results suggest that activation of the perforant path and fornix may underlie theta reset and provide a mechanism by which the hippocampus may enhance cognitive processing..  

In the present experiment, sham-operated (SH) and fornix-transected (FX) rats were trained on a new nonspatial, odor-guided task.  

Robust EphA4 expression was also found in the hippocampus and fornix, and cells and tracts in the striatum.  

Structures damaged include the corpus callosum, corticospinal tract, and fimbria/fornix projections from the hippocampus.  

Special attention is directed towards the development of the fornix and hippocampus as a hippocampal commissure is a prerequisite of normal hippocampal development.  

In adult rats, both a single administration or seven daily injections of Neotrofin at 10, 30 or 100 mg/kg intraperitoneally increased HO-1 immunoreactivity in neurons of the hippocampal formation and its connections including CA1-4, fornix, septal nuclei, hippocampal commissure, septohippocampal nucleus, fimbria, anteroventral thalamic nucleus, frontal and parietal cortex.  

Male Long-Evans rats sustained injections of 5,7-dihydroxytryptamine (5,7-DHT) into the fimbria-fornix and the cingular bundle or/and intraseptal injections of 192 IgG-saporin to induce serotonergic or/and cholinergic hippocampal denervations; Sham-operated rats served as controls.  

Lesions of the fimbria-fornix (FF) tract cause profound impairments of cognitive ability in animals.  

The purpose of the present study was threefold: develop a task in which mice center their exploration from a home base, determine whether the exploratory behavior is organized, and evaluate the role of fimbria-fornix lesions on exploration. Video records of control and fimbria-fornix mice were made in both light and dark (infrared light) conditions. The bedding-centered behavior and outward trips of the fimbria-fornix mice were similar to those of the control mice, but significantly fewer direct return trips occurred. Because the fimbria-fornix lesions disrupted the homeward component of exploratory trips, we conclude that the fimbria-fornix may contribute to dead reckoning in mice.  

To address this issue, sham-operated (SH) and fornix-transected (FX) rats were trained and tested on the place task in the eight-arm radial maze.  

The fimbria-fornix (FF) is the main subcortical input to the hippocampus.  

To investigate the relation between cholinergic neurotransmission and APP metabolism, and the possible role of cholinergic dysfunction in the development of amyloid neuropathology, we lesioned the fimbria-fornix pathway in APP+PS1 double transgenic mice, at 5 and 7 months of age. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus at both time points. At 11 months postlesion, the fimbria-fornix lesion did not result in an alteration in either the hippocampal Abeta levels or the extent of Abeta deposition, as assessed by amyloid plaque counts and image analysis of Abeta load in the 18-month-old APP+PS1 mice.  

To enhance a divergence in the ability for spatial performance, some of the animals received fimbria-fornix (FF) transection 14 days before the experiments.  

Lesions of the anterior thalamus in macaques produce impairments which resemble those seen after lesions of the fornix-mamillary pathway, which carries projections from the hippocampus to the anterior thalamus, while lesions of the mediodorsal thalamus, which receives inputs from frontal and temporal cortex, produce moderate impairments on a wider range of memory tasks. Monkeys with lesions of both thalamic nuclei were severely impaired on retention and new learning of examples of the visuospatial conditional task, a task which is specifically impaired by lesions of the fornix or hippocampus. These results suggest that the mediodorsal thalamus and the anterior thalamus are both involved in processing the output of the hippocampal-fornix-thalamic circuit.  

These hippocampal projections, which coursed through the fornix, showed a rostrocaudal gradient as more arose in the rostral hippocampus. These cortical inputs were less reliant on the fornix.  

Rats with lesions of the fornix, the hippocampus, or normal control animals were trained on a visual-spatial conditional associative learning task in which they had to learn to go to a particular location based on the presence of a specific visual cue; the rats approached the cues from different directions. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals. Both the fornix and the hippocampal animals were significantly impaired on a spatial working memory task, the eight-arm radial maze. These findings suggest that, under certain conditions, a functional dissociation exists between the effects of damage to the fornix or the hippocampus and that the fornix may be only selectively involved in spatial learning and memory..  

To assess the behavioral consequences of amyloid accumulation in the hippocampal formation, we compared the effects of APP+PS1 (AP) genotype and fimbria-fornix (FFX) transection, either alone or combined, on various spatial learning and memory tasks.  

However, these electrolytic lesions were nonselective and may have also damaged the subcortical inputs to the hippocampus via the fimbria-fornix.  

Others have shown that when normal rodents explored an open field with objects, they detected the displacement of some of the familiar objects within the arena (spatial novelty) and the presence of a new object (object novelty); whereas rodents with hippocampal, fornix, or neonatal selective basal forebrain cholinergic lesions were impaired in detecting spatial, but not object, novelty.  

Adult Long-Evans male rats sustained injections of 5,7-dihydroxytryptamine into the fimbria-fornix (2.5 microg/side) and the cingular bundle (1.5 microg/side) and/or to intraseptal injections of 192 IgG-saporin (0.4 microg/side) in order to deprive the hippocampus of its serotonergic and cholinergic innervations, respectively.  

To test this hypothesis directly, seven rhesus monkeys received a unilateral immunotoxic lesion of the cholinergic cells of the basal forebrain with an ipsilesional section of the fornix. Previous work has shown that monkeys with bilateral section of the anterior temporal stem (white matter of the temporal lobe), amygdala and fornix show a severe new learning impairment, and provide a model of human medial temporal lobe amnesia.  

We investigated the contribution of the NO-cGMP system in the neurotransmission elicited by hippocampal nerve signals which are propagated to the nucleus accumbens via the fornix/fimbria. Basal release of amino acid transmitters was not influenced by NS 2028 and the NO synthase inhibitor, 7-NINA.Electrical stimulation of the fornix/fimbria increased the outflow of aspartate, glutamate and GABA in the nucleus accumbens. UK-114,542 also enhanced the evoked release of glutamate and aspartate while evoked GABA release was not influenced by the phosphodiesterase inhibitor.These findings indicate that NO plays the role of an excitatory transmitter in the nucleus accumbens and that nerve signals from the hippocampus propagated via fornix/fimbria induce NO synthesis in the nucleus accumbens.  

CNTF-immunoreactive astrocytes were exclusively found in white matter structures such as the optical tract, the corticospinal tract, and the fimbria-fornix.  

To determine the importance of fornix and mamillary body atrophy in the secondary generalization of the complex partial seizures fornix and mamillary bodies of 11 hippocampal sclerosis patients with secondary generalization (SG) and 3 without secondary generalization (WSG) were retrospectively evaluated using MRI images. Small fornix and/or mamillary body was not found in WSG group. In SG group the frequencies of small fornix and mamillary body were 64% and 45%, respectively, all being ipsilateral to sclerotic side. The frequency of small fornix in the SG group was statistically higher than WSG group (p<0.01).  

In contrast, lesions of the fornix facilitate acquisition on this task, showing that an intact hippocampal system can interfere with learning an amygdala-dependent task. To the extent that ACh output in the hippocampus reflects activation of that brain area in learning and memory, the results obtained with fornix lesions suggest that ACh release in the hippocampus might be negatively correlated with learning on a CPP task.  

The fimbria-fornix aspiration is a well-known animal model mimicking hippocampal cholinergic deficiency. The aim of the present study was to use in vivo lipid-mediated gene transfer to introduce an expression vector coding for the acetylcholine synthesizing enzyme choline acetyltransferase into the hippocampus to replace the loss of enzyme activity after unilateral fimbria-fornix aspiration. Unilateral fimbria-fornix aspiration led to a marked reduction in the activity of choline acetyltransferase in the hippocampus, which was completely replaced 5 days after lipid-mediated gene transfer of the choline acetyltransferase vector. In conclusion, our data provide evidence that lipid-mediated gene transfer using FuGene is a useful tool to replace loss of choline acetyltranseferase activity in the hippocampus after fimbria-fornix aspiration; however, the lack of good gene transfer efficiency and the transient nature of expression limit its use for clinical applications..  

A comparison of the exploratory behavior of control animals and animals with damage to the fimbria-fornix indicated that the velocity and heading direction of the homeward portion of the trip depends upon the hippocampal formation. While control and fimbria-fornix rats had similar outward segments, the return paths of the fimbria-fornix rats were significantly slower, more circuitous, and more variable compared with that of the control rats.  

Using a radial maze task and different postoperative recovery periods, this experiment assessed and compared the reference and working memory performances of adult Long-Evans male rats subjected to entorhinal cortex, fimbria-fornix, and hippocampus lesions. Conversely, both fimbria-fornix and hippocampus lesions impaired both reference and working memory. While the reference memory deficit was generally similar in both fimbria-fornix and hippocampal lesion groups, analysis of the results for working memory indicated that at the longer delay rats with fimbria-fornix lesions were still impaired but in animals that had the hippocampus removed, working memory did not differ from that of controls. These results suggest that there was some recovery in those rats with hippocampal lesions (e.g., on the working memory task) but both hippocampal and fimbria-fornix animals were still impaired compared to controls when training was delayed 6.5 months following the operations..  

This article reviews 147 cases of amnesia following damage including the hippocampus or fornix as reported in 179 publications. The limited nature of retrograde amnesia following lesions to the fornix is also noted.  

The output signals of CA3 following in the precommissural fornix to the output relay-LS nucleus and to the brain-stem structures have strong regulatory influence on the level of brain activity (arousal), which is an important condition for processing and registration of information. The output signal of CA1-subiculum follows by postcommissural fornix to the chain of structures of the main limbic circuit: mammillary bodies (medial nucleus), anterior thalamic nuclei (mainly antero-ventral nucleus), and cingulate limbic cortex (mainly posterior area).  

This paper reviews studies of object-recognition memory in rats with hippocampal damage produced by ablation, fornix transection, or forebrain ischemia.  

The neural structures involved in cue use and navigational strategies are still poorly understood, although considerable attention is directed toward the contributions of the hippocampal formation (hippocampus and associated pathways and structures, including the fimbria-fornix and the retrosplenial cortex). (1) Control but not fimbria-fornix lesion rats can return to a novel refuge location in both light and dark (infrared) food carrying tasks. Control but not fimbria-fornix lesion rats make periodic direct high velocity returns to a starting location in both light and dark exploratory tests. Control but not fimbria-fornix rats trained in the light to carry food from a fixed location to a refuge are able to maintain accurate outward and homebound trajectories when tested in the dark. Control but not fimbria-fornix rats are able to correct an outward trajectory to a food source when the food source is moved when allothetic cues are present.  

There is now an overwhelming weight of evidence to confirm his four key proposals: that selective destruction of the hippocampus or fornix does not produce dense global amnesia; that the effects of hippocampal or fornix lesions are not primarily a memory impairment, but an impairment in processing spatial information; that damage to the anterior temporal stem is part of the explanation of dense temporal lobe amnesia; and that the interaction of temporal cortex with prefrontal cortex is essential in memory.  

In an attempt to resolve this issue, the present study compared aspiration and cytotoxic ERC lesioned rats, along with fimbria-fornix (FFX) lesioned animals and sham operated controls, on an unsignalled contextual fear conditioning paradigm.  

The present study compared cytotoxic and aspiration ERC lesions with both fimbria fornix (FFX) lesions and sham-operated controls on two spatial learning tasks which have repeatedly been shown to depend on the hippocampus.  

METHOD: Limbic structures (i.e., hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area, fornix, and cingulate, orbitofrontal, and parahippocampal cortices) were traced on 3D T1-weighted MR images of 40 patients with mild to moderate AD and 40 age-, sex-, and education-matched normal control subjects.  

Pyramidal cells (n = 220) were identified by their antidromic activation from the ipsilateral fornix and according to their spike properties.  

Nerve signals from the hippocampus to the nucleus accumbens (NAc) are transmitted through a glutamatergic pathway via the fornix/fimbria fibres. For this purpose, the NAc of urethane-anaesthetized rats was superfused, by the push-pull technique, with compounds that influence the NO system while the fornix/fimbria was electrically stimulated for short periods. Electrical stimulation of the fornix/fimbria increased the ACh output in the NAc. Our findings indicate, that action potentials propagated by the fornix/fimbria to the NAc release glutamate which increases ACh release predominantly via NMDA receptors.  

PURPOSE: We studied the behavioral effects of an intracavitary implantation of poly[ N-(2-hydroxypropyl)-methacrylamidel (PHPMA) hydrogels combined to intraseptal grafts of fetal septal cell suspensions in adult female rats subjected to aspirative fimbria-fornix lesions.  

As ROB has suffered damage to both the fornix and the anterior thalamus, the results of the present study are consistent with the claim that damage to the extended hippocampal system has a much more severe effect on recall than on recognition [ Aggleton JP, Shaw C.  

The length of the corpus callosum was reduced by two-thirds, the fornix commissure was negligible, and the hippocampal volume was reduced by one-third, suggesting a massive disconnection between the cerebral hemispheres and the hippocampi in PDAPP mice.  

This sustained hippocampal inhibitory effect on the adrenocortical response, which was not reported previously, was partially abolished by section of the dorsal fornix. The present data demonstrate that dorsal hippocampal stimulation has a long lasting inhibitory effect on pituitary adrenocortical secretion following neural stimuli and this is partially mediated by the dorsal fornix..  

Degenerating axons were positive for silver staining and were found in the cortex, cingulate cortex, corpus callosum, habenulae, septum, fornix, thalamus, caudate putamen and a few in fasciculus retroflexus and substantia nigra.  

The distribution of cytoplasmic phospholipase A2 (cPLA2), 4-hydroxynonenal (HNE), and choline acetyltransferase (ChAT) was studied in the septum and hippocampus of rats at various time intervals after fimbria-fornix (FF) transection. No increase in cPLA2 or HNE immunoreactivity was observed in neurons of the medial septum after fimbria-fornix transection, even though these showed a decrease in ChAT staining after the lesion. We conclude that there is free-radical damage, as evidenced by HNE formation in neurons of the lateral septum after fimbria-fornix transection, and that this increase in HNE is dependent on phospholipase A2 activity..  

However, a longitudinal neuropsychological evaluation showed a severe deficit in immediate memory and difficulties in planning and consolidation of newly learned information, which may be best related to damage in the frontal basal structures of the brain: the fornix and its connection to the hippocampus and the mamillary bodies.  

In the present study, therefore, we addressed the possible relationship between spatial learning ability and LTP by using rats with bilateral fimbria-fornix lesions.  

The thickness of the posterior column of the fornix and the thickness of the mamillary bodies were also measured. RESULTS: We found 10 cases of ipsolateral hippocampal sclerosis, 6 cases of ipsolateral atrophy of the mamillary body and 4 cases of ipsolateral atrophy of the fornix. CONCLUSION: Hippocampal sclerosis can be associated with lesions of limbic lobe structures (fornix and mamillary body), excluding the cingulate gyrus..  

White and McDonald (Behav Brain Res 1993;55:269-281) demonstrated that amygdala (AMG) lesions impair, while fornix (Fx) lesions enhance learning of this task.  

Changes in the metabolic activity within the brain of patients suffering from Alzheimer's disease (AD) were investigated and compared with biochemical alterations in the hippocampus induced by fimbria/fornix transection in the rat.  

We also found that a small number of cingulate axons project to the septum as well as to the ipsilateral hippocampus via the fornix.  

The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an "extended hippocampal system" comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon.  

We analysed the effects of lesions of hippocampal-diencephalic projections -- fornix (FX) mamillary bodies (MB) and anterior thalamic nuclei (AT) -- and retrohippocampal (RH) lesions including entorhinal cortex and ventral subiculum, upon scene processing.  

We identified 13 published studies in which animals were given equivalent training at two or more separate times before damage to the fornix or hippocampal formation.  

Therefore, the cross-sectional area of the body of the fornix was measured on MR images from 17 young people with schizophrenia, nine with other serious psychiatric illnesses and eight without illness. The mean cross-sectional fornix area in subjects with schizophrenia was significantly larger than that in subjects without illness ( approximately 40%) and psychiatric controls ( approximately 26%). The nature of the larger fornix in early-onset schizophrenia, whether it persists and whether it occurs in schizophrenia presenting in adulthood, remain to be elucidated..  

Wistar rats with hippocampal damage (inflicted by a bilateral lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex, and control-operated rats were examined for their performance in either one of two different spatial tasks in a Morris water maze, a place learning task (requiring a locale system), or a response learning task (requiring a taxon system). Performance of the classical place learning (allocentric) task was found to be impaired in rats with lesions of the fimbria fornix, but not in rats with damage of the medial prefrontal cortex, while the opposite effect was found in the response learning (egocentric) task. When the place learning task was modified by relocating the platform, the impairment in animals with fimbria fornix lesions was even more pronounced than before, while the performance of animals with medial prefrontal cortex lesions was similar to that of their controls. When the task was again modified by changing the hidden platform for a clearly visible one (visual cue task), the animals with fimbria fornix lesions had, at least initially, shorter latencies than their controls.  

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