bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasopressin induction of long‐lasting potentiation of synaptic transmission in the dentate gyrus
Authors: Chen Chong , Brinton Roberta Díaz , Shors Tracey J. , Thompson Richard F.
Published: May 2005

Vasopressin receptors are present in both the developing and mature dentate gyrus of the rat brain and are of the V1 vasopressor type. Because vasopressin has been shown to influence memory function when injected into the dentate gyrus, the influence of this peptide on an electrophysiological model of learning and memory using the field excitatory postsynaptic potential (EPSP) of the dentate gyrus was investigated. Results of these studies showed that nanomolar concentrations of [Arg8]‐vasopressin induced a prolonged increase in the amplitude and slope of the evoked population response in the presence of 1.5 mM calcium. Moreover, the expression of the vasopressin‐induced potentiation of the EPSP persisted following removal of vasopressin from the perfusion medium. The vasopressin‐induced sustained increase has been termed long‐term vasopressin potentiation (LTVP). The closely related neuropeptide oxytocin had no effect upon the EPSP of the dentate gyrus. Preincubation of hippocampal slices in a selective V1 antagonist blocked the expression of LTVP. The ability of the V1 antagonist to block LTVP demonstrates that the potentiation induced by vasopressin is receptor‐specific. In the presence of 2.5 mM calcium, the effect of vasopressin was opposite to that observed in 1.5 mM calcium. Under the conditions of 2.5 calcium, vasopressin induced a prolonged depression in the amplitude and slope of the EPSP. Expression of both potentiation and depression appeared within 5 minutes of application and persisted for the length of the observation, 60 minutes. These experiments demonstrate that vasopressin can induce long‐lasting changes in the excitability of dentate gyrus neurons that are both calcium‐dependent and receptor‐specific.
Alterations in [3H]‐kainate receptor binding in the hippocampal formation of aged long‐evans rats
Authors: Nagahara Alan H. , Nicolle Michelle M. , Gallagher Michela
Published: May 2005

The present study used in vitro autoradiography to examine the density of [3H]‐kainate (KA) binding in subregions of the hippocampal formation and certain cortical areas in young (7–8 months) and aged (27–29 months) Long‐Evans rats. In addition, the topography of KA binding in the dentate molecular layer was examined for evidence of reactive reorganization in the aged brain. This investigation of age‐related changes in [3H]‐KA binding included correlations with the animals' spatial learning performance in a Morris water maze. The results showed an age‐related decrease in the density of [3H]‐KA binding in several regions of the hippocampal formation (CA3, CA1, hilus) and within related cortical areas (subicular complex, entorhinal cortex, perirhinal cortex). In addition, an expanded zone of KA binding in the molecular layer of the dentate gyrus was observed in the aged group. This expansion of KA binding may reflect sprouting due to a loss of perforant path input to the dentate. The results of additional correlational analyses, however, indicated that these changes in the density and topography of [3H]‐KA binding were not strongly correlated with a decline in place learning ability.
Phase relationship between hippocampal place units and the EEG theta rhythm
Authors: O'Keefe John , Recce Michael L.
Published: May 2005

Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroer cephalograph theta pattern of rhythmical waves (7–12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100° to 355° in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified.
Hyperpolarizing synaptic potentials evoked in CA1 pyramidal cells by glutamate stimulation of interneurons from the oriens/alveus border of rat hippocampal slices. I. Electrophysiological response properties
Authors: Samulack Donald D. , Williams Sylvain , Lacaille Jean‐Claude
Published: May 2005

To examine the inhibitory postsynaptic potentials (IPSPs) elicited in pyramidal cells by interneurons situated at the stratum oriens/alveus border (O/A), glutamate was applied by micropressure to this area during intracellular recordings from CA1 pyramidal cells. Glutamate stimulation evoked IPSPs (glut‐IPSPs) of small amplitude (4 mV), delayed peak latency (100–110 ms), and long duration (300–400 ms). Recurrent activation of interneurons via glutamate stimulation of pyramidal cells by local application in stratum pyramidale (PYR) evoked recurrent IPSPs (PYR glut‐IPSPs) with similar amplitude and time course as O/A glut‐IPSPs. The mean equilibrium potential of O/A glut‐IPSPs (−77 mV) was significantly different from that of the PYR glut‐IPSPs (−71 mV), however, neither equilibrium potential was significantly different from that of the electrically evoked early IPSP in the same cells. Glutamate‐evoked IPSPs elicited from O/A displayed some response reversal (27% reversal) like those evoked from PYR (41% reversal). The early IPSP evoked by electrical stimulation displayed significantly more response reversal (67% reversal) than glut‐IPSPs. Both types of glut‐IPSPs (O/A and PYR) were associated with moderate increases in membrane conductance (5.9 and 6.6 nS, respectively), which were significantly less than the conductance change associated with the early IPSP (45.8 nS). In interneurons within PYR, glutamate stimulation in PYR readily elicited a flurry of excitatory postsynaptic potentials, whereas glutamate stimulation in O/A elicited IPSPs. The electrophysiological properties of IPSPs elicited in pyramidal cells by glutamate stimulation of interneurons in O/A were similar to those of recurrent IPSPs evoked from PYR. Given that both of these types of glutamate‐evoked IPSPs were mostly mediated via GABAA receptor channels (Samulack DD, Lacaille J‐C, 1993, Hippocampus 3:345–358), the small differences observed between equilibrium potentials, response reversals, and conductance changes could be due to a more electrotonically distant location from the soma of the synapses involved in O/A glut‐IPSPs as compared to those of recurrent IPSPs elicited from PYR.
Learning and memory after adrenalectomy‐induced hippocampal dentate granule cell degeneration in the rat
Authors: Armstrong John N. , McIntyre Dan C. , Neubort Simon , Sloviter Robert S.
Published: May 2005

Adrenalectomy (ADX) of normal adult rats causes selective hippocampal dentate granule cell degeneration that is prevented by corticosterone. The ability to destroy this one hippocampal cell type noninvasively made it possible to address the role of the dentate granule cells in learning and memory. Four months after ADX, 31 of 45 rats failed to show obvious granule cell loss and displayed behavior in the Morris water maze that was similar to 16 sham‐operated control rats and 16 ADX rats maintained on corticosterone throughout the study. Conversely, 14 of the 45 ADX rats experienced a loss of granule cells that varied from minimal to extensive. Although there were no obvious differences between groups in motoric and motivational characteristics or search strategies, ADX rats with moderate to extensive granule cell loss acquired place learning slightly slower than controls or ADX rats with minimal or no obvious cell loss. Furthermore, the ADX rats with moderate to extensive cell loss were temporarily impaired following alteration of either intramaze or extramaze cues compared to controls. In contrast, the rats with granule cell loss remembered an old place and learned a new place as quickly as controls. These results suggest that a normal complement of dentate granule cells may not be necessary for the acquisition or retention of spatial information in the Morris water maze.
Activation, travel distance, and environmental change influence food carrying in rats with hippocampal, medial thalamic and septal lesions: Implications for studies on hoarding and theories of hippocampal function
Authors: Whishaw Ian Q.
Published: May 2005

Rats transport food from exposed areas to covered areas where they eat it or leave it. Although there is evidence that limbic structures play a role in food transport, their role is controversial. Here it was found that although many rats with large hippocampal, septal/diagonal band of Broca or dorsomedial thalamic lesions did not carry food but ate it where they found it, a few presentations of an auditory stimulus could restore food carrying. Once restored, most features of food carrying in hippocampal rats were normal in relation to food presentation schedules, deprivation levels, ambient illumination, circadian cycles, food size, and eating times. Nevertheless, food carrying impairments reemerged when the testing environment was changed. Hippocampal rats were also excessively responsive to increases in travel distance and stopped carrying food at distances over which control rats would still carry large food pellets. Auditory stimulation did not restore food carrying over long travel distances. The findings that sensory stimulation, environmental change, and travel distance influence food carrying probabilities in rats with limbic system lesions is discussed in relation to research on limbic control of food hoarding and theories of limbic system function.
Perforated axospinous synapses with multiple, completely partitioned transmission zones: Probable structural intermediates in synaptic plasticity
Authors: Geinisman Yuri
Published: May 2005

Analysis of axospinous synapses in the rat dentate gyrus, using three‐dimensional reconstructions from electron micrographs of serial sections, revealed a novel synaptic subtype. Synapses of this subtype exhibit partitions that emanate from the postsynaptic spine head and invaginate the presynaptic axon terminal, dividing its portion contacted by the spine into distinct protrusions. Such complete spine partitions provide barriers between two to four discrete transmission zones, each one being formed by a separate axon terminal protrusion and delineated by a separate segment of the postsynaptic density (PSD). Spine partitions that differ from the complete ones were found in two other synaptic subtypes. One of these is characterized by a sectional partition the base of which is placed between the arms of a horseshoeshaped PSD. Synapses of another subtype exhibit a focal partition the base of which is restricted to a perforation in a fenestrated PSD. Although both sectional and focal partitions invaginate a presynaptic axon terminal, they do not divide into separate protrusions and do not split a single transmission zone into disjointed entities. All three subtypes of partitioned synapses have nonpartitioned counterparts exhibiting segmented, horseshoe‐shaped, or fenestrated PSDs. These observations suggest a model of structural modifications underlying synaptic plasticity. According to this model, synapses with multiple, completely partitioned transmission zones that appear to be designed as elements of an unusually high strength, represent pivotal structural intermediates in synaptic plasticity. The formation of such synapses from those that belong to other subtypes is postulated to result in a sustained increase in the efficacy of synaptic transmission. Conversely, a disassembly of complete partitions with the transformation of multiple transmission zones into a single one is proposed to lead to a persistent depression of synaptic respones.
Parvalbumin‐immunoreactive structures of the adult human entorhinal and transentorhinal region
Authors: Schmidt S. , Braak E. , Braak H.
Published: May 2005

Parvalbumin‐immunoreactive structures in the entorhinal and transentorhinal region of the adult human brain were studied using the avidin‐biotin‐peroxidase technique. Parvalbumin‐immunoreactive neurons and fibers (axons) were present in all layers (layer nomenclature according to Rose, 1927). The density of fibers was high in the islands of the superficial cell layer pre‐α and in layer pre‐β and still heavier in pre‐γ. In the subjacent lamina dissecans it diminished abruptly and remained low in all layers of the internal principal stratum (layers pri‐α, ‐β, ‐γ). This low density of fibers facilitated recognition of axon cartridges in layers pri‐α and pri‐γ. Axon cartridges were also present within layers pre‐β and pre‐γ but were obscured by the dense fiber network there. Parvalbumin immunoreactivity was observed in the nerve cell soma and throughout the dendritic tree allowing the distinction of numerous nerve cell types. All parvalbumin‐immunoreactive neurons belonged to the class of nonpyramidal neurons. Their lipofuscin pigment patterns differed distinctly from that of the pyramidal and modified pyramidal neurons. Based on their location, soma size, and dendritic arborization, they were grouped as large, mediumsized, and small neurons either of the multipolar or bipolar (vertical or horizontal) type. One type could be identified as an axo‐axonic neuron, more specifically as a chandelier neuron generating axon cartridges. The dense fiber net within layer pre‐γ suggested the existence of another neuronal type, probably a neuron with an extended axonal ramification. The identified neurons were compared to neuronal types described in the literature from Golgi studies.
Transneuronal changes in dendrites of GABAergic parvalbumin‐containing neurons of the rat fascia dentata following entorhinal lesion
Authors: Nitsch Robert , Frotscher Michael
Published: May 2005

The perforant path fibers from the entorhinal cortex form synapses with both granule cells and GABAergic, parvalbumin‐containing (PARV) nongranule cells. The authors recently reported a persistent reduction of PARV‐positive dendrites in the termination zones of entorhinal fibers in the hippocampus proper and fascia dentata after lesion of the entorhinal cortex. In the present study the authors analyzed the effects of de‐entorhination on the ultrastructure of postsynaptic PARV‐positive dendrites in the molecular layer of the fascia dentata. PARV immunocytochemistry was performed 2, 8, 55, and 360 days after an ipsilateral entorhinal lesion and, for comparison, 10 days after an ipsilateral fimbria‐fornix transection that disconnects the hippocampus from its septal and commissural afferents. Two days after entorhinal lesion, the authors observed swelling of the tissue close to the hippocampal fissure. Adjacent distal dendritic tips of PARV‐positive dendrites in the former perforant path termination zone persisted 55 days after entorhinal lesion and could still be observed after postlesional survival times for 1 year. Degenerating axon terminals were still present 55 days following lesion and PARV‐positive dendrites exhibited abnormal invaginations. Fimbria transection did not result in similar dendritic changes in PARV‐positive neurons. The results indicate a long‐lasting process of reorganization in the molecular layer of the fascia dentata followin entorhinal lesion and persisting changes in the morphology of PARV‐immunoreactive dendrites. Entorhinal fibers seem to play a specific role for the maintenance of these dendrites, since similar changes did not occur following removal of septal and commissural fibers.
Mapping the differential effects of procaine on frequency and amplitude of reticularly elicited hippocampal rhythmical slow activity
Authors: Kirk I. J. , McNaughton N.
Published: May 2005

Hippocampal rhythmical slow activity (RSA, theta) was elicited in urethanized rats by high‐frequency stimulation in the reticular formtion. The effects of procaine infusion (0.5 μL, 20% wt/vol) at various loci in the ascending system from pontine reticular formation to the medial septum/diagonal band area were investigated. It was found that procaine injected at points in the ascending system anterior to the supramamillary nucleus, in the region of the medial forebrain bundle or in the medial septum, reduced the amplitude of reticularly elicited RSA but had no effect on its frequency. Procaine injected at points in the ascending system from just anterior to the reticular formation stimulation site, up to, and including the supramamillary nucleus, reduced both the frequency and amplitude of reticularly elicited RSA. These results indicate that the frequency of reticularly elicited RSA is encoded in the supramamillary area, rather than in the medial septum/diagonal band as have previously been suggested.
Rapid decline of GABAA receptor subunit mrna expression in hippocampus following transient cerebral ischemia in the gerbil
Authors: Li Huiling , Siegel Ruth E. , Schwartz Rochelle D.
Published: May 2005

Inhibitory neurotransmission may play an important role in neuronal degeneration following transient cerebral ischemia. We studied the effect of transient forebrain ischemia on the GABAA receptor system in the gerbil hippocampus. Gerbils were subjected to 5 minutes of bilateral carotid occlusion and were sacrificed at various times over 4 days following reperfusion. There was a substantial loss of pyramidal cells in the CA1 area of the hippocampus, granule cell layer of the dentate gyrus, and ventroposterior medial and ventroposterior lateral nuclei of the thalamus at any time following ischemia. Examination of brain slices by in situ hybridization histochemistry revealed that a change in expression of the GABAA receptor α1 and β2 subunit mRNAs occurred in two phases following onset of reperfusion. The early phase (rapid) occurred within the first 4 hours following reperfusion. The expression of mRNAs significantly decreased (up to 25%) within 1 hour after occlusion in CA1 and CA3 pyramidal cell layers of the hippocampus and in the granule cell layer of the dentate gyrus. The expression of the mRNAs in these regions continued to decrease for 4 hours (up to 43%). In the second phase, which began between 4 and 12 hours following reperfusion, mRNA expression started to return to control levels in CA3 hippocampus and in the dentate. However, expression of both mRNAs continued to decline slowly in the CA1 pyramidal cell layer (up to 85%) over the next 3 days, concomitantly with degeneration of the CA1 pyramidal cells. Expression of mRNAs in the ventroposterior medial or ventroposterior lateral nuclei of the thalamus was similar to control values. To determine if a change in GABAA receptor distribution paralleled changes in receptor subunit mRNA expression, we also measured the binding of [35S]t‐butylbicylophosphorothionate to GABAA receptor chloride channels. The t‐butylibicyclophosphorothionate [35S] binding decreased between 1 and 4 days after reperfusion in the dendritic fields of CA1 pyramidal cells (strata oriens, radiatum, and lacunosum‐moleculare) but not in the pyramidal cell body layer. These results indicate that expression of GABAA receptor subunit mRNAs decrease well before CA1 pyramidal cell degeneration and loss of GABAA receptors. At present, it is not clear if an early loss of mRNA expression after an ischemic insult leads to a functional defect in GABAA receptors. If so, a loss of GABA neurotransmission may contribute to the development of neuronal degeneration following cerebral ischemia. The maintenance of normal GABA neurotransmission in surviving cells may explain their resistance to ischemia‐induced neuronal death.
Electrophysiological characterization of CA2 pyramidal cells from epileptic humans
Authors: Williamson Anne , Spencer Dennis D.
Published: May 2005

The CA2 region of the hippocampus is more resistant to the principal cell loss seen in CA1 and CA3 in both animal models of temporal lobe epilepsy and in medial temporal lobe sclerosis (MTS), a common neuropathological finding in human temporal lobe epilepsy. There is extensive synaptic reorganization in the MTS hippocampi that is not seen in the hippocampi of patients with tumor–associated temporal lobe epilepsy (TTLE). The authors examined the electrophysiological properties of CA2 pyramidal cells from these two types of human hippocampi. The two main findings are that most MTS cells do not have clear evidence for inhibition yet do not fire synaptically evoked bursts; and that mossy fiber stimulation could evoke excitatory postsynaptic potentials (EPSPs) in the MTS tissue, but not the TTLE cells. These data suggest that in MTS, CA2 cells are resistant to firing epileptiform bursts which may account for their survival. Moreover, the granule cell–CA2 cell connection represents a novel from of synaptic plasticity in this disease. © 1994 Wiley‐Liss, Inc.
Astrocytic dye coupling in rat hippocampus: Topography, developmental onset, and modulation by protein kinase C
Authors: Konietzko Uwe , Müller Christian M.
Published: May 2005

Previous studies have shown that astrocytes constitute a functional syncytium whereas the cytoplasmata of individual cells are connected via gap junctions. Many studies have used cultured astrocytes and have examined electrical coupling with the help of double electrode techniques. Another approach has been the immunohistochemical detection of gap junction proteins in sections of brain tissue. From the results of these experiments it is difficult to infer the extent of astrocyticcoupling in situ. To get an impression of the distribution of coupled astrocytes we took advantage of the hippocampal slice preparation which leaves the topography of neurons and astrocytes intact. We performed injections of low molecular weight dyes into single electrophysiologically identified astrocyes. As these dyes can pass through gap junctions this leads to the staining of all connected cells in a certain area, limited by the diffusional spread of the dye. The results show that there is virtually no border to astrocytic coupling between the diverse hippocampal subdivisions. This widespread coupling could already be detected at postnatal day 4, the earliest age tested. Activation of protein kinase C with phorbol esters showed that it is possible to reduce gap junctional communication by some extent. We conclude that although no compartmentalization was seen with respect to astrocytic coupling, the intercellular communication of these glial cells has the capability of being regulated for example by neuronal signals which activate the phospholipase C pathway in astrocytes. © 1994 Wiley‐Liss, Inc.
Effects of medial septal or unilateral hippocampal inactivations on reference and working spatial memory in rats
Authors: Poucet B. , Buhot M.‐C.
Published: May 2005

The memory performances of rats receiving a reversible inactivation of either the medial septum or one side of the ventral hippocampus were compared in a radial arm maze task allowing the assessment of both working and reference memory. After pre‐surgery training, rats were chronically equipped with bilateral cannulae into the ventral hippocampus and a single cannula into the medial septum. Following post‐surgery retraining, animals received a series of test trials during which they received saline or lidocaine injections in either the medial septum or one side of the ventral hippocampus. Lidocaine injections in either structure resulted in both reference and working memory deficits. However, animals were more impaired after septal injections than after unilateral hippocampal injections. This result suggests that the septo‐hippocampal formation acts as a functionally homogeneous structure essential for spatial processing. © 1994 Wiley‐Liss, Inc.
Synaptic and intrinsic properties of neurons of origin of the perforant path in layer II of the rat entorhinal cortex in vitro
Authors: Jones Roland S. G.
Published: May 2005

Layer II of the entorhinal cortex (EC) provides the first step in the hippocampal trisynaptic loop via the perforant path projection to the dentate gyrus. While a great deal is known about this projection and the properties of the dentate granule cells, much less information is available concerning the properties of and synaptic inputs to the cells of origin of the pathway in layer II. The present experiments have employed a slice preparation of the rat EC to study the intrinsic membrane properties and synaptic organization of layer II neurons. Two types of neurons could be identified electrophysiologically. The majority were designated type I and displayed a pronounced time‐dependent inward rectification in the hyperpolarizing direction. Type II displayed little evidence of this characteristic. However, morphological examination suggested that both types were spiny stellate neurons projecting via the perforant path. Synaptic responses of both types displayed evidence of excitatory inputs mediated by both N‐methyl‐D‐aspartate (NMDA) and non‐NMDA glutamate receptors. In general, however, at low frequencies the responses were dominated by inhibitory inputs mediated by both GABAA and GABAB receptors. At higher frequencies the bias was shifted much more toward excitation. The contribution of synaptic and intrinsic properties of layer II neurons to the processing capabilities of the EC is discussed. © 1994 Wiley‐Liss, Inc.
Computational analysis of the role of the hippocampus in memory
Authors: Treves Alessandro , Rolls Edmund T.
Published: May 2005

The authors draw together the results of a series of detailed computational studies and show how they are contributing to the development of a theory of hippocampal function. A new part of the theory introduced here is a quantitative analysis of how backprojections from the hippocampus to the neocortex could lead to the recall of recent memories. The theory is then compared with other theories of hippocampal function. First, what is computed by the hippocampus is considered. The hypothesis the authors advocate, on the basis of the effects of damage to the hippocampus and neuronal activity recorded in it, is that it is involved in the formation of new memories by acting as an intermediate‐term buffer store for information about episodes, particularly for spatial, but probably also for some nonspatial, information. The authors analyze how the hippocampus could perform this function, by producing a computational theory of how it operates, based on neuroanatomical and neurophysiological information about the different neuronal systems contained within the hippocampus. Key hypotheses are that the CA3 pyramidal cells operate as a single autoassociation network to store new episodic information as it arrives via a number of specialized preprocessing stages from many association areas of the cerebral cortex, and that the dentate granule cell/mossy fiber system is important, particularly during learning, to help to produce a new pattern of firing in the CA3 cells for each episode. The computational analysis shows how many memories could be stored in the hippocampus and how quickly the CA3 autoassociation system would operate during recall. The analysis is then extended to show how the CA3 system could be used to recall a whole episodic memory when only a fragment of it is presented. It is shown how this recall could operate using modified synapses in backprojection pathways from the hippocampus to the cerebral neocortex, resulting in reinstatement of neuronal activity in association areas of the cerebral neocortex similar to that present during the original episode. The recalled information in the cerebral neocortex could then be used by the neocortex in the formation of long‐term memories. © 1994 Wiley‐Liss, Inc.
Non‐lamellar propagation of entorhinal influences in the hippocampal formation: Multiple electrode recordings in the isolated guinea pig brain in vitro
Authors: Paré Denis , Llinás Rodolfo
Published: May 2005

Experiments were carried out to study the spatiotemporal organization of medial entorhinal inputs to the hippocampal system. They were performed in the isolated guinea pig brain in vitro preparation as it provides easy access to the medial entorhinal cortex (mEC) which is difficult to reach in vivo. Multiple simultaneous field potential recordings along the septotemporal extent of the dentate granular layer revealed that the mEC projection to the dentate gyrus (DG) is organized topographically. Thus, stimulation of the caudal regions of the mEC elicited population spikes (PSs) in the septal pole of the DG while successively more rostral stimulation sites activated progressively more temporal sectors of the DG. However, threshold mEC stimuli never elicited PSs over more than one‐third of the DG.

In the CAl pyramidal layer, only trisynaptic PSs were evoked by the mEC stimulation (latency >20 ms at 30°C). However, PSs were widely distributed in the transverse and longitudinal axes of the hippocampus and, irrespective of the mEC stimulation site, the latency of CAl PSs gradually increased from the CA3/CAl border toward the subiculum. By contrast, in the longitudinal axis, each segment of the CAl region responded at a shorter latency to stimulation of a given rostrocaudal level of the mEC. Septal CAl levels responded at shorter latencies to caudal mEC stimulation sites while more temporal CAl levels responded at shorter latencies to rostral mEC stimulation sites. When stimulated at threshold stimulation intensity, the initial CAl response propagated to the rest of the CAl field with a conduction velocity of 0.5–0.9 m/s.

These results suggest that the associative pathways linking CA3 and CA1 regions can transmit mEC‐elicited DG activities to large segments of the hippocampal formation while preserving the topographical relationship between the mEC and the hippocampus in the time domain. These findings are in contrast to the so‐called lamellar hypothesis. © 1994 Wiley‐Liss, Inc.
Model of local connectivity patterns in CA3 and CA1 areas of the hippocampus
Authors: Bernard Christophe , Wheal Howard V.
Published: May 2005

In this study we describe a model of connectivity linking the different neurons in the CA3 and CA1 areas of the young male rat hippocampus. The anatomical and electrophysiological values of the parameters used in the model were selected from the available literature. Each type of synapse was characterized by its spatial location on the dendritic tree, its weight, its probability of activation, and the ionotropic receptors involved. We have shown that the degree of convergence and divergence of inputs is highly dependent upon the type of neuron and its spatial location. The different gradients of connectivity we describe support the lamellar hypothesis from a functional point of view, even if the anatomical patterns seem diffuse. The analysis of the proportion of common afferents to a class of neurons further confirmed this point. It is suggested that the circuitry creates local coherence in terms of processing of information by establishing restricted areas where information is preferentially treated. The functional consequences and limitations of these findings are also discussed. This model is the first step in the development of a network model of the hippocampus with realistic architecture. © 1994 Wiley‐Liss, Inc.
Dendritic Ca2+ accumulations and metabotropic glutamate receptor activation associated with an n‐methyl‐d‐aspartate receptor‐independent long‐term potentiation in hippocampal CA1 neurons
Authors: Petrozzino Jeffrey J. , Connor John A.
Published: May 2005

Bathing hippocampal slices in the potassium channel blocker tetraethylammonium (TEA), while stimulating the Schafer collaterals at a low frequency, induces Ca2+ ‐dependent, N‐methyl‐D‐aspartate (NMDA) receptor‐independent long‐term potentiation of synaptic transmission (LTPk) in CA1 neurons. We have combined ratio imaging of fura‐2 and mag‐fura‐5 in hippocampal CA1 neurons with intracellular and field recordings to evaluate postsynaptic Ca2+ changes that occur in the induction of LTPk. Test stimuli were applied at 0.05 Hz to stratum radiatum in the presence of the NMDA receptor antagonists D, L‐2‐amino‐5‐phosphonovaleric acid (100μM) or MK‐801 (10μM). During TEA exposure (15–25 mM; 10 min), cells fired prolonged action potentials both spontaneously and in response to test stimuli resulting in transient, micromolar Ca2+ accumulations in both somata and dendrites. The initial EPSP slope, measured 60 min after TEA wash‐out, was potentiated to approximately 200% of control. The Ca2+ channel blocker nimodipine (10 μM) greatly reduced Ca2+ transients in both magnitude and duration and prevented LTPk induction. Pretreatment of slices with compounds that block metabotropic glutamate receptor (mGluR)‐stimulated phosphoinositide hydrolysis, L‐2‐amino‐3‐phosphonopropionic acid (L‐AP3, 50‐200 μM) or L‐aspartate‐β‐hydroxamate (50–100 μM), as well as protein kinase C (PKC) inhibitors (sphingosine, 20 μM; RO‐31‐8220, 0.2 μM; or calphostin C, 2 μM) also blocked LTPk. Ca2+ transients were unaffected by L‐AP3 or RO‐31‐8220. These findings suggest that Ca2+ influx through voltage‐gated channels and co‐activation of PKC by mGluRs are both necessary for induction of LTPk. Activation of mGluRs must also occur in NMDA receptor‐dependent induction paradigms, but is possibly of lesser importance owing to the much greater gating of Ca2+ directly into the dendritic spines. © 1994 Wiley‐Liss, Inc.
“Short‐stops” in rats with fimbria‐fornix lesions: Evidence for change in the mobility gradient
Authors: Whishaw Ian Q. , Cassel Jean‐Christophe , Majchrzak Monique , Cassel Suzanne , Will Bruno
Published: May 2005

Rats with damage to the hippocampal formation and allied structures are hyperactive in many test situations but the cause of this hyperactivity is not known. Here the activity of control rats and rats with fimbria‐fornix lesions is documented in tests of overnight activity. Details of activity are then characterized from video recordings of behavior in an open field. Rats with fimbria‐fornix lesions make significantly more stops of shorter duration and thus more individual trips than control rats but they do not differ in the distance traveled on individual trips or in travel speed. It is suggested that the main difference between fimbria‐fornix rats and control rats is that when fimbria‐fornix rats stop they remain “still” for shorter durations than do control rats. This finding is discussed in relation to a theory of locomotor/exploratory behavior, and in relation to its implications with respect to the performance of fimbria‐fornix rats in studies of learning and memory. © 1994 Wiley‐Liss, Inc.
Correlation of anoxic neuronal responses and calbindin‐D28k localization in stratum pyramidale of rat hippocampus
Authors: Morris Mary E. , Baimbridge Kenneth G. , El‐Beheiry Hossam , Obrocea Gabriela V. , Rosen Andrei S.
Published: May 2005

Immunohistochemical staining for the calcium‐binding protein calbindin‐D28k (CaBP) was combined with Lucifer Yellow (LY) identification and intracellular recording of changes in membrane parameters of pyramidal neurons in CA2, CA1, and the sebiculum of rat hippocampal slices during brief exposure (4.0 ± 0.19 min) to N2. Anoxia evoked either a depolarization or hyperpolarization of membrane potential (VM) (+21.5 ± 2.79 mV above VM = −70.5 ± 1.50 mV, n = 30 and −7.2 ± 0.72 mV below VM = −68.2 ± 1.34 mV, n = 24, respectively) and a fall in membrane resistance of =20%. Differences in the response could be correlated with the presence or absence of CaBP and the localization of neurons in different layers of stratum pyramidale and sectors of the hippocampus. For neurons immunopositive for calbindin (CaBP(+)), depolarization was observed more frequently (83%) than hyperpolarization (17%); in contrast, 44% of responses of calbindin‐negative (CaBP(−)) neurons were depolarizing and 56% were hyperpolarizing. Depolarizations of CaBP(+) neurons were more gradual in slope, and more rapidly reached a plateau in comparison with those recorded in CaBP(−) neurons. Responses of neurons in the superficial layer of stratum pyramidale (in which 79% of CaBP(+) pyramidal neurons were situated) were mainly depolarizing (91%), while for those in the deep layer (which contained 89% of the CaBP(−) cells) such responses were observed less often (45%). Depolarization was also more common than hyperpolarization for cells located in CA2/CA1c/CA1b (63%) than in the CA1a/subicular region (37%). The depolarizing response of the majority of pyramidal neurons which are CaBP(+), superficial, and closer to CA3 may reflect an efficient buffering of intracellular Ca2+, which maintains a low [Ca2+]i, steep gradient for Ca2+ influx and may facilitate the movement of Ca2+ away from points of entry. The neurons which are CaBP(−), deep, and closer to subiculum and in which N2 evokes hyperpolarization, on the other hand, may have a sustained elevation/accumulation of cytosolic Ca2+ which could activate K+ conductance, inhibit Ca2+ influx, and stabilize the membrane potential. These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+ homeostasis and the determination of selective neuronal vulnerability. © 1995 Wiley‐Liss, Inc.
Reduction of the threshold for long‐term potentiation by prior theta‐frequency synaptic activity
Authors: Christie Brain R. , Stellwagen David , Abraham Wickliffe C.
Published: May 2005

Activation of the lateral perforant path input to the dentate gyrus with theta‐patterned conditioning trains produced LTP of synaptic efficacy that changed in magnitude as an inverted U‐shaped function of the number of trains. The LTP induction function was not fixed, however, and could be shifted to the left by administering 5 Hz “priming” stimulation to the lateral path 10 min prior to the conditioning trains. The priming effect was input specific and selective to a narrow window of stimulus frequencies. The shift to the left of the LTP induction function by priming stimulation was blocked by the muscarinic receptor antagonist atropine sulphate. Nimodipine, an antagonist of L‐type voltage‐sensitive calcium channels, did not mimic the priming effect but instead produced a general facilitation of LTP is induction. These data demonstrate that the degree to which LTP is induced in the lateral path is a non‐linear function of afferent activity, and that this function, including LTP threshold, can be shifted to the left by prior synaptic activity at hippocampal theta‐rhythm frequencies. © 1995 Wiley‐Liss, Inc.
Adenosine antagonists have differential effects on induction of long‐term potentiation in hippocampal slices
Authors: Forghani Reza , Krnjević K.
Published: May 2005

How adenosine leakage and tetanic release might affect long‐term potentiation (LTP) was investigated by applying adenosine antagonists 8(p‐sulfophenyl)theophylline (8SPT) or 8‐cyclopentyl‐3, 7‐dihydro‐1, 3‐dipropyl‐1H‐purine‐2, 6‐dione (DPCPX) to slices, while recording CA1 field EPSPs and population spikes. In the first series of experiments, we applied weak double tetani (at 100 Hz, for 1 s) that were subliminal for evoking LTP in initial control runs. In the presence of 8SPT—at concentrations (10–50 μM) which block both A1 and A2 receptors—the same tetani consistently evoked LTP of population spikes but not of excitatory postsynaptic potentials (EPSPs), whereas DPCPX (50 nM), which blocks only A1 receptors, facilitated LTP of both EPSPs and population spikes. These results are consistent with previous evidence that tetanic adenosine release on the one hand depresses LTP via A1 receptors but on the other facilitates LTP via A2 receptors.

In a second set of experiments, 8SPT (50–100 μM) did not prevent the induction of LTP of both EPSPs and population spikes by stronger tetanic stimulation. Therefore A2 receptor activation is not essential for the induction of LTP when stronger tetani are applied. Overall, the main effect of endogenous adenosine release is to oppose LTP induction. © 1995 Wiley‐Liss, Inc.
Hippocampal long‐term potentiation does not affect either discrimination learning or reversal learning of the rabbit nictitating membrane response
Authors: Rioux George F. , Robinson Gilbert B.
Published: May 2005

The theoretical premise that the acquistion and storage of information occurs through the strengthening of synaptic connections has contributed to the popularity of long‐term potentiation (LTP) as a candidate neural mechanism for associative learning. However, whether experimentally induced LTP facilitates, disrupts, or has no effect on subsequent learning is a controversial issue. The present study examined the reported facilitative effect of LTP within hippocampal perforant path‐dentate gyrus synapses on subsequent discriminative conditioning of the rabbit nictitating membrane response. In addition, the effect of LTP on subsequent reversal learning of the initial discrimination was examined. LTP did not significantly affect acquisition of the initial discriminative response or subsequent reversal learning. Furthermore, the magnitude of LTP could not be used to predict the rate of acquisition of either task. The failure to find an effect of LTP on classical conditioning of the rabbit nictitating membrane response mirrors the recent failures to replicat the disruptive effect of LTP on spatial learning in the rat. Thus, the potential contribution of an LTP‐like mechanism to associative learning remains equivocal. © 1995 Wiley‐Liss, Inc.
Simulation of spatial learning in the Morris water maze by a neural network model of the hippocampal formation and nucleus accumbens
Authors: Brown Michael A. , Sharp Patricia E.
Published: May 2005

Cells in the hippocampal formation show spatial firing correlates thought to be critical to the role played by this structure in spatial learning. Place cells in the hippocampus proper show location‐specific activity, whereas cells in the postsubiculum fire as a function of momentary directional heading.

One question which has received little attention is how these spatial signals are used by motor structures to actually guide spatial behavior.

Here we present a model of how one kind of spatial behavior, instrumental learning in the Morris water maze, could be guided by the spatial information in the hippocampal formation. For this, we concentrate on the hippocampal projection to the nucleus accumbens, which is strongly implicated in instrumental learning.

In the model, simulated firing patterns of place cells and head direction cells activate “motor” cells in the “accumbens.” Each motor cell causes a particular locomotor movement in a simulated rat. In this way, the “rat” locomotes through the simulated environment. Each step places the animal in a slightly different location and directional orientation, which, in turn, activates a different set of place and head direction cells, thus causing the next locomotor response, and so on. Connection strengths between cells are initially set randomly. When the animal encounters the reward location, however, connections are altered, so that recently active synapses are strengtheened. Thus, successful moves in a particular locational and directional context are “stamped in.”

Simulated rats show rapid learning, similar in many ways to that of actual rats. In particular, they generate efficient routes to the goal after minimal experience, and can do so from somewhat novel starting positions.

Consideration of the model architecture shows that (1) combined use of directional and place information is an example of a linearly inseparable problem and that (2) some types of novel route generation, often thought to require a “cognitive mapping” strategy, can be generated from the S‐R type model used here. © 1995 Wiley‐Liss, Inc.
Effect of adenosine on bicuculline‐resistant paired‐pulse inhibition in the rat hippocampal slice
Authors: Higgins Michael J. , Stone Trevor W.
Published: May 2005

This study extends previous investigations into the effect of adenosine on bicuculline‐resistant paired‐pulse inhibition between field potentials evoked 300 ms apart in the CA1 area of the rat hippocampal slice. A direct assessment of the effect of adenosine on paired‐pulse inhibition is complicated by the facts that adenosine directly depresses evoked potentials and bicuculline‐resistant paired‐pulse inhibition is greather between pairs of small potentials than between pairs of larger potentials. Adenosine increased biculline‐resistant paired‐pulse inhibition when stimulus strength was constant between adenosine and control but paired‐pulse inhibition of responses in adenosine was markedly less than paired‐pulse inhibition of control responses of the same size. Futhermore, adenosine decreased the size of conditioned potentials to a significantly lesser extent than unparired potentials of the same initial size. Taken together the results indicate that adenosine can decrease bicuculline‐resistant paired‐pulse inhibition in the hippocampus. A possible mechanism for this effect is that adenosine is suppressing transmission at excitatory terminals onto interneurones which would suggest that these receptors are more sensitive to adenosine than those on the Schaffer collateral/CA1 pyramidal cell synapses. In this case adenosin should reduce paired‐pulse inhibition at lower concentrations than are required for depression of single evoked potentials. A comparison of the concentration‐response relationships for the effects of adenosine on paired‐pulse inhibition and on single evoked potentials ruled out greater sensitivity of adenosine receptors at excitatory terminals onto interneurones as an explanation for adenosine's action on bicuculline‐resistant paired‐pulse inhibition. Adenosine was less effective at reducing inhibition evoked by large supramaximal conditioning stimuli than by submaximal for evoked potential size, although control paired‐pulse inhibiton is larger in the later case. This finding is consistent with adenosine reducing bicuculline‐resistant paired‐pulse inhibition by causing an increase in simultaneous paired‐pulse facilitation. © 1995 Wiley‐Liss, Inc.