Localization of enkephalin and cholecystokinin immunoreactivities in the perforant path terminal fields of the rat hippocampal formation

The distribution of enkephalin immunoreactivity (EI) in the molecular layer of the hippocampal formation corresponded to the terminal field of the lateral perforant path and the lateral temporoammonic tract. The distribution of cholecystokinin immunoreactivity (CI) in the molecular layer of the hippocampal formation corresponded to the established terminal field of the medial temporoammonic tract. The exception was a CI band at the deep part of the molecular layer throughout the regio superior. Accordingly, an additional terminal field of the medial temporoammonic tract is suggested. Selective lesion of the entorhinal afferents to the hippocampus and the area dentata resulted in a disappearance of EI throughout the molecular layer with no affection of CI and vice versa. Neonatally X-ray irradiated hippocampi were examined as they appear in the adult animal. These animals are known to possess an altered relation between the granule cells of area dentata and the perforant path zones extending beyond a reduced medial blade into the stratum oriens of the regio inferior. In such animals EI and CI revealed the same pattern of changes by following the perforant path zones into stratum oriens due to neonatal X-ray irradiation. Accordingly, the perforant path may contain EI and CI independent of the granule cell dendrites. Based on a discussion of these observations we conclude that enkephalin immunoreactivity is localized in terminals of the lateral perforant path and the lateral temporoammonic tract and that cholecystokinin immunoreactivity is localized in the terminals of the medial perforant path and the medial temporoammonic tract.     

Septotemporal distribution of entorhinal projections to the hippocampus in the cat: electrophysiological evidence

The projection of the entorhinal cortex (EA) to the hippocampus in the cat has been studied by electrophysiological methods. Field potentials elicited by EA stimulation sites were measured in the hippocampus (fascia dentata). Different topographic distributions of the amplitude and of the onset latency of average evoked potentials (AEPs) were obtained depending on the place of the stimulation along a lateromedial axis in the Ea. The lateral EA elicited the largest AEPs in the septal part of the hippocampus and the medial EA evoked maximal responses in the temporal part of the hippocampus, while the intermediate part of the EA evoked the largest AEPs in the splenial (intermediate) part of the hippocampus. Unit activity elicited by hippocampal stimulation was measured in the EA. Analysis of the antidromic unit activity showed that the pathways analysed were monosynaptic. Different conduction velocities to the septal part of the hippocampus were found; the pathway from the lateral EA was the fastest and the pathway from the medial EA the slowest. Assuming that the sites of maximal AEP amplitude correspond to the location of the major synaptic inputs, it can be concluded that the active synaptic inputs arising along a latero-medial axis in the EA are distributed within the hippocampus according to a septotemporal axis, although with some overlap between the different projections. Therefore it may be concluded that the hippocampus is not homogeneous with respect to the inputs from the EA. The present observations are discussed regarding anatomical data and putative functional differences between septal and temporal hippocampus.     

Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat

The Projections o the entorhinal and perirhinal cortices to the hippocampus in the cat have been studied with retrograde and anterograde tracing techniques. Retarogradely transported tracers, which were injected at different levels along the septotemporal longitudinal hippocampal axis, result in labeled neurons in superficial entorhinal cortical layers II and III. Occasionally, labeled cells were also observed in the deepest entorhinal layer as well as in the superficial layers of the perirhinal area 35. It could further be shown that labeled neurons located superficially in the entorhinal cortex corresponds to a septotemporal gradient along the longitudinal axis of the hippocampus. This topographical organization of the entorhinal-hippocampal projection system could be substantiated by the use of anterograde tracing of radioactively labeled amino acids. Injections in the entorhinal cortex produce labeled fibers in the hippocampus. Injections in the perirhinal area 35 result also in labeling over the hippocampus, whereas area 36 does not seem to distribute fibers to the hippocampus. As anticipated from the results of the retrograde tracing experiments, injections located laterally, in or close to the posterior rhinal sulcus, produce prominent labeling over the septal pole of the hippocampus, whereas progressively more medially located injections result in progressively more temporally located labeling. This topographical distribution of perforant path fibers along the septotemporal axis of the hippocampus, which is related to a lateromedial axis in the entorhinal cortex, has been observed following injections in the lateral entorhinal area (LEA) as well as in the medial entorhinal area (MEA). The present observations are discussed in regard of other connectional and putative functional differences between the septal and temporal hippocampus.     

Spatiotemporal analysis of NO production upon NMDA and tetanic stimulation of the hippocampus

Nitric oxide (NO) is a gaseous neuromessenger. Although increasing evidence reveals significant physiological effects of NO in the hippocampal synaptic plasticity, the spatial distribution of NO production has remained largely uncharacterized due to the poor development of techniques for real-time NO imaging. In this work, using a NO-reactive fluorescent dye, diaminorhodamine-4M (DAR-4M), time-dependent heterogeneous NO production is demonstrated in hippocampal slices upon N-methyl-D-aspartate (NMDA) stimulation or tetanic stimulation. NMDA-induced DAR fluorescence increase in the CA1 was found to be twice that in the CA3 and the dentate gyrus (DG). Intracellular Ca(2+) concentration was also investigated. NMDA induced similar Ca(2+) responses both in the CA1 and DG, which were approx. 13% greater than that in the CA3. Subsequently, spatial distribution of NO production in the CA1 upon a tetanic stimulation of Schaffer collateral was investigated, because there are contradictory reports on the effect of NO on long-term potentiation (LTP), and that NO is known to exert various physiological effects depending on its concentration. In the stratum radiatum (sr), DAR fluorescence increase upon tetanus was largest at the vicinity of a stimulating electrode and decreased as a function of increasing distance from the stimulating electrode, suggesting the possibility that the effect of NO in LTP is dependent on the distance between stimulating and recording electrodes. The tetanus-induced Ca(2+) response observed in the sr showed the same but weak distant dependence from the stimulating electrode. Taken together, the observed heterogeneity in the distribution of NO production is suggestive of region-specific effects of NO in the hippocampus.     

Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex.

The topographic and laminar organization of entorhinal projections to the dentate gyrus, hippocampus, and subicular complex was investigated in the Macaca fascicularis monkey. Injections of 3H-amino acids were placed at various positions within the entorhinal cortex and the distribution of anterogradely labeled fibers and terminals within the other fields of the hippocampal formation was determined. Injections of the retrograde tracers Fast blue, Diamidino yellow, and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were also placed into the dentate gyrus, hippocampus, and subicular complex, and the distribution of retrogradely labeled cells in the entorhinal cortex was plotted using a computer-aided digitizing system. The entorhinal cortex gave rise to projections that terminated in the subiculum, in the CA1, CA2, and CA3 fields of the hippocampus, and in the dentate gyrus. Projections to the dentate gyrus, and fields CA3 and CA2 of the hippocampus, originated preferentially in layers II and VI of the entorhinal cortex whereas projections to CA1 and to the subiculum originated mainly in layers III and V. Anterograde tracing experiments demonstrated that all regions of the entorhinal cortex project to the outer two-thirds of the molecular layer of the dentate gyrus and to much of the radial extent of the stratum lacunosum-moleculare of CA3 and CA2. While the terminal distributions of entorhinal projections to the dentate gyrus, CA3, and CA2 were not as clearly laminated as in the rat, projections from rostral levels of the entorhinal cortex preferentially innervated the outer portion of the molecular layer and stratum lacunosum-moleculare, whereas more caudal levels of the entorhinal cortex projected relatively more heavily to the deeper portions of the entorhinal terminal zones. The entorhinal projection to the CA1 field of the hippocampus and to the subiculum followed a transverse rather than radial gradient of distribution. Rostral levels of the entorhinal cortex terminated most heavily at the border of CA1 and the subiculum. More caudal levels of the entorhinal cortex projected to progressively more distal portions of the subiculum (towards the presubiculum) and more proximal portions of CA1 (towards CA2). Lateral portions of the entorhinal cortex projected to caudal levels of the recipient fields and more medial parts of the entorhinal cortex projected to progressively more rostral portions of the fields.     

c-fos protooncogene expression in rat hippocampus and entorhinal cortex following tetanic stimulation of the perforant path.

The elevated expression of the c-fos protooncogene has been proposed to be a marker of cell activation leading to a long term cellular response. In this communication we compared the c-fos mRNA accumulation in the hippocampus (i.e. postsynaptic cells) and entorhinal cortex (i.e. presynaptic cells) following high (tetanic) and low frequency electrical stimulation of the perforant path. Using Northern blot analysis we have found that high frequency stimulation elevates c-fos expression in both hippocampus and entorhinal cortex, and the increase of c-fos mRNA levels in the entorhinal cortex is less pronounced, but longer lasting, than in the hippocampus. Slight increase of c-fos mRNA levels has been also observed in low frequency treated animals in the entorhinal cortex, but not in the hippocampus. These findings raise the question about differences in mechanisms involved in c-fos activation in both parts of the brain after stimulation which evokes long term potentiation (LTP) of synaptic efficacy.     

Binding of [125I]insulin to specific receptors and stimulation of nucleotide incorporation in cells cultured from rat brain

The occurrence of insuling receptors and biological responses to insulin has been investigated in trypsin-dissociated fetal rat brain cells maintained in culture for 8 days. Binding of [¹²⁵]insulin to brain cells in culture was time- and pH-dependent and 85–90% specific. Porcine insulin competed for [¹²⁵]insulin binding in a dose-dependent manner. Unrelated polypeptides, including angiotensin II, glucagon, bovine growth hormone, and bovine prolactin did not compete for [¹²⁵]insulin binding. The half-life of [¹²⁵]insulin dissociation from receptors at 24°C was 15 min and a plot of ln[B/Bo] vs time suggested two dissociation rate constants of2.7 × 10⁻⁴ sec⁻¹ and5.0 × 10⁻⁵ sec⁻¹. Scatchard analysis of the binding data gave a curvelinear plot which may indicate negative cooperativity or the occurrence of both high affinity(K_a = 2 × 10¹¹M⁻¹) and low affinity(K_a = 4 × 10¹⁰M⁻¹) sites. Of the estimated total of 4.9 × 10⁴ binding sites per cell, 28–30% appear to be high affinity sites.

Incubation of cultures with insuling caused a time- and dose-dependent stimulation of [³H]thymidine and [³H]uridine incorporation into TCA-precipitable material. Maximum stimulation of thymidine incorporation (2–5-fold) occured 11 h after incubation with 167 nM insulin. The same concentration of insulin caused a 2.2-fold increase in [³H]uridine incorporation in 2 h. These results indicate that cells cultured from rat brain contain specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis in the central nervous system.     

Adenosine-induced suppression of synaptic responses and the initiation and expression of long-term potentiation in the CA1 region of the hippocampus

The results of several previous studies have suggested that pretreatment with adenosine can block the induction of long-term potentiation (LTP), although other studies have found no effect of adenosine on the induction of LTP. The interaction of adenosine with the induction of LTP in the rat hippocampal slice was investigated. Inhibition of synaptic responses by adenosine either prior to or immediately after high-frequency or theta-burst stimulation did not affect LTP measured after washout of the adenosine. The only conditions under which adenosine blocked the development of LTP was when it was given 3–5 minutes prior to the stimulation train. To understand how it was possible to induce LTP, during the period 1–3 minutes following adenosine when synaptic responses were virtually eliminated, evoked responses during the 100 Hz stimulation train were recorded. Although synaptic responses to low-frequency stimulation were virtually eliminated by adenosine, they reappeared during high-frequency stimulation. These results suggest that although adenosine can depress synaptic responses, an increase in neurotransmission during a high-frequency train can partially overcome this effect of adenosine, and the hypothesis that adenosine can selectively block LTP is not supported.     

c-fos Protooncogene expression in rat hippocampus and entorhinal cortex following tetanic stimulation of the perforant path

The elevated expression of the c-fos protooncogene has been proposed to be a marker of cell activation leading to a long term cellular response. In this communication we compared the c-fos mRNA accumulation in the hippocampus (i.e. postsynaptic cells) and entorhinal cortex (i.e. presynaptic cells) following high (tetanic) and low frequency electrical stimulation of the perforant path. Using Northern blot analysis we have found that high frequency stimulation elevates c-fos expression in both hippocampus and entorhinal cortex, and the increase of c-fos mRNA levels in the entorhinal cortex is less pronounced, but longer lasting, than in the hippocampus. Slight increase of c-fos mRNA levels has been also observed in low frequency treated animals in the entorhinal cortex, but not in the hippocampus. These findings raise the question about differences in mechanisms involved in c-fos activation in both parts of the brain after stimulation which evokes long term potentiation (LTP) of synaptic efficacy.     

Localization and quantitation of dynorphin B in the rat hippocampus

The present study measures the content of dynorphin B in the rat hippocampus, and localizes the dynorphins within the intrinsic hippocampal neuronal circuitry. The level of dynorphin B, which is representative of the prodynorphin-derived peptides, was markedly depleted by intrahippocampal injection of colchice, which destroyed the great majority of the hippocampal granule cells and the associated mossy fiber pathway. The hippocampus contralateral to the injection demonstrated a slight, non-significant rise in dynorphin B levels after colchicine. Entorhinal cortical lesions ablating the perforant pathway input to the hippocampus did not significantly alter dynorphin B levels in the hippocampus. Unilateral fimbrial transection caused a small but significant increase in dynorphin B on the side of the lesion relative to the unlesioned side, but neither side was significantly different from control.     

Low-frequency stimulation induces a new form of LTP, metabotropic glutamate (mGlu5) receptor- and PKA-dependent, in the CA1 area of the rat hippocampus

Low frequency-induced short-term synaptic plasticity was investigated in hippocampal slices with 60-electrode recording array. Remarkably, the application of low-frequency stimulation (1 Hz) for a short duration (3-5 min) resulted in the induction of a slow-onset long-term potentiation (LTP) in the immediate vicinity of the stimulated electrode. This phenomenon was observed exclusively in the CA1 subfield, neither in the CA3 area nor in the dentate gyrus. The induction of this slow-onset LTP required neither N-methyl-D-aspartate (NMDA) nor non-NMDA ionotropic receptor activation but was strongly dependent on metabotropic glutamate mGlu(5) receptor stimulation and [Ca(2+)]i increase. In addition, this form of synaptic plasticity was associated with an increase in cAMP concentration and required protein kinase A activation. Paired-pulse facilitation ratio and presynaptic fiber volley amplitude were unaffected when this LTP was triggered, suggesting the involvement of postsynaptic modifications. Although mitogen activated protein kinase pathway was stimulated after the application of low frequency, the induction and maintenance of this slow-onset LTP were not dependent on the activation of this intracellular pathway. The direct activation of adenylyl cyclase with forskolin also induced a synaptic enhancement displaying similar features. This new form of LTP could represent the mnesic engram of mild and repetitive stimulation involved in latent learning.     

Spontaneous and synaptic input from granule cells and the perforant path to dentate basket cells in the rat hippocampus

To characterize excitatory inputs to dentate basket cells from dentate granule cells and the perforant path, the whole-cell recording technique was used in neonatal rat hippocampal slices. Spontaneous excitatory input to basket cells was also examined and compared to that of other interneurons in the dentate gyrus. Basket cells were separable from other neurons in the dentate gyrus based on morphology and location, as determined by biocytin staining following recording, and by resting membrane potential, propensity to fire action potentials spontaneously, and miniature excitatory postsynaptic current (EPSC) characteristics. Minimal electrical stimulation of the granule cell layer evoked in basket cells short latency EPSCs that were composed of both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) components as judged by their time course, voltage dependence, and blockade by selective antagonists. Perforant path EPSCs exhibited slower kinetics than EPSCs evoked by granule cell stimulation. Like granule cell evoked EPSCs, however, perforant path EPSCs were composed of both NMDA and AMPA components. Minimal electrical stimulation of the granule cell layer and perforant path evoked monosynaptic EPSCs in only 67% and 62% of the trials, respectively, suggesting that these inputs are as unreliable as previously determined inputs from CA3 pyramidal cells (48%). Tetrodotoxin-insensitive spontaneous miniature EPSCs were frequent in basket cells and non-basket interneurons residing either at the border between the granule cell layer and the hilus or deep within the hilus. Miniature EPSCs recorded from all cells held at ?70 mV were blocked completely by 3 μSM 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX). Though a component of the miniature EPSCs recorded from border and deep hilar interneurons at +40 mV was blocked by the NMDA receptor antagonist D -2-amino-phosphonovaleric acid (D-APV), miniature EPSCs in basket cells were insensitive to D-APV. We conclude that input from granule cells and the perforant path results in activation of basket cells via glutamatergic synapses that employ both NMDA and AMPA receptors. These inputs to basket cells likely contribute to feedback and feedforward inhibition of granule cells. The absence of an NMDA receptor component in spontaneous miniature EPSCs of dentate basket cells implies a difference in organization of excitatory synapses made onto basket cells compared with other hilar interneurons. © 1995 Wiley-Liss, Inc.     

Effects of chemical and surgical lesions on levels of chromatographically identified enkephalin-like peptides in rat hippocampus

The present study quantitates the content of Met- and Leu-enkephalin in the rat hippocampus, and provides information on the localization of the enkephalins within the hippocampal neuronal circuitry. Several enkephalins were identified in rat hippocampus, two of which are shown to be Met- and Leu-enkephalin. The levels of these enkephalins, and of other unidentified enkephalin-related peptides, were not depleted by intrahippocampal colchicine, which destroyed the great majority of the hippocampal granule cells and the associated mossy fiber pathway. Entorhinal cortical lesions ablating the perforant pathway input to the hippocampus also did not significantly lower enkephalin levels in the hippocampus. Unilateral fimbrial transection caused a significant bilateral increase in both Met- and Leu-enkephalin levels. This may result from loss of a stimulatory input to putative enkephalin containing interneurons within the hippocampus. The extents of all lesions were verified histologically in hippocampi used for biochemical analysis. No evidence was seen for the presence of enkephalins in the perforant pathway, nor in nerve fibers in the fimbria/fornix, which provide the other main source of hippocampal efferents. The enkephalins are likely to be intrinsic to the hippocampus, in which neuronal cell bodies containing enkephalin-like immunoreactivity have been extensively reported.     

Septal modulation of the population spike in the fascia dentata produced by perforant path stimulation in the rat

Electrical stimulation of the perforant path, which originates in the entorhinal cortex, produces a characteristic excitatory postsynaptic field potential (extracellular EPSP) which can be recorded in the fascia dentata. This evoked response may include a population spike, if stimulation is sufficient. In the anaesthetized rat, stimulation of the medial septum, when paired with perforant path stimulation, was found to augment the population spike component of the evoked field potential. Stimulation of the septum alone produced no apparent field potential. The augmentation effect was found to have a rapid onset (4 ms), which is sufficient for the participation of interneurons, and a relatively long time course (150 ms). Presynaptic mechanisms of facilitation were ruled out as there was no concurrent alteration of the extracellular EPSP. A change in population spike threshold, compatible with a postsynaptic mechanism, was observed and some possible models of action discussed. Augmentation survived depletion of hippocampal norepinephrine caused by injections of 6-hydroxydopamine into the dorsal noradrenergic bundle, indicating that the facilitation was not due to an activation of the ascending noradrenergic fibres of passage originating from the locus coeruleus. The cholinergic septo-hippocampal pathway was ruled out as a likely candidate for the modulation as the augmentation survived injections of the muscarinic antagonists atropine and scopolamine and the nicotinic antagonists tubocurarine and dihydro-beta-erythroidine. A relationship between the septal modulation and hippocampal theta was suggested.     

Effects of norepinephrine and serotonin upon spontaneous activity and responses to mossy fiber stimulation of CA3 neurons in hippocampal slices

Effects of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) upon spontaneous activity and responses to mossy fiber stimulation (mfs) were tested in 192 units of the field CA3 in the guinea pig and rat hippocampal slices. The drugs were added to the incubating medium or ejected by pressure from a micropipette. After NE superfusion firing rate increased in 52% of the reactive units, while activity of 48% was suppressed. The direction of the effect strongly correlated with pattern of spontaneous activity: only the cells with 'complex discharges' (short bursts of 2-4 spikes with attenuation of amplitude) were suppressed by NE; the cells with single spikes increased the level of activity. Similar excitatory effects of NE were observed in all units (n = 14) with single spike activity recorded in the field CA1. 5-HT increased activity in 30% of the reactive units and suppressed it in 70% of them. Some of the cells which were suppressed by 5-HT, were excited by NE. In more than a half of the units tested, 5-HT led to prolonged (up to 30-40 min) increase of the level of background activity irrespective of the initial excitatory or suppressive action; periodic grouped discharges appeared in some units under the influence of 5-HT. The response to mfs usually changed in the same direction as the level of background activity during application of NE and 5-HT, though some exceptions were observed in both cases. Prolonged (up to 30-40 min) facilitation of responses to mfs was present after application of 5-HT.     

The role of the direct perforant path input to the CA1 subregion of the dorsal hippocampus in memory retention and retrieval

Subregional analyses of the hippocampus have suggested a selective role for the CA1 subregion in intermediate/long-term spatial memory and consolidation, but not short-term acquisition or encoding processes. It remains unclear how the direct cortical projection to CA1 via the perforant path (pp) contributes to these CA1-dependent processes. It has been suggested that dopamine selectively modulates the pp projection to CA1 while having little to no effect on the Schaffer collateral (SC) projection to CA1. This series of behavioral and electrophysiological experiments takes advantage of this pharmacological dissociation to demonstrate that the direct pp inputs to CA1 are critical in CA1-dependent intermediate-term retention and retrieval function. Here we demonstrate that local infusion of the nonselective dopamine agonist, apomorphine (10, 15 microg), into the CA1 subregion of awake animals produces impairments in between-day retention and retrieval, sparing within-day encoding of a modified Hebb-Williams maze and contextual conditioning of fear. In contrast, apomorphine produces no deficits when infused into the CA3 subregion. To complement the behavioral analyses, electrophysiological data was collected. In anesthetized animals, local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the more proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in the EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a more fundamental role for EC-CA1 synaptic transmission in terms of intermediate-term, but not short-term spatial memory.     

Opposing effects of oxytocin and of a μ-receptor agonistic opioid peptide on the same class of non-pyramidal neurones in rat hippocampus

A study was made of the effects of opioid peptides on the spontaneous firing of oxytocin-responsive non-pyramidal neurones in hippocampal slices. D-Ala2-Gly-ol5-enkephalin (DAGO), a mu-opiate agonist, decreased or even suppressed the firing of these neurones, an effect reversed by naloxone. In contrast, U-50,488, a kappa-opiate agonist, had no effect. When the slices were synaptically uncoupled by elevating the concentration of external magnesium, oxytocin still excited non-pyramidal neurones and DAGO still inhibited them. Thus, opiates and oxytocin exerted direct, opposite effects on the same population of neurones, which apparently bear mu-type receptors. An indirect action of opioids on the excitability of pyramidal cells was apparent and is probably mediated by the same interneurones, since the amplitude of the depolarizing component of the synaptic potential elicited by stimulation of Schaffer's collaterals was increased in the presence of DAGO.     

An analysis of entorhinal cortex projections to the dentate gyrus,hippocampus, and subiculum of the neonatal macaque monkey

The entorhinal cortex is the primary interface between the hippocampal formation and neocortical sources of sensory information. Although much is known about the cells of origin, termination patterns, and topography of the entorhinal projections to other fields of the adult hippocampal formation, very little is known about the development of these pathways, particularly in the human or nonhuman primate. We have carried out experiments in which the anterograde tracers ³H‐amino acids, biotinylated dextran amine, and Phaseolus vulgaris leucoagglutinin were injected into the entorhinal cortex in 2‐week‐old rhesus monkeys (Macaca mulatta). We found that the three fiber bundles originating from the entorhinal cortex (the perforant path, the alvear pathway, and the commissural connection) are all established by 2 weeks of age. Fundamental features of the laminar and topographic distribution of these pathways are also similar to those in adults. There is evidence, however, that some of these projections may be more extensive in the neonate than in the mature brain. The homotopic commissural projections from the entorhinal cortex, for example, originate from a larger region within the entorhinal cortex and terminate much more densely in layer I of the contralateral entorhinal cortex than in the adult. These findings indicate that the overall topographical organization of the main cortical afferent pathways to the dentate gyrus and hippocampus are established by birth. These findings add to the growing body of literature on the development of the primate hippocampal formation and will facilitate further investigations on the development of episodic memory. J. Comp. Neurol. 522:1485–1505, 2014. © 2013 Wiley Periodicals, Inc.     

Repeated administration of pentylenetetrazol alters susceptibility of rat hippocampus to primed-burst stimulation: evidence from in vitro study on CA1 of hippocampal slices

The effectiveness of θ pattern primed-bursts (PBs) on development of primed-burst (PB) potentiation was investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the hippocampal slices from control and kindled rats at two post-kindling periods, i.e. 48–144 h (early phase) and 30–33 days (long-lasting phase). Field potentials (population excitatory post-synaptic potential, pEPSP) were recorded at stratum radiatum following stimulation of the stratum fibers. θ pattern primed-bursts were delivered to stratum radiatum and PB potentiation was assessed. The results showed that 48–144 h after kindling, PB potentiation in CA1 of kindled slices is significantly greater than control slices. In contrast, 30–33 days after kindling PB potentiation was not observed and the pEPSP slope was depressed after PBs delivery, which lasted at least 60 min. Our results suggest that shortly after kindling, PB potentiation can be more readily induced while one month later, it is more difficult to elicit. These findings may help to explain the behavioral deficits seen with the kindling model of epilepsy.