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PubMed2004

Latent inhibition is spared by N-methyl-D-aspartate (NMDA)-induced ventral hippocampal lesions, but is attenuated following local activation of the ventral hippocampus by intracerebral NMDA infusion.

Repeated non-reinforced exposures of a neutral stimulus retard the development of a conditioned response to that stimulus when it is subsequently paired with a significant event. This stimulus pre-exposure effect is known as latent inhibition (LI). Early lesion studies have initially suggested an important role for the hippocampus in the normal development and expression of LI. This view has since been modified with the emergence of data derived from selective cell body lesions of the hippocampus and of the entorhinal cortex, with an abolition of LI only seen after lesions of the latter. This suggests that the significance of the hippocampus might have been overestimated in the past, possibly due to interruption of fibres en passage. However, intact behavioural expression of LI following hippocampal damage does not preclude the suggestion that the hippocampus participates in the control and regulation of LI expression in intact animals. The present study demonstrated that whilst cell body lesions of the ventral hippocampus spared LI (as expected), chemical activation of the ventral hippocampus by local N-methyl-D-aspartate infusion disrupted LI. These results parallel our earlier observations on prepulse inhibition (PPI) with similar manipulations [Neuroreport 10 (1999) 2533]. Thus, although the ventral hippocampus is itself not responsible for the behavioural manifestation of LI and PPI, it exerts at least a modulatory control over the form and/or magnitude of their expression. Our results should prompt a re-evaluation of the relative roles of the hippocampus and retrohippocampus in the development and expression of LI.

Animals↗

PubMed2005

Age-related changes in brain-derived neurotrophic factor and tyrosine kinase receptor isoforms in the hippocampus and hypothalamus in male rats.

A large amount of aging individuals show diminished cognitive and endocrine capabilities. The main brain areas involved in these changes are the hippocampus and hypothalamus, two regions possessing high plasticity and implicated in cognitive and endocrine functions, respectively. Among neurotrophins (considered as genuine molecular mediators of synaptic plasticity), brain-derived neurotrophic factor (BDNF) exhibits in adult rats, the highest concentrations in the hippocampus and hypothalamus. Most of neuronal effects of BDNF are mediated through high-affinity cell surface BDNF tyrosine kinase receptors (TrkB). Different TrkB isoforms are issued by alternative splicing of mRNA encoding for TrkB (trkB mRNA) generating at least three different TrkB receptors with different signaling capabilities. The goal of this study was to examine simultaneously the expression (mRNAs and proteins) of BDNF and its three specific receptors, in the hippocampus and hypothalamus throughout lifespan in rats. We observed that BDNF essentially increased during the first 2 postnatal weeks in the hippocampus and hypothalamus, with no close correlation to its mRNA levels. In these regions, mRNA encoding for BDNF full-length catalytic receptor (trkB.FL mRNA) showed no important changes throughout life but of the mRNA truncated forms of TrkB receptors (trkB.T1 mRNA and trkB.T2 mRNA) trkB.T1 mRNA strongly increased after birth, then remaining stable during aging. trkB.T2 mRNA gradually decreased from 1 postnatal week becoming undetectable in the hippocampus in old-rats. Proteins issued from these mRNAs showed substantial quantitative modifications with aging. From 2 months old, the BDNF full-length catalytic receptor (TrkB.FL) gradually and significantly decreased in the hippocampus and the hypothalamus. Of the truncated forms of TrkB receptors (TrkB.T1 and TrkB.T2) TrkB.T1, which is essentially localized in glial cells, significantly increased from the first postnatal week in the hippocampus and in the hypothalamus, remaining stable during aging but reduced in old rats. TrkB.T2 which similarly to TrkB.FL has a neuronal localization also gradually decreased in the hippocampus and in the hypothalamus throughout lifespan. These reductions were significant at 21 and 30 days old, respectively. All the changes reported here could contribute to the reduced plasticity of these regions observed in old rats.

Age Factors↗

PubMed2005

Expression of AgRP, NPY, POMC and CART in human fetal and adult hippocampus.

The Agouti-Related Protein (AgRP), Neuropeptide Y (NPY), Proopiomelanocortin (POMC) and the Cocaine and Amphetamine-Regulated Transcript (CART) are four neuropeptides that play essential roles in the regulation of food intake and energy homeostasis in mammals. CART, POMC and NPY have also been suggested to play a role in the development of the hippocampus. We therefore employed quantitative real-time RT-PCR (qPCR) to analyze the expression levels of these genes in the fetal and adult human hippocampus to examine whether the four neuropeptides are differentially regulated in the hippocampus during development. CART (6.5-fold) and POMC (8.3-fold) mRNAs were significantly higher in the adult hippocampus. NPY on the other hand, was significantly reduced (2.1-fold) in the adult hippocampus, while AgRP mRNA was comparatively unchanged between fetal and adult hippocampus. In relative terms, CART mRNA was the highest and AgRP the lowest in both the fetal and adult hippocampus. CART, POMC and NPY are, therefore, differentially expressed in the human fetal and adult hippocampus and could play a role in its development or could be regulated by various stimuli involved in the development of this brain structure.

Aged↗

PubMed2002

M1 muscarinic receptor signaling in mouse hippocampus and cortex.

The five subtypes (M1-M5) of muscarinic acetylcholine receptors signal through G(alpha)(q) or G(alpha)(i)/G(alpha)(o). M1, M3 and M5 receptors couple through G(alpha)(q) and function predominantly as postsynaptic receptors in the central nervous system. M1 and M3 receptors are localized to brain regions involved in cognition, such as hippocampus and cortex, but their relative contribution to function has been difficult to ascertain due to the lack of subtype specific ligands. A functional and genetic approach was used to identify the predominant muscarinic receptor subtype(s) mediating responses in mouse hippocampus and cortex, as well as the relative degree of spare muscarinic receptors in hippocampus. The nonselective muscarinic agonist oxotremorine-M stimulated G(alpha)(q)/11-specific GTP-gamma-35S binding in a concentration dependent manner with a Hill slope near unity in wild type mouse hippocampus and cortex. Muscarinic receptor stimulated G(alpha)(q)/11-specific GTP-gamma-35S binding was virtually abolished in both the hippocampus and cortex of M1 receptor knockout (KO) mice. In contrast, there was no loss of signaling in M3 receptor KO mice in either brain region. Muscarinic receptor reserve in wildtype mouse hippocampus was measured by Furchgott analysis after partial receptor alkylation with propylbenzylcholine mustard. Occupation of just 15% of the M1 receptors in mouse hippocampus was required for maximal efficacy of oxotremorine-M-stimulated GTP-gamma-35S binding indicating a substantial level of spare receptors. These findings support a role for the M1 receptor subtype as the primary G(alpha)(q)/11-coupled muscarinic receptor in mouse hippocampus and cortex.

Animals↗

PubMed2000

Estrogen receptor alpha, but not beta, is expressed in the interneurons of the hippocampus in prepubertal rats: an in situ hybridization study.

Estradiol is involved in the differentiation and plasticity of hippocampal neurons. In the CA1 region, estrogen treatment increases dendritic spines and synapse density on pyramidal cells. In the adult hippocampus, immunoreactivity for estrogen receptor alpha (ERalpha) has been reported in inhibitory interneurons, but neither in the pyramidal neurons nor in granule cells. Estrogens also mediate aspects of sexual differentiation of the hippocampus. To examine the possibility that an alteration in expression of the two types of estrogen receptors (ERalpha and ERbeta) in the hippocampus underlies different roles of estrogen and/or ERs during development and in adult life, we applied non-isotopic, digoxigenin (dig)-labeled, in situ hybridization histochemistry (ISHH) for the both ER forms and examined the distribution pattern of their messages in serial, frontal sections over the postnatal period and in the adult. ERalpha mRNA expression was found scattered throughout the hippocampus especially in the hilar region of the dentate gyrus, and in the strata radiatum and pyramidale in the cornus ammonis at postnatal days (PND) 14, 21 and 35. In the hilus of the dorsal hippocampus, the density of ERalpha-labelled cells was greater in the rostro-medial aspect, while less in the lateral and the caudal region. In the ventral hippocampus the signals for ERalpha mRNA were also found in relatively high density in the hilus. No significant sex difference in distribution and intensity of the ERalpha mRNA positive cells were detected. The hippocampal distribution of ERalpha mRNA expression at PND 14 remained the same on PND 21 and 35 and in adulthood. As reported for adults, ERalpha mRNA signals appear to be in interneurons of the hippocampus but neither in the pyramidal cells nor in the dentate granular cells based on their size and location. In contrast to the result of ERalpha, no clear signals for ERbeta mRNA were detected in the hippocampus across all ages examined, whereas they were clearly detected in the hypothalamus.

Amygdala↗

PubMed1998

Choline availability modulates the expression of TGFbeta1 and cytoskeletal proteins in the hippocampus of developing rat brain.

Choline availability influences long-term memory in concert with changes in the spatial organization and morphology of septal neurons, however little is known concerning the effects of choline on the hippocampus, a region of the brain also important for memory performance. Pregnant rats on gestational day 12 were fed a choline control (CT), choline supplemented (CS), or choline deficient (CD) diet for 6 days and fetal brain slices were prepared on embryonic day 18 (E18). The hippocampus in these brain slices was studied for the immunohistochemical localization of the growth-related proteins transforming growth factor beta type 1 (TGFbeta1) and GAP43, the cytoskeletal proteins vimentin and microtubule associated protein type 1 (MAP1), and the neuronal cell marker neuron specific enolase (NSE). In control hippocampus, there was weak expression of TGFbeta1 and vimentin proteins, but moderately intense expression of MAP1 protein. These proteins were not homogeneously distributed, but were preferentially localized to cells with large cell bodies located in the central (approximately CA1-CA3) region of the hippocampus, and to the filamentous processes of small cells in the fimbria region. Feeding a choline-supplemented diet decreased, whereas a choline-deficient diet increased the intensity of immunohistochemical labeling for these proteins in E18 hippocampus. GAP43 and NSE were localized to peripheral nervous tissue but not hippocampus, indicating that the maturation of axons and neurite outgrowth in embryonic hippocampus were unaffected by the availability of choline in the diet. These data suggest that the availability of choline affects the differentiation of specific regions of developing hippocampus.

Aging↗

PubMed1999

Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver.

An alpha1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of alpha1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90% homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.

Alzheimer Disease↗

PubMed1993

Decreased electroconvulsive shock-induced diacylglycerols and free fatty acid accumulation in the rat brain by Ginkgo biloba extract (EGb 761): selective effect in hippocampus as compared with cerebral cortex.

The effect of Ginkgo biloba extract (EGb 761) treatment (100 mg/kg/day, per os, for 14 days) on electroconvulsive shock (ECS)-induced accumulation of free fatty acids (FFA) and diacylglycerols (DAG) was analyzed in rat cerebral cortex and hippocampus. EGb 761 reduced the FFA pool size by 33% and increased the DAG pool by 36% in the hippocampus. These endogenous lipids were unaffected in cerebral cortex. During the tonic seizure (10 s after ECS) the fast accumulation of FFA, mainly 20:4, was similar in sham- and EGb 761-treated rats, in both the cerebral cortex and hippocampus. However, further accumulation of free 18:0 and 20:4, observed in the hippocampus of sham-treated rats during clonic seizures (30 s to 2 min after ECS), did not occur in EGb 761-treated animals. The rise in DAG content triggered in the cortex and hippocampus by ECS was delayed by EGb 761 treatment from 10 s to 1 min, when values similar to those in sham animals were attained. Moreover, in the hippocampus the size of the total DAG pool was decreased by 19% during the tonic seizure. At later times, DAG content showed a faster decrease in EGb 761-treated rats. By 2 min levels of all DAG acyl groups decreased to values significantly lower than in sham animals in both cortex and hippocampus. This study shows that EGb 761 treatment affects, with high selectivity, lipid metabolism and lipid-derived second messenger release and removal in the hippocampus, while affecting to a lesser extent the cerebral cortex.

Animals↗

PubMed1991

Distribution of protein kinase C in the hippocampus of the gerbil and rat: autoradiographic analysis by [3H]phorbol 12,13-dibutyrate.

In-vitro quantitative receptor autoradiography with [3H]phorbol 12,13-dibutyrate (PDBu) was used to determine the affinity constant (Kd) and the maximum number of receptor sites (Bmax) for protein kinase C (PKC) in subregions of the gerbil hippocampus, and to compare the distribution of [3H]PDBu binding sites in the gerbil hippocampus with that in the rat hippocampus. The Kd and Bmax values in the subregions of the gerbil hippocampus were estimated at 2.6-3.8 nM and 2.38-2.54 pmol (mg tissue)-1, respectively. The distribution of hippocampus [3H]PDBu binding sites was uniform in the gerbil but not in the rat. The [3H]PDBu binding activities in the strata oriens of the CA1 and CA3 subfields and the molecular layer of the dentate gyrus in the rat hippocampus were significantly higher than in the gerbil hippocampus. However, binding activity in the stratum lacunosum-moleculare of the rat CA1 subfield was statistically lower. These data demonstrate a difference in the distribution of [3H]PDBu binding activity in the hippocampus between the gerbil and rat.

Animals↗

PubMedDate not supplied

[Spatial learning and the hippocampus].

INTRODUCTION: Since publication of the book The hippocampus as a cognitive map by O'Keefe and Nadel in 1978, several theoretical and experimental works have supported the participation of the hippocampus in rodents in spatial processing. Since then, great advances have been made into understanding the potential role of the hippocampus in learning and memory processes, relegating a secondary role to the hypothesis that, in rodents, the hippocampus is restricted to the formation of a cognitive map. DEVELOPMENT: In this work, different forms of spatial navigation are analyzed (taxis, cartographic and route integration-based navigation) on a psychological and neurobiological level. The spatial function of the hippocampus proposed by O'Keefe and Nadel is discussed but a more general model is chosen that explains the function of the hippocampus in mammals, i.e. a model of relational memory. Therefore, in the context of relational memory we attempt to explain the different forms of spatial memory in rodents and present the most relevant experimental data that support a critical role for the hippocampus in this kind of memory. CONCLUSIONS: The studies reviewed in this work support an important role for the hippocampus in spatial processing. However, this does not appear to be its sole function and it possibly operates more widely also participating in relational memory.

Animals↗

PubMed2002

Competition between memory systems: acetylcholine release in the hippocampus correlates negatively with good performance on an amygdala-dependent task.

Lesions of the amygdala impair acquisition of a food conditioned place preference (CPP) task. 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. Our recent findings indicate that acetylcholine (ACh) release in the hippocampus increases while rats perform a hippocampus-dependent spontaneous alternation 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. Using in vivo microdialysis, release of ACh was measured in the hippocampus while rats learned and were tested on an amygdala-dependent CPP task and a hippocampus-dependent spontaneous alternation task. Release of ACh in the hippocampus increased when rats were tested on either task. The magnitude of the increase in release of hippocampal ACh was negatively correlated with good performance on the amygdala-dependent CPP task. These findings suggest that ACh release may reflect activation and participation of the hippocampus in learning and memory, but in a manner that can be detrimental to performance on a task dependent on another brain area.

Acetylcholine↗

PubMed1993

Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation and expression.

1. Experiments using localized microinfusions of specific agonists and antagonists of neurotransmitter receptors have shown that the amygdala, hippocampus, medial septum and entorhinal cortex are involved in memory consolidation, storage and expression. The data are consistent with observations derived from lesion studies suggesting a role for these structures in memory processes, but permit many additional conclusions concerning the mechanisms involved and their timing. 2. Memories are initially processed by glutamatergic N-methyl-D-aspartate (NMDA) receptors in amygdala, hippocampus and medial septum, which are sensitive to amino-phosphono valerate (AP5). Memory of inhibitory avoidance is processed by the three structures; memory of habituation to a novel environment is processed only by the hippocampus. At the time of consolidation, immediately after training, gamma-aminobutyrate type A (GABA-A) receptors, modulated by endogenous benzodiazepines, play an inhibitory role, and cholinergic muscarinic and beta-noradrenergic transmission play a modulatory role. 3. From 90 to 180 min after training, memories are blocked by cyano-nitro-quinoxalinedione (CNQX) given into the amygdala, septum and hippocampus. CNQX blocks non-NMDA glutamatergic receptors. Also between 90 and 180 min after training, memory of the habituation and inhibitory avoidance tasks is blocked by the infusion of AP5 or of the GABA-A agonist, muscimol, into the entorhinal cortex. This late post-training intervention of the entorhinal cortex is essential for the integration of successively acquired memories, and occurs in response to the simultaneous activation of CNQX-sensitive synapses in amygdala and hippocampus. 4. The expression of memory is blocked by the infusion of CNQX, at the time of testing, into the amygdala and hippocampus (inhibitory avoidance), into the hippocampus but not the amygdala (habituation), or into the entorhinal cortex (for the two tasks). Since consolidation is blocked by AP5 infused into these structures (see above), the data agree with the hypothesis that memories are mediated by (or actually consist of) long-term potentiation (LTP) in these areas of the brain. LTP induction is blocked by AP5 and LTP expression is blocked by CNQX. It is possible that, at the time of memory expression, the entorhinal cortex is an output of the amygdala and hippocampus.

2-Amino-5-phosphonovalerate↗

PubMedDate not supplied

Delayed decrease of excitatory amino acid neurotransmitters in parietotemporal cortex and hippocampus after complete cerebral ischemia in aged rats.

A 15-min period of complete cerebral ischemia (CCI) was used in aged rats to investigate changes in tissue contents of the amino acid neurotransmitters (AANT) glutamate (glu), aspartate (asp), gamma aminobutyric acid (gaba) and glycine (gly) in parietotemporal cortex and hippocampus during ischemia and up to 96 h of postischemic recirculation. The AANT were determined by HPLC. The excitatory AANT glu and asp showed a first decrease at the end of CCI in hippocampus and after 1 h of postischemic recirculation in parietotemporal cortex, reflecting a release of these AANT into the extracellular space with a further loss into the blood. A second decrease in glu and asp was seen after 24 h of postischemic recirculation in hippocampus and after 48 h in parietotemporal cortex. This coincides with previously described disturbances in energy metabolism from 24 h to 96 h in hippocampus and from 48 h to 72 h in parietotemporal cortex in the same experimental model in aged rats. This might be a causal factor in delayed postischemic neuronal damage. A comparison with investigations in young animals reveals an enhanced decrease of glutamate and aspartate tissue contents during the postischemic recirculation period in old rats indicating an enhanced release of these amino acid neurotransmitters. A significant decrease of gaba tissue content seen in hippocampus at 48 h and 72 h of postischemic recirculation with subsequent disproportion of inhibitory AANT (lower) to excitatory AANT (higher) might reflect a greater vulnerability of hippocampus than of parietotemporal cortex to ischemia. A significant decrease in the NMDA-receptor coactivator gly in parietotemporal cortex at the end of CCI and at 48 h, 72 h, and 96 h of postischemic recirculation, which was not seen in hippocampus, might be another reason for higher vulnerability of hippocampus to ischemia.

Journal Article↗

PubMed1994

The organization of the embryonic and early postnatal murine hippocampus. II. Development of entorhinal, commissural, and septal connections studied with the lipophilic tracer DiI.

We have analyzed the early development of the main hippocampal afferents in the mouse. Following injections of the lipophilic tracer 1-1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in the entorhinal cortex, entorhinal axons were observed for the first time in the hippocampus at E15, in the white matter. At E17, entorhinal fibers arborized within the stratum lacunosum-moleculare. At subsequent stages entorhinal axons formed dense networks that were restricted to their appropriate termination zone in the lacunosum-moleculare. The first axons invading the fascia dentata were noticed at E19, their density increasing at later stages. These axons were mainly present in the outer molecular layer. This onset of entorhinohippocampal projections was corroborated by retrograde labeling data after injections in the hippocampus. Commissural fibers first entered the contralateral hippocampus at E18, their number increasing at the following stages. Commissural axons arborized within the stratum oriens and radiatum in the hippocampus proper. In the fascia dentata, the earliest commissural fibers were seen at P2, terminating in the inner zone of the molecular layer and in the hilus. We conclude that developing entorhinal and commissural axons show a high degree of laminar specificity from the earliest stages of formation, which is compatible with the notion that distinct subsets of early maturing neurons populating the hippocampal plexiform layers may attract particular fiber systems. Hippocamposeptal fibers develop at E15, before the first septal fibers can be detected in the hippocampus. These early hippocamposeptal fibers originated from nonpyramidal neurons and terminated in the medial septal area, which is the main source of septal afferents to the hippocampus. In contrast, septohippocampal fibers were not seen in the hippocampus until E17. At perinatal stages, the hippocamposeptal connection reshapes, sending axons to the dorsolateral septal area as the innervation of the medial septum becomes less conspicuous. This sequence suggests that hippocampal neurons pioneer the formation of septohippocampal connections.

Animals↗

PubMed2004

Ability of GDNF to diminish free radical production leads to protection against kainate-induced excitotoxicity in hippocampus.

The primary aim of this study is to explore the protective mechanisms of glial-derived neurotrophic factor (GDNF) during excitotoxicity by kainate in the hippocampus. After a 15-min microinjection with kainate, excitotoxicity was induced in the rat hippocampus. The protective effect of GDNF in the hippocampus was evaluated by administering GDNF 14 min after injection of kainate. The resulting hydroxyl free radicals were quantified by microdialysis of the hippocampus. The results show that GDNF can effectively suppress the production of kainate-induced hydroxyl free radical production. In addition, histological observation indicated the ability of GDNF to decrease the damage level of pyramidal neurons in the CA3 and CA4 areas of the hippocampus. Superoxide dismutase (SOD) activity in the hippocampus was elevated significantly at 30 min and 7 days after kainate induction, while glutathione peroxidase (cGPx) activity did not increase significantly until the seventh day. With GDNF treatment, SOD and cGPx activity in the hippocampus was elevated significantly 7 days after kainate induction. We suggest that mechanisms including a decrease in free radical generation and scavenging of free radicals might be involved in GDNF protection against kainate-induced excitotoxicity.

Animals↗

PubMed2004

Fos induction and persistence, neurodegeneration, and interneuron activation in the hippocampus of epilepsy-resistant versus epilepsy-prone rats after pilocarpine-induced seizures.

Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.

Animals↗

PubMed2005

Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in mice.

Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl-D-aspartate (NMDA) receptors in the dorsal hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1-45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15-30-s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits.

2-Amino-5-phosphonovalerate↗

PubMed1994

Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers.

A detailed study comparing the distribution of D2 receptors and tyrosine hydroxylase-immunoreactive fibers in the hippocampus and parahippocampal cortices of the rat, cat, and human was conducted. The distribution of [125I]epidepride binding to D2 receptors along the transverse and longitudinal axes of the hippocampus and parahippocampus differed among the species. In rat hippocampus, the number of sites was highest in septal portions of lacunosum-moleculare of CA1 and stratum moleculare of the subiculum. Virtually no binding to D2 receptors existed in the temporal hippocampus. For the cat hippocampus, the highest binding existed in the inner one-third of the molecular layer of the dentate gyrus (DG). There were also significant numbers of D2 receptors in strata radiatum and oriens of the CA subfields, with almost undetectable levels in lacunosum moleculare and subiculum. The number of sites was higher in the septal than temporal hippocampus. In the human hippocampus, highest binding was observed in the molecular layer of DG and the subiculum, with lower levels in strata oriens and lacunosum-moleculare of CA3, and very low binding in CA1. The histochemical demonstration of the pattern of mossy fibers revealed an organization complementary to that of D2 receptors in cat and human. In none of the species was there significant expression of D2 receptors in the entorhinal cortex, except in the caudal extreme of this region in the rat. In that region a trilaminar pattern was exhibited that continued into the perirhinal cortex. A trilaminar pattern of D2 receptor expression was observed in the perirhinal cortex of all species, with the highest values in the external and deep laminae and low expression in the middle laminae. The organization of dopamine fibers was assessed by comparing the distribution of tyrosine hydroxylase-positive and dopamine beta-hydroxylase-immunoreactive fibers in these same regions. It revealed consistent mismatches between the pattern of D2 receptor expression and dopaminergic innervation in all three species. The implications for this mismatch are discussed. It is hypothesized that the distribution of D2 receptors, and not of dopamine fibers, determines what neural systems dopamine influences in the hippocampal complex.

Aged↗