Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HIPPOCAMPUS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus.

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.

Amygdala↗

Longitudinal axis of the hippocampus: both septal and temporal poles of the hippocampus support water maze spatial learning depending on the training protocol.

It has been suggested previously that 30% sparing of the hippocampus is enough to support spatial learning of a reference memory task in a water maze provided the spared tissue is located septally (Moser et al. 1995, Proc Natl Acad Sci USA 92:9697-9701). Therefore, the temporal hippocampus may not be involved in spatial memory. Place cells are also found in this part of the structure, and it has been suggested that these place cells have larger, less well-tuned place fields than are found in the septal hippocampus. We tested the possibility that the temporal hippocampus might be involved in spatial learning when the animals are required to distinguish between different contexts. Experiment 1 was a replication of the findings reported by Moser et al., using their protocol (8 trials/day, 6 days) and the groups with 20-40% hippocampus spared septally or temporally (volume assessed by quantitative volumetric techniques). In experiment 2, rats with also 20-40% sparing of the hippocampus either septally or temporally were trained in two water maze concurrently (four trials/day/water maze, 8 days). Rats with 20-40% hippocampus spared temporally were able to learn the two water maze tasks normally, and no difference was observed between rats with septal and temporal hippocampus spared across different measures of performance. In experiment 3, rats with 20-40% hippocampus spared septally or temporally were trained in one water maze as in experiment 1, but using a spaced training protocol similar to that of experiment 2 (four trials/day, 8 days). Rats with temporal hippocampus spared developed a preference for the training quadrant and acquired levels of performance indistinguishable from those of rats with septal hippocampus spared. The results suggest that the temporal hippocampus can support the learning of two, but also one, spatial water maze reference memory task, provided the training protocol is adequate.

Animals↗

Is the avian hippocampus a functional homologue of the mammalian hippocampus?

The effects of hippocampal lesions on the processing and retention of visual and spatial information in birds and mammals is reviewed. Both birds and mammals with damage to the hippocampus are severely impaired on a variety of spatial tasks, such as navigation, maze learning, and the retention of spatial information. In contrast, both birds and mammals with damage to the hippocampus are not impaired on a variety of visual tasks, such as delayed matching-to-sample, concurrent discrimination, or retention of a visual discrimination. In addition, both birds and mammals with hippocampal damage display impairments in the acquisition of an autoshaped response, as well as alterations in response suppression. These findings suggest that the avian hippocampus is a functional homologue of the mammalian hippocampus, and that in both birds and mammals the hippocampus is important for the processing and retention of spatial, rather than purely visual information.

Animals↗

Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory.

CREB is critical for long-lasting synaptic and behavioral plasticity in invertebrates. Its role in the mammalian hippocampus is less clear. We have interfered with CREB family transcription factors in region CA1 of the dorsal hippocampus. This impairs learning in the Morris water maze, which specifically requires the dorsal hippocampus, but not context conditioning, which does not. The deficit is specific to long-term memory, as shown in an object recognition task. Several forms of late-phase LTP are normal, but forskolin-induced and dopamine-regulated potentiation are disrupted. These experiments represent the first targeting of the dorsal hippocampus in genetically modified mice and confirm a role for CREB in hippocampus-dependent learning. Nevertheless, they suggest that some experimental forms of plasticity bypass the requirement for CREB.

Activating Transcription Factor 1↗

Hippocampus as comparator: role of the two input and two output systems of the hippocampus in selection and registration of information.

Processing of multimodal sensory information by the morphological subdivisions of the hippocampus and its input and output structures was investigated in unanesthetized rabbits by extracellular recording of neuronal activity. Analysis shows principal differences between CA3 neurons with uniform multimodal, mainly inhibitory, rapidly habituating sensory responses, and CA1-subicular neurons, substantial parts of which have phasic reactions and patterned on-responses, depending on the characteristics of the stimuli. These differences result from the organization of the afferent inputs to CA1 and CA3. Analysis of neuronal responses in sources of hippocampal inputs, their electrical stimulation, and chronic disconnection show the greater functional significance of the brain-stem reticular input for tonic responses characteristic of CA3. This input signal before entering the hippocampus is additionally preprocessed at the MS-DB relay, where it becomes more uniform and frequency-modulated in the range of theta-rhythm. It is shown that the new sensory stimuli produce inhibitory reset, after which synchronized theta-modulation is triggered. Other stimuli, appearing at the background of the ongoing theta, do not evoke any responses of the hippocampal neurons. Thus, theta-modulation can be regarded as a mechanism of attention, which prolongs response to a selected stimulus and simultaneously protects its processing against interference. The cortical input of the hippocampus introduces highly differentiated information analyzed at the highest levels of the neocortex through the intermediary of the entorhinal cortex and presubiculum. However, only CA1-subiculum receives this information directly; before its entrance into CA3, it is additionally preprocessed at the FD relay, where the secondary simplification of signals occurs. As a result, CA3 receives by its two inputs (MS-DB and FD) messages just about the presence and level of input signals in each of them, and performs relatively simple functions of determination of match/mismatch of their weights. For this comparator system, the presence of signal only in the reticulo-septal input is equivalent to quality of novelty. The cortical signal appears with some delay, after its analysis in the neocortex and shaping in the prehippocampal structures; besides, it is gradually increased due to LTP-like incremental changes in PP and mossy fiber synapses. The CA3 neurons with potentiated synapses of cortical input do not respond to sensory stimuli; that is, the increased efficacy of the cortical signals can be regarded as "familiarity" of a signal, terminating the reactive state of the CA3 neurons. The integrity of both inputs is necessary for gradual habituation of sensory responses in the hippocampus. 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 primary targets of this output signal are raphe nuclei, which suppress activity of the ascending excitatory RF. In the background state, activity of the CA3 neurons through the intermediary of raphe keeps RF under tonic inhibitory control. Inhibition of the majority of CA3 pyramidal neurons during a novel stimulus action decreases the volume of its output signal to raphe and releases RF from tonic inhibition (increase in level of activity of the forebrain, arousal). When the responses of CA3 neurons habituate, the initial high background activity is reinstated, as well as tonic suppression of RF. Analysis of the second output of CA3 (by Schaffer's collaterals to CA1) shows that activity in this pathway can block access of cortical signals from PP to CA1 neurons by action upon the local system of inhibitory neurons, or by shunting the propagation of signals in apical dendrites. Thus, CA3 can act as a filter controlling the information transmission by CA1; such transmission at any given moment is allowed only in those CA1 neurons which receive SC from CA3 neurons, responding to the sensory stimulus by suppression of their activity. Disconnection of the CA3 output fibers results in disappearance of habituation in all its target structures (raphe, RF, CA1). 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). In each of these links, the signal is additionally processed. Habituation is nearly absent in these structures; instead, st

Animals↗

[Histochemical and biochemical investigations of the hippocampus and neocortex of the wistar rat. III. Electron-microscopic investigations on the localization of non-specific esterases in the hippocampus (author's transl)].

This report describes the ultrastructural localization of the non-specific esterases in the pyramidal cells of the CA3-region of rat hippocampus. The use of specific inhibitors allowed the differentiation between aryl-, carboxyl- and acetylesterases. The thiolacetic acid reaction at pH = 5.2 and 7.0 proved to be a favourable method for the conditions of the hippocampus. Liver tissue served for control purposes. In the pyramidal cells carboxylesterase could be demonstrated on membranes and cisternes of the endoplasmic reticulum on polysomes and in the nuclear envelope. Arylesterase was localized in numerous synaptic vesicles and in the myeline sheath of axons. In lysosomes and in mitochondria an esterase activity was demonstrable, which behaved like an acetylesterase. In the hippocampus carboxylesterase could be shown only at pH = 7.0, whereas in liver this enzyme also give a clear reaction at pH = 5.2. Aryl- and acetylesterase reacted at both pH-ranges in the hippocampus. Biochemical investigations showed that the tissue pretreatment, which is necessary for the ultrahistochemical demonstration of nonspecific esterases considerable decreased the enzyme activity. Formaldehyde and glutaraldehyde have thereby a different action on the several esterase types.

Animals↗

Autoradiographic localization of opioid and spirodecanone receptors in the gerbil hippocampus as compared with the rat hippocampus.

Opioid ([3H]naloxone) and spirodecanone ([3H]spiperone) binding sites in the hippocampus were visualized in the Mongolian gerbil and in the rat using in vitro autoradiography. In the hippocampus, marked differences were noted in the stratum (sr.) pyramidale of the CA1 subfield where opioid and spirodecanone (assayed in the presence of mianserin and sulpiride) binding activities were very low in gerbils, but high in rats. Gerbils exhibited a high concentration of [3H]naloxone binding sites in the sr. pyramidale of the CA3 subfield, as observed in the rat. In addition, the gerbil has a very high opioid receptor density in the hilar region and in the sr. moleculare of the dentate gyrus. The cellular localization of opioid and spirodecanone receptor sites was studied in the rat hippocampus using selective neuronal damage to CA1 and CA3 neurons by means of ischemia and kainic acid treatment, respectively. The results suggest that the gerbil differs from the rat with respect to the characteristic pyramidal cells (spirodecanone binding site) and interneurons (opioid receptor) in the CA1 subfield of the hippocampus. Distinct localization of opioid and spirodecanone receptors in the gerbil provides a good model with which to investigate the electrophysiological and biochemical roles of opioid peptides and butyrophenone spirodecanone drugs.

Animals↗

Median raphe- and contralateral hippocampus-elicited EEG spikes which correspond to hyperpolarizations of pyramidal cells in the kindled hippocampus of the rabbit.

Rabbit hippocampus was chronically stimulated with implanted electrodes until interictal EEG spikes were kindled in it. The kindled hippocampus was then studied in acute experiments. Stimulation of the median raphe nucleus and that of the opposite hippocampus produced EEG spikes, whose intracellular correlates were hyperpolarizations of pyramidal cells (referred to as inhibitory EEG spikes).

Animals↗

Neurohypophysial peptides and the hippocampus. I. Vasopressin immunoreactivity in the rat hippocampus.

Immunocytochemical studies have demonstrated that nerve fibres containing immunoreactive vasopressin project to many areas of the central nervous system. In the present investigation, the presence of immunoreactive arginine vasopressin (IR-AVP) in the hippocampus of Wistar rats was confirmed by radioimmunoassay. The vasopressin content of the dorsal hippocampus was 30.3 +/- 7.3 pg IR-AVP/mg soluble protein (mean +/- SEM, n = 9) and that of the ventral hippocampus was 81.4 +/- 8.3 pg IR-AVP/mg soluble protein (n = 9), while tissue from the cerebral cortex contained no detectable vasopressin. That the immunoreactivity was due to vasopressin was confirmed by its absence in hippocampal or cortical tissue from homozygous Brattleboro rats, which are genetically unable to synthesize vasopressin.

Animals↗

Lesions of the ventral hippocampus, but not the dorsal hippocampus, impair conditioned fear expression and inhibitory avoidance on the elevated T-maze.

The hippocampus has been suggested to be involved in spatial (or configural) memory and also in the inhibition of certain response or goal alternatives. An increasing number of anatomical, physiological, and behavioral studies indicate that the hippocampus is functionally heterogeneous along the dorsal-ventral axis. Identification of distinct behavioral roles for the dorsal (DH) and ventral (VH) hippocampus may resolve differences between the various theoretical accounts of hippocampal function. The present study examined the effects of electrolytic lesions restricted to the DH or VH on fear-conditioned freezing, passive avoidance on the elevated T-maze (ETM) test of anxiety, and general activity in male Sprague-Dawley (Charles-River derived) albino rats. We found that rats with lesions of the VH, but not DH showed reduced freezing to both context and tone conditioned stimuli (CS). Rats with VH lesions also showed a reduced latency to emerge from the enclosed arm on trials 2 and 3 of the ETM (indicating reduced anxious behavior), while having no effect on the latency to escape from the open arms on trial 4. There were no differences in activity between the groups. These results indicate that the VH and DH are differentially involved in passive avoidance on the ETM and conditioned freezing to context and tone CS. We suggest that the VH may be specifically involved in modulating goal-oriented, defensive behavior expression through hypothalamic and amygdaloid connections.

Acoustic Stimulation↗

Differential effects of centrally-active antihypertensives on 5-HT1A receptors in rat dorso-lateral septum, rat hippocampus and guinea-pig hippocampus.

1. The electrophysiological responses elicited by 5-hydroxytryptamine1A-(5-HT1A) receptor agonists in rat and guinea-pig CA1 pyramidal neurones and rat dorso-lateral septal neurones were compared in vitro by use of conventional intracellular recording techniques. 2. In the presence of 1 microM tetrodotoxin (TTX), to prevent indirect effects, 5-HT, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) hyperpolarized the neurones from rat and guinea-pig brain. 3. The hypotensive drug flesinoxan, a selective 5-HT1A receptor agonist, hyperpolarized neurones in all three areas tested; however, another hypotensive agent with high affinity at 5-HT1A-receptors, 5-methyl-urapidil, hyperpolarized only the neurones in rat hippocampus and septum. 4. In guinea-pig hippocampal neurones, 5-methyl-urapidil behaved as a 5-HT1A-receptor antagonist. 5. The relative efficacies (5-HT = 1) of DP-5-CT, 8-OH-DPAT, flesinoxan and 5-methyl-urapidil at the three sites were: rat hippocampus, 1.09, 0.7, 0.5 and 0.24; rat septum, 0.88, 0.69, 0.82 and 0.7; guinea-pig hippocampus, 1.0, 0.69, 0.89 and 0, respectively. 6. It is concluded that the hypotensive agents flesinoxan and 5-methyl-urapidil appear to have different efficacies at 5-HT1A receptors located in different regions of the rodent brain. Whether these regional and species differences arise from receptor plurality or variability in intracellular transduction mechanisms remains to be elucidated.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Priming of long-term potentiation in mouse hippocampus by corticotropin-releasing factor and acute stress: implications for hippocampus-dependent learning.

In the present experiments, we characterized the action of human/rat corticotropin-releasing factor (h/rCRF) and acute stress (1 hr of immobilization) on hippocampus-dependent learning and on synaptic plasticity in the mouse hippocampus. We first showed that h/rCRF application and acute stress facilitated (primed) long-term potentiation of population spikes (PS-LTP) in the mouse hippocampus and enhanced context-dependent fear conditioning. Both the priming of PS-LTP and the improvement of context-dependent fear conditioning were prevented by the CRF receptor antagonist [Glu(11,16)]astressin. PS-LTP priming and improved learning were also reduced by the protein kinase C inhibitor bisindolylmaleimide I. Acute stress induced the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) 2 hr after the end of the stress session. The CaMKII inhibitor KN-62 antagonized the stress-mediated learning enhancement, however, with no effect on PS-LTP persistence. Thus, long-lasting increased neuronal excitability as reflected in PS-LTP priming appeared to be essential for the enhancement of learning in view of the observation that inhibition of PS-LTP priming was associated with impaired learning. Conversely, it was demonstrated that inhibition of CaMKII activity reduced contextual fear conditioning without affecting PS-LTP priming. This observation suggests that priming of PS-LTP and activation of CaMKII represent two essential mechanisms that may contribute independently to long-term memory.

Action Potentials↗

The distribution of [3H]kainate binding sites in primate hippocampus is similar to the distribution of both Ca2+-sensitive and Ca2+-insensitive [3H]kainate binding sites in rat hippocampus.

The distribution of [3H]kainate binding sites was determined by quantitative autoradiography in three vertebrate species: rat, monkey, and human. These animals displayed a similar pattern of binding site density in the hippocampus. Highest levels were found within the stratum lucidum and moderate levels in the inner portion of the dentate gyrus molecular layer. Although the distribution is similar, there is a lower density of binding sites in the stratum lucidum of primates than in rodents. Experiments using rat brain synaptic plasma membrane fractions indicated that inclusion of Ca2+ ions results in a selective reduction in binding at the high affinity sites. The Ca2+-inhibited and Ca2+-inhibited binding sites in the high affinity sites. The Ca2+ -inhibited and Ca2+ -insensitive binding sites in the rat hippocampus exhibited a similar distribution. Together, these results suggest that in a variety of mammalian species kainate receptors exhibit similar regional distributions, and that the high and low affinity kainate binding sites also exhibit similar regional distributions.

Autoradiography↗

Hippocampus and Pavlovian fear conditioning in rats: muscimol infusions into the ventral, but not dorsal, hippocampus impair the acquisition of conditional freezing to an auditory conditional stimulus.

The authors compared the effects of pharmacological inactivation of the dorsal hippocampus (DH) or ventral hippocampus (VH) on Pavlovian fear conditioning in rats. Freezing behavior served as the measure of fear. Pretraining infusions of muscimol, a GABAA receptor agonist, into the VH disrupted auditory, but not contextual, fear conditioning; DH infusions did not affect fear conditioning. Pretesting inactivation of the VH or DH did not affect the expression of conditional freezing. Pretraining electrolytic lesions of the VH reproduced the effects of muscimol infusions, whereas posttraining VH lesions disrupted both auditory and contextual freezing. Hence, neurons in the VH are importantly involved in the acquisition of auditory fear conditioning and the expression of auditory and contextual fear under some conditions.

Acoustic Stimulation↗

The ventral hippocampus supports a memory representation of context and contextual fear conditioning: implications for a unitary function of the hippocampus.

The authors report that either inactivating the ventral hippocampus (VH) with muscimol prior to context preexposure or injecting anisomycin into the VH after preexposure significantly impaired rats' memory for context. Injecting anisomycin into the VH prior to contextual fear conditioning also greatly reduced long-term memory (48-hr retention test) but had no effect on short-term memory (1-hr retention test) for contextual fear. Together with other results, these data suggest that the memory for a novel context is distributed throughout the longitudinal extent of the hippocampus and that this representation helps to support contextual fear conditioning.

Animals↗

Gene expression in the forebrain of dexamethasone-treated pigs: effects on stress neuropeptides in the hypothalamus and hippocampus and glutamate receptor subunits in the hippocampus.

Gene expression studies advance our understanding of the effects of stress and glucocorticoids on brain function and give a new direction to animal welfare research. In this context, the presence of messenger RNA s (m RNA s) for corticotrophin releasing hormone (CRH) and vasopressin (VP) in the porcine hypothalamus has recently been documented. This study investigated the expression of CRH, VP and ionotropic glutamate receptor (iGluR) subunit m RNA s in the brains of pigs treated with the synthetic glucocorticoid dexamethasone (Dex; 5 mg kg(-1)i.v.). In the hypothalamus, VP, but not CRH, m RNA was reduced 3 hours after Dex. In the hippocampus, expression of m RNA s for some iGluR subunits appeared to be differentially regulated 6 hours after Dex. In addition, CRH message was detected in the hippocampus and significantly upregulated in the CA1 region 3 hours after Dex. The relevance of these findings to stress neurobiology of the growing pig is discussed.

Animals↗

Hippocampus-dependent retrieval and hippocampus-independent extinction of place avoidance navigation, and stress-induced out-of-context activation of a memory revealed by reversible lesion experiments in rats.

The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bures and Olga Buresova. We use the occasion of Jan's 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats.

Animals↗

Place navigation in rats with unilateral tetrodotoxin inactivation of the dorsal hippocampus: place but not procedural learning can be lateralized to one hippocampus.

Lateralization of the Morris water maze task was examined by injecting 5 ng of tetrodotoxin (TTX) into one dorsal hippocampus (HPC) of chronically cannulated rats (n = 20). The task, acquired (A) during unilateral HPC block, was retrieved (R) during TTX blockade of the ipsi- (I) or contralateral (C) HPC. Escape latencies (in seconds) at 3 levels of acquisition and in the first 4-trial block of I or C retrieval suggest lateralization was absent after the first block (A = 49, I = 40, C = 44), partial after training to an efficient search strategy (A = 6, I = 9, C = 14), and complete after overtraining to goal-directed escape (A = 4, I = 4, C = 12), as further indicated by comparisons of A vs. R behavior and probe trials. The analyses also indicate that (a) HPC contributes to the acquisition but is unnecessary for retrieval of the procedural engram, (b) overtrained learning with one HPC or intact brain is similar, and (c) there is no left-right hemispheric specialization for place learning.

Animals↗