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Hippocampus
Kinds of Hippocampus Selected AbstractsPropagation Dynamics of Epileptiform Activity Acutely Induced by Bicuculline in the Hippocampal,Parahippocampal Region of the Isolated Guinea Pig BrainEPILEPSIA, Issue 12 2005Laura Uva Summary:,Purpose: Aim of the study is to investigate the involvement of parahippocampal subregions in the generation and in the propagation of focal epileptiform discharges in an acute model of seizure generation in the temporal lobe induced by arterial application of bicuculline in the in vitro isolated guinea pig brain preparation. Methods: Electrophysiological recordings were simultaneously performed with single electrodes and multichannel silicon probes in the entorhinal, perirhinal, and piriform cortices and in the area CA1 of the hippocampus of the in vitro isolated guinea pig brain. Interictal and ictal epileptiform discharges restricted to the temporal region were induced by a brief (3,5 min) arterial perfusion of the GABAA receptor antagonist, bicuculline methiodide (50 ,M). Current source density analysis of laminar field profiles performed with the silicon probes was carried out at different sites to establish network interactions responsible for the generation of epileptiform potentials. Nonlinear regression analysis was conducted on extracellular recordings during ictal onset in order to quantify the degree of interaction between fast activities generated at different sites, as well as time delays. Results: Experiments were performed in 31 isolated guinea pig brains. Bicuculline-induced interictal and ictal epileptiform activities that showed variability of spatial propagation and time course in the olfactory,temporal region. The most commonly observed pattern (n = 23) was characterized by the initial appearance of interictal spikes (ISs) in the piriform cortex (PC), which propagated to the lateral entorhinal region. Independent and asynchronous preictal spikes originated in the entorhinal cortex (EC)/hippocampus and progressed into ictal fast discharges (around 25 Hz) restricted to the entorhinal/hippocampal region. The local generation of fast activity was verified and confirmed both by CSD and phase shift analysis performed on laminar profiles. Fast activity was followed by synchronous afterdischarges that propagated to the perirhinal cortex (PRC) (but not to the PC). Within 1,9 min, the ictal discharge ceased and a postictal period of depression occurred, after which periodic ISs in the PC resumed. Unlike preictal ISs, postictal ISs propagated to the PRC. Conclusions: Several studies proposed that reciprocal connections between the entorhinal and the PRC are under a very efficient inhibitory control (1). We report that ISs determined by acute bicuculline treatment in the isolated guinea pig brain progress from the PC to the hippocampus/EC just before ictal onset. Ictal discharges are characterized by a peculiar pattern of fast activity that originates from the entorhinal/hippocampal region and only secondarily propagates to the PRC. Postictal propagation of ISs to the PRC occured exclusively when an ictal discharge was generated in the hippocampal/entorhinal region. The results suggest that reiteration of ictal events may promote changes in propagation pattern of epileptiform discharges that could act as trigger elements in the development of temporal lobe epilepsy. [source] MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Sheng-Li Sun SUMMARY 1Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis. 2The present study used middle cerebral artery occlusion (MCAO) to induce ischaemia and reperfusion in Sprague-Dawley rats. Using superarray Q series Janus tyrosine kinases (Jak)/STAT signalling pathway gene array, a total of 96 genes was screened in adult male rat hippocampus after transient focal cerebral ischaemia. 3The results showed that 23 genes were upregulated at least twofold by ischaemia treatment and that 12 genes were downregulated at least threefold by ischaemia treatment compared with controls. 4After confirmation by quantitative real-time polymerase chain reaction, the data suggest that the gene expression of STAT2, 5a, 5b, 6 and suppressor of cytokine signalling (SOCS) 4 was increased by ischaemia, probably due to a compensatory response of the brain, which may play a protective role in damaged brain tissue. 5The results of the present study provide evidence on global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion, in which STAT2, 5a, 5b, 6 and SOCS4 were confirmed to be significantly modulated during focal cerebral ischaemia. [source] Effect of Interictal Spikes on Single-Cell Firing Patterns in the HippocampusEPILEPSIA, Issue 4 2007Jun-Li Zhou Summary:,Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. Methods: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. Results: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. [source] Effects of Potassium Concentration on Firing Patterns of Low-Calcium Epileptiform Activity in Anesthetized Rat Hippocampus: Inducing of Persistent Spike ActivityEPILEPSIA, Issue 4 2006Zhouyan Feng Summary:,Purpose: It has been shown that a low-calcium high-potassium solution can generate ictal-like epileptiform activity in vitro and in vivo. Moreover, during status epileptiform activity, the concentration of [K+]o increases, and the concentration of [Ca2+]o decreases in brain tissue. Therefore we tested the hypothesis that long-lasting persistent spike activity, similar to one of the patterns of status epilepticus, could be generated by a high-potassium, low-calcium solution in the hippocampus in vivo. Methods: Artificial cerebrospinal fluid was perfused over the surface of the exposed left dorsal hippocampus of anesthetized rats. A stimulating electrode and a recording probe were placed in the CA1 region. Results: By elevating K+ concentration from 6 to 12 mM in the perfusate solution, the typical firing pattern of low-calcium ictal bursts was transformed into persistent spike activity in the CA1 region with synaptic transmission being suppressed by calcium chelator EGTA. The activity was characterized by double spikes repeated at a frequency ,4 Hz that could last for >1 h. The analysis of multiple unit activity showed that both elevating [K+]o and lowering [Ca2+]o decreased the inhibition period after the response of paired-pulse stimulation, indicating a suppression of the after-hyperpolarization (AHP) activity. Conclusions: These results suggest that persistent status epilepticus,like spike activity can be induced by nonsynaptic mechanisms when synaptic transmission is blocked. The unique double-spike pattern of this activity is presumably caused by higher K+ concentration augmenting the frequency of typical low-calcium nonsynaptic burst activity. [source] Epileptiform Activity Induced by Pharmacologic Reduction of M-Current in the Developing Hippocampus in VitroEPILEPSIA, Issue 1 2006Fernando Peña Summary:,Purpose: Benign familial neonatal convulsions (BFNCs), an inheritable epilepsy that occurs in neonates but not in adults, is caused by hypofunctional mutations in genes codifying for the M-type K+ current. In an attempt to develop an in vitro model of this disease, we tested whether blocking M-current with linopirdine induces epileptiform activity in brain slices from animals of different ages. Methods: Horizontal hippocampus,entorhinal cortex slices were obtained from neonatal (1,2 weeks after birth) and adult (8,9 weeks after birth) rats. Extracellular field recordings of the CA1 region were performed. After recording control conditions, linopirdine was added to the bath, and field activity was recorded continuously for 3 h. 4-Aminopyridine, a drug commonly used to induce epileptiform activity in vitro, was used as a control for our experimental conditions. Results: Bath perfusion of linopirdine induced epileptiform activity only in slices from neonatal rats. Epileptiform activity consisted of interictal-like and ictal-like activity. In slices from adult rats, linopirdine induced erratic interictal-like activity. In contrast, 4-aminopyridine was able to induce epileptiform activity in slices from both neonatal and adult rats. Conclusions: We demonstrated that blockade of M-current in vitro produces epileptiform activity with a developmental pattern similar to that observed in BNFCs. This could be an in vitro model that can be used to study the cellular mechanisms of epileptogenesis and the developmental features of BFNCs, as well as to develop some therapeutic strategies. [source] The role of the medial caudate nucleus, but not the hippocampus, in a matching-to sample task for a motor responseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Raymond P. Kesner Abstract A delayed-match-to-sample task was used to assess memory for motor responses in rats with control, hippocampus, or medial caudate nucleus (MCN) lesions. All testing was conducted on a cheeseboard maze in complete darkness using an infrared camera. A start box was positioned in the centre of the maze facing a randomly determined direction on each trial. On the sample phase, a phosphorescent object was randomly positioned to cover a baited food well in one of five equally spaced positions around the circumference of the maze forming a 180-degree arc 60 cm from the box. The rat had to displace the object to receive food and return to the start box. The box was then rotated to face a different direction. An identical baited phosphorescent object was placed in the same position relative to the start box. A second identical object was positioned to cover a different unbaited well. On the choice phase, the rat must remember the motor response made on the sample phase and make the same motor response on the choice phase to receive a reward. Hippocampus lesioned and control rats improved as a function of increased angle separation used to separate the correct object from the foil (45, 90, 135, and 180 degrees) and matched the performance of controls. However, rats with MCN lesions were impaired across all separations. Results suggest that the MCN, but not the hippocampus, supports working memory and/or a process aimed at reducing interference for motor response selection based on vector angle information. [source] Dose-dependent long-term effects of Tat in the rat hippocampal formation: A design-based stereological studyHIPPOCAMPUS, Issue 4 2010Sylvia Fitting Abstract The human immunodeficiency virus type 1 (HIV-1) protein transactivator of transcription (Tat) is believed to play a critical role in mediating central nervous system (CNS) pathology in pediatric HIV-1 infection. Long-term neurotoxicity was investigated in a design-based stereology study following intrahippocampal injection of Tat on postnatal day (P)10, a time period that approximates the peak in the rats' rate of brain growth and mimics clinical HIV-1 CNS infection at labor/delivery. The goal was to examine the impact of P10 intrahippocampal Tat injection on the anatomy of the adult hippocampus (5 month) to gain a better understanding about how timing of infection influences the rate of progression of pediatric HIV-1 infection [cf. Fitting et al. (2008a) Hippocampus 18:135,147]. Male P10 Sprague-Dawley rats were bilaterally injected with vehicle or one of three different doses of Tat (5, 25, or 50 ,g). Unbiased stereological estimates were used to quantify total neuron number (Nissl stain) in five major subregions of the rat hippocampus: granular layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB). Glial cells (astrocytes and oligodendrocytes) were quantified in the DGH and SUB. No significant reduction of neuron number was noted for any of the five hippocampal subregions, in contrast to the very prominent reductions reported when Tat was administered on P1 [Fitting et al. (2008a) Hippocampus 18:135,147]. However, for glial cells, the number of astrocytes in the DGH and SUB as well as the number of oligodendrocytes in the DGH were linear dose dependently increased as a function of dose of Tat. In conjunction with previous stereological research [Fitting et al., (2008a) Hippocampus 18:135,147], the present data suggest that variability in the progression of pediatric HIV/acquired immunodeficiency syndrome (AIDS) may be better understood with the knowledge of the factor of timing of HIV-1 CNS infection. © 2009 Wiley-Liss, Inc. [source] Hippocampus modulates the behaviorally-sensitizing effects of nicotine in a rat model of novelty-seeking: Potential role for mossy fibersHIPPOCAMPUS, Issue 10 2007Amrinder S. Bhatti Abstract Present experiments investigate interactions between a rat model of the novelty-seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally-sensitizing effects of NIC. Outbred rats were phenotype-screened as high-responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low-responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3-d intervals on postnatal days 33,44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra-pyramidal mossy fiber (SP-MF) terminal field. The increase in the SP-MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC-induced locomotion and the SP-MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC. © 2007 Wiley-Liss, Inc. [source] Hippocampus and its interactions within the medial temporal lobeHIPPOCAMPUS, Issue 9 2007Kathryn J. JefferyArticle first published online: 2 JUL 200 First page of article [source] Learning in a geometric model of place cell firingHIPPOCAMPUS, Issue 9 2007Caswell Barry Abstract Following Hartley et al. (Hartley et al. (2000) Hippocampus 10:369,379), we present a simple feed-forward model of place cell (PC) firing predicated on neocortical information regarding the environmental geometry surrounding the animal. Incorporating the idea of boundaries with distinct sensory qualities, we show that synaptic plasticity mediated by a BCM-like rule (Bienenstock et al. (1982) J Neurosci 2:32,48) produces PCs that encode position relative to specific extended landmarks. In an unchanging environment the model is shown to undergo an initial phase of learning, resulting in the formation of stable place fields. In familiar environments, perturbation of environmental cues produces graded changes in the firing rate and position of place fields. Model simulations are compared favorably with three sets of experimental data: (1) Results published by Barry et al. (Barry et al. (2006) Rev Neurosci 17:71,97) showing the slow disappearance of duplicate place fields produced when a barrier is placed into a familiar environment. (2) Rivard et al.'s (Rivard et al. (2004) J Gen Physiol 124:9,25) study showing a graded response in PC firing such that fields near to a centrally placed object encode space relative to the object, whereas more distant fields respond to the surrounding environment. (3) Fenton et al.'s (Fenton et al. (2000a) J Gen Physiol 116:191,209) observation that inconsistent rotation of cue cards produces parametric changes in place field positions. The merits of the model are discussed in terms of its extensibility and biological plausibility. © 2007 Wiley-Liss, Inc. [source] An oscillatory interference model of grid cell firingHIPPOCAMPUS, Issue 9 2007Neil Burgess Abstract We expand upon our proposal that the oscillatory interference mechanism proposed for the phase precession effect in place cells underlies the grid-like firing pattern of dorsomedial entorhinal grid cells (O'Keefe and Burgess (2005) Hippocampus 15:853,866). The original one-dimensional interference model is generalized to an appropriate two-dimensional mechanism. Specifically, dendritic subunits of layer II medial entorhinal stellate cells provide multiple linear interference patterns along different directions, with their product determining the firing of the cell. Connection of appropriate speed- and direction- dependent inputs onto dendritic subunits could result from an unsupervised learning rule which maximizes postsynaptic firing (e.g. competitive learning). These inputs cause the intrinsic oscillation of subunit membrane potential to increase above theta frequency by an amount proportional to the animal's speed of running in the "preferred" direction. The phase difference between this oscillation and a somatic input at theta-frequency essentially integrates velocity so that the interference of the two oscillations reflects distance traveled in the preferred direction. The overall grid pattern is maintained in environmental location by phase reset of the grid cell by place cells receiving sensory input from the environment, and environmental boundaries in particular. We also outline possible variations on the basic model, including the generation of grid-like firing via the interaction of multiple cells rather than via multiple dendritic subunits. Predictions of the interference model are given for the frequency composition of EEG power spectra and temporal autocorrelograms of grid cell firing as functions of the speed and direction of running and the novelty of the environment. © 2007 Wiley-Liss, Inc. [source] Competitive interactions between endogenous LTD and LTP in the hippocampus underlie the storage of emotional memories and stress-induced amnesiaHIPPOCAMPUS, Issue 8 2005David M. Diamond Abstract This speculative review serves two purposes. First, it as an extension of the ideas we developed in a previous review (Diamond et al., Hippocampus, 2004;14:281,291), and second, it is a rebuttal to Abraham's (Hippocampus, 2004;14:675,676) critique of that review. We had speculated on the functional significance of the finding that post-training LTP induction produces retrograde amnesia. We noted the similarities between the findings that strong tetanizing stimulation can produce LTP and retrograde amnesia, and that a strong emotional experience can produce a long-lasting memory and retrograde amnesia, as well. The commonalities between LTP induction and emotional learning provided the basis of our hypothesis that an emotional experience generates endogenous LTD/depotentiation, which reverses synaptic plasticity formed during previous learning experiences, and endogenous LTP, which underlies the storage of new information. Abraham raised several concerns with our review, including the criticism that our speculation "falters because there is no evidence that stress causes LTD or depotentiation," and that research on stress and hippocampus has "failed to report any LTP-like changes." Abraham's points are well-taken because stress, in isolation, does not appear to generate long-lasting changes in baseline measures of hippocampal excitability. Here, within the context of a reply to Abraham's critique, we have provided a review of the literature on the influence of stress, novelty, fear conditioning, and the retrieval of emotional memories on cognitive and physiological measures of hippocampal functioning. An emphasis of this review is our hypothesis that endogenous forms of depotentiation, LTD and LTP are generated only when arousing experiences occur in conjunction with memory-related activation of the hippocampus and amygdala. We conclude with speculation that interactions among the different forms of endogenous plasticity underlie a form of competition by synapses and memories for access to retrieval resources. © 2005 Wiley-Liss, Inc. [source] A learning rule for place fields in a cortical model: Theta phase precession as a network effectHIPPOCAMPUS, Issue 7 2005Silvia Scarpetta Abstract We show that a model of the hippocampus introduced recently by Scarpetta et al. (2002, Neural Computation 14(10):2371,2396) explains the theta phase precession phenomena. In our model, the theta phase precession comes out as a consequence of the associative-memory-like network dynamics, i.e., the network's ability to imprint and recall oscillatory patterns, coded both by phases and amplitudes of oscillation. The learning rule used to imprint the oscillatory states is a natural generalization of that used for static patterns in the Hopfield model, and is based on the spike-time-dependent synaptic plasticity, experimentally observed. In agreement with experimental findings, the place cells' activity appears at consistently earlier phases of subsequent cycles of the ongoing theta rhythm during a pass through the place field, while the oscillation amplitude of the place cells' firing rate increases as the animal approaches the center of the place field and decreases as the animal leaves the center. The total phase precession of the place cell is lower than 360°, in agreement with experiments. As the animal enters a receptive field, the place cells' activity comes slightly less than 180° after the phase of maximal pyramidal cell population activity, in agreement with the findings of Skaggs et al. (1996, Hippocampus 6:149,172). Our model predicts that the theta phase is much better correlated with location than with time spent in the receptive field. Finally, in agreement with the recent experimental findings of Zugaro et al. (2005, Nature Neuroscience 9(1):67,71), our model predicts that theta phase precession persists after transient intrahippocampal perturbation. © 2005 Wiley-Liss, Inc. [source] Neuropeptide Y delays hippocampal kindling in the ratHIPPOCAMPUS, Issue 5 2003Sophie Reibel Abstract Chronic intrahippocampal infusion of the neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to delay kindling epileptogenesis in the rat and several lines of evidence suggest that neuropeptide Y could mediate these inhibitory effects. Chronic infusion of BDNF leads to a sustained overexpression of neuropeptide Y in the hippocampus, which follows a time course similar to that of the suppressive effects of BDNF on kindling. In vivo, acute applications of neuropeptide Y or agonists of its receptors exert anticonvulsant properties, especially on seizures of hippocampal origin. In this study, we examined how chronic infusion of this neuropeptide in the hippocampus affected kindling epileptogenesis. A 7-day continuous infusion of neuropeptide Y in the hippocampus delayed the progression of hippocampal kindling in the rat, whereas anti-neuropeptide Y immunoglobulins had an aggravating effect. These results show that neuropeptide Y exerts anti-epileptogenic properties on seizures originating within the hippocampus and lend support to the hypothesis that BDNF delays kindling at least in part through upregulation of this neuropeptide. They also suggest that the seizure-induced upregulation of neuropeptide Y constitutes an endogenous mechanism counteracting excessive hippocampal excitability. Hippocampus 2003;13:557,560. © 2003 Wiley-Liss, Inc. [source] Changes in NOS protein expression and activity in the rat hippocampus, entorhinal and postrhinal cortices after unilateral electrolytic perirhinal cortex lesionsHIPPOCAMPUS, Issue 5 2003Ping Liu Abstract The integrity of the perirhinal cortex is critical for certain types of learning and memory. One important issue relating to the function of this region is its interaction with other brain areas that play a role in memory processing. This study investigates the time course of changes in activity and protein expression of nitric oxide synthase (NOS), which transforms L -arginine into nitric oxide (NO) and citrulline, in the hippocampus and the entorhinal and postrhinal cortices after unilateral electrolytic lesions of the perirhinal cortex. Electrolytic lesions of the perirhinal cortex resulted in long lasting changes in NOS activity and protein expression in the entorhinal and postrhinal cortices (,2 weeks post-lesion). In contrast, there was a small and transient decrease in nNOS expression (with no change in NOS activity) in the dorsal portion of the hippocampus. iNOS was not expressed in any region examined at any time point. These findings provide the first evidence that electrolytic lesions of the perirhinal cortex can result in long-term neurochemical changes in its anatomically related structures. Given that NO has been implicated in neuroplasticity processes, the interpretation of memory impairments induced by electrolytic lesions of the perirhinal cortex (and possibly, therefore, other brain regions) need to be considered with regard to these findings. Hippocampus 2003;13:561,571. © 2003 Wiley-Liss, Inc. [source] Dissociable neural responses in the hippocampus to the retrieval of facial identity and emotion: An event-related fMRI studyHIPPOCAMPUS, Issue 4 2003Tetsuya Iidaka Abstract In studies with brain-damaged patients and experimental animals, the medial temporal lobe, including the hippocampus and parahippocampal gyrus, has been found to play a critical role in establishing declarative or episodic memory. We measured the neural response in these structures, using event-related functional magnetic resonance imaging, while six healthy subjects performed the retrieval task for facial identity and emotion, respectively. Under the identity condition, the subjects participated in a yes/no recognition test for neutral faces learned before the scanning. Under the emotion condition, the subjects learned the faces with positive or negative expression and retrieved their expressions from neutral cue faces. The results showed that the left hippocampus is primarily involved in the identification of learned faces, and that the adjacent parahippocampal gyrus responds more to target than to distracter events. These results indicate a specific engagement of the left hippocampal regions in conscious recollection and identification of physiognomic facial features. The activity in the right hippocampus increased under both the identity and emotion conditions. The present results may relate with the functional model of face recognition in which the left hemisphere contributes to the processing of detailed features and the right hemisphere is efficient in the processing of global features. Hippocampus 2003;13:429,436. © 2003 Wiley-Liss, Inc. [source] Reversible inactivation of the hippocampal formation in food-storing black-capped chickadees (Poecile atricapillus)HIPPOCAMPUS, Issue 4 2003Michael W. Shiflett Abstract The role of the hippocampal formation (HF) in memory processing was assessed in food-storing black-capped chickadees (Poecile atricapilla) by reversibly inactivating the HF during different memory tests. The memory tests required birds to remember a location based on spatial cues only, or based on a combination of both spatial and distinct visual cues. Inactivation of the HF impaired short-term spatial memory, but not visual-spatial memory. Inactivation of the HF impaired the retrieval of short-term (15 min) spatial memories, but not long-term (3-h) spatial memories. The pattern of deficits produced by inactivation of the HF in chickadees suggests a possible function of the hippocampal specialization of food-storing birds, as well as extends the notion of functional homology between the avian and mammalian HF. Hippocampus 2003;13:437,444. © 2003 Wiley-Liss, Inc. [source] Learning associations between places and visual cues without learning to navigate: Neither fornix nor entorhinal cortex is requiredHIPPOCAMPUS, Issue 4 2003E.A. Gaffan Abstract 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. Rats learned eight visual discriminations among computer-displayed scenes in a Y-maze, using the constant-negative paradigm. Every discrimination problem included two familiar scenes (constants) and many less familiar scenes (variables). On each trial, the rats chose between a constant and a variable scene, with the choice of the variable rewarded. In six problems, the two constant scenes had correlated spatial properties, either Allo (each constant appeared always in the same maze arm) or Ego (each constant always appeared in a fixed direction from the start arm) or both (Allo + Ego). In two No-Cue (NC) problems, the two constants appeared in randomly determined arms and directions. Intact rats learn problems with an added Allo or Ego cue faster than NC problems; this facilitation provides indirect evidence that they learn the associations between scenes and spatial cues, even though that is not required for problem solution. 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. Similar facilitation was seen in subgroups that had short or long prior experience with the apparatus and task. Therefore, neither major hippocampal input,output system is crucial for learning about allocentric or egocentric cues in this paradigm, which does not require rats to control their choices or navigation directly by spatial cues. Hippocampus 2003;13:445,460. © 2003 Wiley-Liss, Inc. [source] Function of hippocampus in "insight" of problem solvingHIPPOCAMPUS, Issue 3 2003Jing Luo Abstract Since the work of Wolfgang Köhler, the process of "insight" in problem solving has been the subject of considerable investigation. Yet, the neural correlates of "insight" remain unknown. Theoretically, "insight" means the reorientation of one's thinking, including breaking of the unwarranted "fixation" and forming of novel, task-related associations among the old nodes of concepts or cognitive skills. Processes closely related to these aspects have been implicated in the hippocampus. In this research, the neural correlates of "insight" were investigated using Japanese riddles, by imaging the answer presentation and comprehension events, just after participants failed to resolve them. The results of event-related functional magnetic resonance imaging (fMRI) analysis demonstrated that the right hippocampus was critically highlighted and that a wide cerebral cortex was also involved in this "insight" event. To the best of our knowledge, this work is the first neuroimaging study to have investigated the neural correlates of "insight" in problem solving. Hippocampus 2003;13:316,323. © 2003 Wiley-Liss, Inc. [source] Involuntary, unreinforced (pure) spatial learning is impaired by fimbria-fornix but not by dorsal hippocampus lesionsHIPPOCAMPUS, Issue 3 2003Norman M. White Abstract Pure spatial learning occurs when rats acquire information about an environment while exploring it in the absence of reinforcers. We previously reported that voluntary, unreinforced exploration of a radial maze retards subsequent reinforced conditioned cue preference (CCP) learning in the same maze. In the present experiment, we examined the effects of involuntary, unreinforced pre-exposure to a radial maze. During pre-exposure, rats were moved by an experimenter between the ends of two arms of a radial maze five times in 30 min. This form of pre-exposure retarded CCP learning, whereas rats that were not pre-exposed and rats that were pre-exposed to a maze in a different room displayed normal CCP learning. These findings suggest that some information specific to the maze environment was acquired during involuntary unreinforced pre-exposure to it. 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. Large neurotoxic lesions of the dorsal hippocampus made before pre-exposure had no effect on the retardation of CCP learning, but the rats with these lesions were impaired on a standard test of reinforced spatial learning in a water maze. The lesion effects in experiment 2 are similar to those previously reported for voluntary exploration and suggest that pure spatial learning may occur during both voluntary exploration of and involuntary exposure to an environment in the absence of reinforcers. Pure spatial learning can apparently occur with exposure to two different locations within an environment, but the rats do not have to move between the locations voluntarily. An intact fimbria-fornix is required for acquisition but not expression of this form of learning. The hippocampus is not involved in this form of learning. Hippocampus 2003;13:324,333. © 2003 Wiley-Liss, Inc. [source] Transitivity, flexibility, conjunctive representations, and the hippocampus.HIPPOCAMPUS, Issue 3 2003Abstract After training on a set of four ordered, simultaneous, odor discrimination problems (A+B,, B+C,, C+D,, D+E), intact rats display transitivity: When tested on the novel combination BD, they choose B. Rats with damage to the hippocampus, however, do not show transitivity (Dusek and Eichenbaum, 1997. Proc Natl Acad Sci U S A 94:7109,7114). These results have been interpreted as support for the idea that the hippocampus is a relational memory storage system that enables the subject to make comparisons among representations of the individual problems and choose based on inferential logic. We provide evidence for a simpler explanation. Specifically, subjects make their choices based on the absolute excitatory value of the individual stimuli. This value determines the ability of that stimulus to attract a response. This conclusion emerged because after training on a five-problem set (A+B,, B+C,, C+D,, D+E,, E+F,) rats preferred B when tested with BE, but not when tested with BD. The implication of these results for how to conceptualize the role of the hippocampus in transitive-like phenomena is discussed. Hippocampus 2003;13:334,340. © 2003 Wiley-Liss, Inc. [source] Representation of place by monkey hippocampal neurons in real and virtual translocationHIPPOCAMPUS, Issue 2 2003Etsuro Hori Abstract The hippocampal formation (HF) is hypothesized as a neuronal substrate of a cognitive map, which represents environmental spatial information by an ensemble of neural activity. However, the relationships between the hippocampal place cells and the cognitive map have not been clarified in monkeys. The present study was designed to investigate how activity patterns of place-selective neurons encode spatial relationships of various environmental stimuli; to do this, we used multidimensional scaling (MDS) for hippocampal neuronal activity in the monkey during the performance of real and virtual translocation. Of 389 neurons recorded from the monkey HF and parahippocampal gyrus (PH), 166 had place fields that displayed increased activity in a specific area of an experimental field and/or on a monitor (place-selective neurons). The MDS transformed relationships among the 16 places in the experimental field and the monitor, expressed as correlation coefficients between all possible pairs of two places based on the 166 place-selective responses, into geometric relationships in a two-dimensional MDS space. In the real translocation tasks, the 16 places were distributed throughout the MDS space, and their relative positions were well correlated to real positions in the experimental laboratory. However, the correlation between the MDS space and real arrangements was significantly smaller in virtual than real translocation tasks. The present results strongly suggest that activity patterns of the HF and PH neurons represent spatial information and might provide a neurophysiological basis for a cognitive map. Hippocampus 2003;13:190,196. © 2003 Wiley-Liss, Inc. [source] Hippocampal lesions and discrimination performance of mice in the radial maze: Sparing or impairment depending on the representational demands of the taskHIPPOCAMPUS, Issue 2 2003Nicole Etchamendy Abstract The effects of ibotenate hippocampal lesions on discrimination performance in an eight-arm radial maze were investigated in mice, using a three-stage paradigm in which the only parameter that varied among stages was the way the arms were presented. In the initial learning phase (stage 1), animals learned the valence or reward contingency associated with six (three positive and three negative) adjacent arms of the maze using a successive (go/no-go) discrimination procedure. In the first test phase (stage 2), the six arms were grouped into three pairs, so that on each trial, the subject was faced with a choice between two adjacent arms of opposite valence (concurrent two-choice discrimination). In the second test phase (stage 3), the subject was faced with all six arms simultaneously (six-choice discrimination). Hippocampal-lesioned mice acquired the initial learning phase at a near-normal rate but behaved as if they had learned nothing when challenged with the two-choice discriminations at stage 2. In contrast, they behaved normally when confronted with the six-choice discrimination at stage 3. Detailed examination of within- and between-stage performance suggests that hippocampal-lesioned mice perform as intact mice when presentation of the discriminanda encourages the storage and use of separate representations (i.e., in initial learning and six-choice discrimination testing), but that they fail in test situations that involve explicit comparisons between such separate representations (two-choice discriminations), hence requiring the use of relational representations. Hippocampus 2003;13:197,211. © 2003 Wiley-Liss, Inc. [source] Distribution and morphology of serotonin-immunoreactive axons in the hippocampal region of the New Zealand white rabbit.HIPPOCAMPUS, Issue 1 2003Abstract This study provides a detailed light microscopic description of the morphology and distribution of immunohistochemically stained serotonergic axons in the hippocampal region of the New Zealand white rabbit. The serotonergic axons were segregated morphologically into three types: beaded fibers, fine fibers, and stem-axons, respectively. Beaded fibers were thin serotonergic axons with large varicosities, whereas thin axons with small fusiform or granular varicosities were called fine fibers. Finally, thick straight non-varicose axons were called stem-axons. Beaded fibers often formed large conglomerates with numerous boutons (pericellular arrays) in close apposition to the cell-rich layers in the hippocampal region, e.g., the granular and hilar cell layers of the dentate area and the pyramidal cell layer ventrally in CA3. The pericellular arrays in these layers were often encountered in relation to small calbindin-D28K -positive cells, as shown by immunohistochemical double staining for serotonin and calbindin-D28K. The beaded and fine serotonergic fibers displayed a specific innervation pattern in the hippocampal region and were encountered predominantly within the terminal field of the perforant path, e.g., the stratum moleculare hippocampi and the outer two-thirds of the dentate molecular layer. These fibers were also frequently seen in the deep part of the stratum oriens and the alveus, forming a dense plexus in relation to large multipolar calbindin-D28K -positive cells and their basal extensions. Stem-axons were primarily seen in the fimbria and alveus. This innervation pattern was present throughout the entire hippocampal formation, but there were considerable septotemporal differences in the density of the serotonergic innervation. A high density of innervation prevailed in the ventral/temporal part of the hippocampal formation, whereas the dorsal/septal part received only a moderate to weak serotonergic innervation. These results suggest that the serotonergic system could modulate the internal hippocampal circuitry by way of its innervation in the terminal field of the perforant path, the hilus fasciae dentatae, and ventrally in the zone closely apposed to the mossy fiber layer and the pyramidal cells of CA3. This modulation could be of a dual nature, mediated directly by single serotonergic fibers traversing the hippocampal layers or indirectly by the pericellular arrays and their close relation to the calbindin-D28K -positive cells. The marked septotemporal differences in innervation density point toward a difference between the ventral and dorsal parts of the hippocampal formation with respect to serotonergic function and need for serotonergic modulation. Hippocampus 2003;13:21,37. © 2003 Wiley-Liss, Inc. [source] Effect of halothane on type 2 immobility-related hippocampal theta field activity and theta-on/theta-off cell dischargesHIPPOCAMPUS, Issue 1 2003Brian H. Bland Abstract Rats were studied in acute and chronic (freely moving) recording conditions during exposure to different levels of the volatile anesthetic halothane, in order to assess effects on hippocampal theta field activity in the chronic condition and on theta-related cellular discharges in the acute condition. Previous work has shown that the generation of hippocampal type 2 theta depends on the coactivation of cholinergic and GABAergic inputs from the medial septum. Based on these data and recent findings that halothane acts on interneuron GABAA receptors, we predicted that exposure of rats to subanesthetic levels would result in the induction of type 2 theta field activity. In the chronic condition, exposure to subanesthetic levels of halothane (0.5,1.0 vol %) was found to induce theta field activity during periods of immobility (type 2 theta) with a mean increase of 39% in amplitude (mV) compared to control levels during movement. The total percentage of signal power (V2) associated with peak theta frequencies (80% compared to control levels of 47%) was also increased by halothane. Over the whole range of administered halothane concentrations, theta field frequency progressively declined from a mean peak frequency of 6.5 ± 0.8 Hz at 0.5 vol % halothane to a mean peak frequency of 4.0 ± 1.8 Hz at 2.0 vol % halothane. Subsequent administration of a muscarinic cholinergic antagonist, atropine sulfate, selectively abolished all type 2 immobility-related theta field activity, while type 1 movement-related theta was still intact. At anesthetic levels (1.5,2.0 vol %) in acute experiments, hippocampal field activity spontaneously cycled between theta and large-amplitude irregular activity. Analysis of depth profiles in four experiments revealed they were identical to those previously described for rats under urethane anesthesia conditions. In addition, the discharge properties of 31 theta-related cells, classified as tonic and phasic theta-on and tonic and phasic theta-off cells, did not differ significantly from those described previously in rats anesthetized with urethane. These data provide further support for an involvement of GABAA receptors in the generation of hippocampal theta. Hippocampus 2003;13:38,47. © 2003 Wiley-Liss, Inc. [source] Differential contributions of the parahippocampal place area and the anterior hippocampus to human memory for scenesHIPPOCAMPUS, Issue 6 2002Stefan Köhler Abstract Past neuroimaging research has identified a parahippocampal place area (PPA) in the posterior medial temporal lobe (MTL), which responds preferentially to visual scenes and plays a role in episodic memory for this class of stimuli. In the present positron emission tomography study, we examined to what extent the functional characteristics of the PPA resemble those of other, more anterior MTL regions across various learning and recognition-memory tasks. We also determined whether the involvement of the PPA in recognition of previously studied scenes is specific to a particular type of scene information. We found that, like the PPA, anterior hippocampal regions showed a novelty response (higher activation for novel than repeated scenes) and a stimulus-related response (higher activation for scenes than objects) during learning, indicating that MTL structures other than the PPA contribute to the encoding of novel stimulus relationships in scenes. However, these anterior hippocampal regions showed no involvement during recognition of either spatial or nonspatial information contained in scenes. The PPA, by contrast, was consistently involved in recognition of all types of scene details, presumably through interactions with co-activated parietal and occipitotemporal cortices. We suggest that MTL contributions from the PPA are sufficient to support recognition of scenes when the task can be based on a perceptually based familiarity process. Hippocampus 2002;12:718,723. © 2002 Wiley-Liss, Inc. [source] Single neuron burst firing in the human hippocampus during sleepHIPPOCAMPUS, Issue 6 2002Richard J. Staba Abstract Although there are numerous non-primate studies of the single neuron correlates of sleep-related hippocampal EEG patterns, very limited hippocampal neuronal data are available for correlation with human sleep. We recorded human hippocampal single neuron activity in subjects implanted with depth electrodes required for medical diagnosis and quantitatively evaluated discharge activity from each neuron during episodes of wakefulness (Aw), combined stage 3 and 4 slow-wave sleep (SWS), and rapid eye movement (REM) sleep. The mean firing rate of the population of single neurons was significantly higher during SWS and Aw compared with REM sleep (p = 0.002; p < 0.0001). In addition, burst firing was significantly greater during SWS compared with Aw (p = 0.001) and REM sleep (p < 0.0001). The synchronized state of SWS and associated high-frequency burst discharge found in human hippocampus may subserve functions similar to those reported in non-primate hippocampus that require burst firing to induce synaptic modifications in hippocampal circuitry and in hippocampal projections to neocortical targets that participate in memory consolidation. Hippocampus 2002;12:724,734. © 2002 Wiley-Liss, Inc. [source] Regulated transcription of the immediate-early gene Zif268: Mechanisms and gene dosage-dependent function in synaptic plasticity and memory formationHIPPOCAMPUS, Issue 5 2002Bruno Bozon Abstract The immediate-early gene Zif268 is a member of the Egr family of inducible transcription factors. Data from gene expression studies have suggested that this gene may play a critical role in initial triggering of the genetic machinery that has long been considered a necessary mechanism for maintenance of the later phases of LTP and also for the consolidation or stabilization of long-lasting memories. Until recently, however, the data supporting this assumption have been based primarily on circumstantial evidence, with no direct evidence to suggest that Zif268 is required for long-lasting synaptic plasticity and memory. In this report, we review our own data using Zif268 mutant mice; we show that although the early phase of dentate gyrus LTP is normal in these mice, the later phases are not present, and the ability of the mice to maintain learned information over a 24-h period is deficient. In addition, we present new information showing a task-dependent gene dosage effect in Zif268 heterozygous mice. We show that spatial learning is particularly sensitive to reduced levels of Zif268, as one-half of the complement of Zif268 in heterozygous mice is insufficient to maintain spatial long-term memories. Hippocampus 2002;12:570,577. © 2002 Wiley-Liss, Inc. [source] Neurogenesis may relate to some but not all types of hippocampal-dependent learningHIPPOCAMPUS, Issue 5 2002Tracey J. Shors Abstract The hippocampal formation generates new neurons throughout adulthood. Recent studies indicate that these cells possess the morphology and physiological properties of more established neurons. However, the function of adult generated neurons is still a matter of debate. We previously demonstrated that certain forms of associative learning can enhance the survival of new neurons and a reduction in neurogenesis coincides with impaired learning of the hippocampal-dependent task of trace eyeblink conditioning. Using the toxin methylazoxymethanol acetate (MAM) for proliferating cells, we tested whether reduction of neurogenesis affected learning and performance associated with different hippocampal dependent tasks: spatial navigation learning in a Morris water maze, fear responses to context and an explicit cue after training with a trace fear paradigm. We also examined exploratory behavior in an elevated plus maze. Rats were injected with MAM (7 mg/kg) or saline for 14 days, concurrent with BrdU, to label new neurons on days 10, 12, and 14. After treatment, groups of rats were tested in the various tasks. A significant reduction in new neurons in the adult hippocampus was associated with impaired performance in some tasks, but not with others. Specifically, treatment with the antimitotic agent reduced the amount of fear acquired after exposure to a trace fear conditioning paradigm but did not affect contextual fear conditioning or spatial navigation learning in the Morris water maze. Nor did MAM treatment affect exploration in the elevated plus maze. These results combined with previous ones suggest that neurogenesis may be associated with the formation of some but not all types of hippocampal-dependent memories. Hippocampus 2002;12:578,584. © 2002 Wiley-Liss, Inc. [source] Contribution of T-type VDCC to TEA-induced long-term synaptic modification in hippocampal CA1 and dentate gyrusHIPPOCAMPUS, Issue 5 2002Dong Song Abstract We have previously reported that exposure to the K+ channel blocker tetraethylammonium (TEA), 25 mM, induces long-term potentiation (LTP) in CA1, but not in the dentate gyrus (DG), of the rat hippocampal slice. During TEA application, stimulation of excitatory afferents results in a strong depolarizing potential after the fast excitatory postsynaptic potential (EPSP) in CA1, but not in DG. We hypothesized that the differential effect of TEA on long-term synaptic modification in CA1 and DG results from different levels of TEA-elicited depolarization in the two cell types. Additional pharmacological studies showed that blockade of T-type voltage-dependent calcium channels (VDCCs) decreased both the magnitude of LTP and the late, depolarizing potential in CA1. Blockade of L-type VDCCs had no such effect. Using computer models of morphologically reconstructed CA1 pyramidal cells and DG granule cells, we tested our hypothesis by simulating the relative intracellular Ca2+ accumulation and membrane potential changes mediated by T-type and L-type VDCCs. Simulation results using pyramidal cell models showed that, with decreased maximum conductance of TEA-sensitive potassium channels, synaptic inputs elicited strong depolarizing potentials similar to those observed with intracellular recording. During this depolarization, VDCCs were opened and resulted in a large intracellular Ca2+ accumulation that presumably caused LTP. When T-type VDCCs were blocked, the magnitudes of both the Ca2+ accumulation and the late depolarizing potential were decreased substantially. Simulated blockade of L-type VDCCs had only a minor effect. Together, our modeling and experimental studies indicate that T-type VDCCs, rather than L-type VDCCs, are primarily responsible for facilitating the depolarizing potential caused by TEA and for the consequent Ca2+ influx. Thus, our findings strongly suggest that the induction of TEA-LTP in CA1 depends primarily on T-type, rather than L-type, VDCCs. Simulation results using modeled granule cells suggests that the failure of TEA to induce LTP in DG is partly due to a low density of T-type VDCCs in granule cell membranes. Hippocampus 2002;12:689,697. © 2002 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||