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Learning and memory of cue-reward association meaning by modifications of synaptic efficacy in dentate gyrus and piriform cortex.

This article begins with a review of recent experiments investigating the synaptic efficacy changes occurring in rat dentate gyrus and piriform cortex during an associative olfactory task. In all these experiments, animals were trained to discriminate among an artificial cue, a patterned electrical stimulation distributed to the lateral olfactory tract associated with a water reward, and a natural odor associated with a flash of light. Monosynaptic field potential responses evoked by single electrical stimuli to the lateral olfactory tract were recorded in the ipsilateral piriform cortex before and just after each training session. Monosynaptic field and polysynaptic field potentials evoked by single electrical stimuli applied respectively to the lateral perforant pathway and lateral olfactory tract were also recorded in ipsilateral dentate gyrus. The results showed an increase in synaptic efficacy subsequent to the first training session in the dentate gyrus network when compared with piriform cortex at the later stage of the learning. The early increase of monosynaptic response in the dentate gyrus was observed immediately after the first learning session but disappeared 24 h later. Inversely, a synaptic depression developed across sessions, becoming significant at the onset of the last (fifth) session. The polysynaptic potential recorded in this structure increased substantially when rats began to discriminate the leaming cues, usually after the second or third learning session. Then, from the third to the fifth session, an LTP like-phenomenon appeared in piriform cortex when rats perfectly mastered the associations. Experiments using high-frequency stimulation to prevent changes in gyrus dentatus indicated that the onset of the observed depression was necessary for the learning of the olfactory associations. The fact that hippocampal and cortical neuronal networks exhibited different timing in synaptic efficacy changes could physiologically explain learning and memory processes.

Animals↗

Effects of serotonin on the intrinsic membrane properties of layer II medial entorhinal cortex neurons.

Although serotonin (5-HT) is an important neuromodulator in the superficial layers of the medial entorhinal cortex (mEC), there is some disagreement concerning its influences upon the membrane properties of neurons within this region. We performed whole cell recordings of mEC Layer II projection neurons in rat brain slices in order to characterize the intrinsic influences of 5-HT. In current clamp, 5-HT evoked a biphasic response consisting of a moderately short latency and large amplitude hyperpolarization followed by a slowly developing, long lasting, and small amplitude depolarization. Correspondingly, in voltage clamp, 5-HT evoked a robust outward followed by a smaller inward shift of holding current. The outward current evoked by 5-HT showed a consistent current/voltage (I/V) relationship across cells with inward rectification, and demonstrating a reversal potential that was systematically dependent upon the extracellular concentration of K(+), suggesting that it was predominantly carried by potassium ions. However, the inward current showed a less consistent I/V relationship across different cells, suggesting multiple independent ionic mechanisms. The outward current was mediated through activation of 5-HT(1A) receptors via a G-protein dependent mechanism while inward currents were evoked in a 5-HT(1A)-independent fashion. A significant proportion of the inward current was blocked by the I(h) inhibitor ZD7288 and appeared to be due to 5-HT modulation of I(h) as 5-HT shifted the activation curve of I(h) in a depolarizing fashion. Serotonin is thus likely to influence, in a composite fashion, the information processing of Layer II neurons in the mEC and thus, the passage of neocortical information via the perforant pathway to the hippocampus.

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

Morphological evidence for altered synaptic organization and structure in the hippocampal formation of seizure-sensitive gerbils.

Seizure-sensitive (SS) and seizure-resistant (SR) Mongolian gerbils were used for three experiments. In the first experiment, GABAergic neurons and terminals in the dentate gyrus were localized with GAD immunocytochemistry. GAD-positive puncta adjacent to cell bodies of GABAergic pyramidal basket cells were counted in light microscopic preparations. The pyramidal basket cells of SS gerbils displayed a significant threefold increase in the number of GAD-positive puncta associated with their cell bodies as compared to those from SR gerbils. These data indicate that the number of GABAergic synapses with pyramidal basket cell bodies in the dentate gyrus was greater in SS gerbils. An electron microscopic (EM) analysis of GAD immunocytochemical preparations showed GAD-positive axon terminals forming symmetric synapses with GAD-positive basket cell bodies. However, numerous terminals forming symmetric axosomatic synapses with basket cells were not immunopositive, and other synapses formed by terminals were not classified because reaction product in the cell bodies obscured postsynaptic densities. Therefore, routine EM preparations were analyzed for symmetric and asymmetric axosomatic synapses on pyramidal basket cells and granule cells of SS and SR gerbils. The data obtained from these preparations showed that the pyramidal basket cells of SS gerbils had a selective increase in the number of symmetric synapses per 10 microns of soma as compared to those of the SR gerbils. In contrast, the granule cells did not show any significant difference in the number of either symmetric or asymmetric axosomatic synapses between SS and SR gerbils. These results indicate that pyramidal basket cell bodies of SS gerbils have more inhibitory synapses than do those of SR gerbils. The third experiment used SS gerbils with lesions of the perforant pathway that stopped seizure activity (Ribak, C. E., and S. U. Khan (1987) The effects of knife cuts of hippocampal pathways on epileptic activity in the seizure-sensitive gerbil. Brain Res. 418:251-260). The percentage of axon terminal area occupied by synaptic vesicles and their packing density was determined in CA3 mossy fiber boutons and compared for lesioned and nonlesioned SS gerbils. The mossy fibers of nonlesioned SS gerbils showed a depletion of synaptic vesicles consistent with the previous results of Peterson et al. (Peterson, G. M., C. E. Ribak, and W. H. Oertel (1985) A regional increase in the number of hippocampal GABAergic neurons and terminals in the seizure-sensitive gerbil. Brain Res. 340:384-389).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Principal cells are the postsynaptic targets of supramammillary afferents in the hippocampus of the rat.

Neurons of the supramammillary nucleus are known to fire phase-locked to hippocampal theta rhythm. Stimulation of this area induces theta activity in the hippocampus via the medial septum and facilitates perforant pathway stimulation-evoked population spikes in the dentate gyrus even if the medial septum is inactivated. This latter effect was suggested to be due to a direct inhibitory input from the supramammilary nucleus to hippocampal nonpyramidal cells resulting in disinhibition. In the present study, using anterograde tracing with Phaseolus vulgaris leucoagglutinin, we aimed to identify the types of neurons innervated by the supramammillary projection in the dentate gyrus and Ammons horn, with particular attention to the presumed postsynaptic inhibitory neurons, which may mediate the proposed disinhibitory action. Double-immunostaining for the tracer and different neuropeptides (somatostatin, cholecystokinin, neuropeptide Y) or calcium binding proteins (calretinin, parvalbumin, calbindin D28K) present in different subpopulations of interneurons revealed no multiple contacts between supramammillary afferents and labeled inhibitory cells at the light microscopic level. Furthermore, postembedding immunostaining of electron microscopic sections for GABA demonstrated that none of the 68 PHAL-labeled supramammillary boutons examined and none of their postsynaptic targets were immunoreactive for the inhibitory neurotransmitter. We conclude, therefore, that most if not all postsynaptic targets of the supramammillary projection are principal cells both in the dentate gyrus and in the CA2-CA3a subfields. This suggests that a mechanism other than disinhibition is responsible for the facilitatory effect of this pathway on hippocampal evoked activity.

Afferent Pathways↗

Activation of somatostatin-synthesizing neurons in the hippocampal formation through kindling-induced seizures.

The present study was designed to determine if and to what extent somatostatin (SST) synthesizing neurons of the hippocampal formation are activated during seizures, elicited through kindling of the perforant pathway. Tissue was used and analyzed from animals which had experienced a single after discharge, or a stage 3 or stage 5 seizure. The protein expression of the oncogene c-fos in activated, depolarizing neurons was utilized to identify seizure-activated SST-synthesizing neurons. Combined immunocytochemical and in situ hybridization methods were used to identify these double-labeled, Fos protein, and SST mRNA-containing neurons. The results were quantified and compared across seizure stages. The resulting data demonstrate that at every stage of seizure development, a majority of SST-synthesizing neurons is activated, but that these activated SST mRNA-containing neurons represent only a minority of all seizure-activated, Fos-expressing neurons in the hippocampal formation. The data further reveal a numerical hierarchy in which the majority of double-labeled neurons is present in the hilus of the dentate, followed by the stratum oriens of CA1. It is concluded that SST-synthesizing neurons represent an integral component of the kindling activated neuronal network and, since the SST synthesizing neurons represent the minority of all seizure-activated neurons in the hippocampal formation, that this neuronal network is likely to be of considerable neurochemical complexity.

Animals↗

AMPA-selective glutamate receptor subtype immunoreactivity in the hippocampal formation of patients with Alzheimer's disease.

Immunocytochemical techniques were employed in order to examine the distribution and relative intensity of the AMPA receptor subunits GluR1 and GluR2/3 within the hippocampal formation of normal controls and Alzheimer's disease (AD) cases. Throughout our investigation we examined cases exhibiting a wide range of pathologic severity, thus allowing us to correlate our immunohistochemical data with the extent of pathology. Specifically, we investigated the distribution of these receptor subunits in hippocampal sectors that are particularly vulnerable to AD pathology (i.e., CA1 and subiculum) and compared these findings with those obtained following examination of sectors that are generally resistant to pathologic change (i.e., CA2/3, dentate gyrus). Within vulnerable sectors we observed a variable loss of GluR1 and GluR2/3 immunolabeling. The degree to which these proteins were reduced appeared to correlate with the extent of neurofibrillary pathology and cell loss. Despite the loss of labeled cells, the intensity of immunolabeling within the remaining neurons was comparable with, and in many instances even greater than, that observed in control cases. Within resistant sectors, the distribution of immunoreactive elements was comparable in both case groups yet the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular layer of the dentate gyrus and in the stratum lucidum of CA3 (i.e., the termination zones of perforant pathway and mossy fibers). In addition, within AD cases dramatic increases were observed within the supragranular and polymorphic layer of the dentate gyrus (i.e., the terminal zones of sprouting mossy fiber collaterals). The increase in GluR1 and GluR2/3 immunolabeling is hypothesized to occur in response to the deafferentation of selected glutamatergic pathways. Moreover, our data support that hippocampal plasticity is preserved, even in severe AD cases, and suggest a critical role for AMPA receptor subunits in this plasticity and in maintaining hippocampal functioning.

Aged↗

mRNA differential display reveals Krox-20 as a neural plasticity-regulated gene in the rat hippocampus.

The prolonged maintenance of hippocampal long-term potentiation depends on de novo protein and RNA synthesis, indicating an involvement of altered gene expression in long-lasting plastic changes in synaptic efficacy. We have used an mRNA differential display technique to identify a set of genes that are induced by neural activity in the rat hippocampus. Sixteen independent cDNAs were isolated whose mRNA level was markedly modulated by convulsive seizure. One of these encodes Krox-20, a zinc finger DNA binding protein. High frequency tetanic stimulation of perforant pathway, which elicited a persistent long-term potentiation (>10 h), rapidly induced expression of krox-20 mRNA in the hippocampus of urethane-anesthetized rat. The increase in krox-20 mRNA was transient and NMDA receptor-dependent. These results suggest a role for krox-20 in the maintenance of long-term potentiation.

Amino Acid Sequence↗

Distribution of glutamate receptor subunit NMDAR1 in the hippocampus of normal elderly and patients with Alzheimer's disease.

Immunocytochemical techniques were employed to study the distribution and cytological features of NMDAR1-immunoreactive elements in the human hippocampal formation. Subjects with Alzheimer's disease (AD), presenting with a wide range of neuropathology and classified into six Braak stage (I-VI), and nondemented age-matched controls were examined. In control cases, the most intense NMDAR1 immunoreactivity was observed within the soma and dendrites of granule cells in the dentate gyrus and pyramidal neurons in Ammon's horn. Whereas small variations in the pattern of immunoreactivity were noted in control cases, AD subjects were characterized with intersubject variability which in most instances correlated with neuropathologic severity. For example, AD cases, particularly those with mild/modest pathology (Braak I-III), were indistinguishable from controls in the overall pattern of immunolabeling. In contrast, in those more severe AD cases (Braak IV-VI) the intensity of immunolabeling within the CA fields was greater than observed in controls and those with mild AD pathology. In addition, in pathologically severe cases numerous NMDAR1-positive pyramidal neurons were characterized by unique morphologic features including long and often tortuous apical dendrites. These latter findings were most prevalent in the CA1 region and subiculum. In contrast to the marked increase in immunolabeling in the CA fields, in the dentate gyrus we observed a reduction in NMDAR1 labeling particularly within the outer molecular layer (i.e., termination zone of the perforant pathway). This latter region was also the site of a number of NMDAR1-labeled plaques. Notably, the overall pattern of NMDAR1 immunoreactivity is distinct from that observed with antibodies against AMPA receptor subunits and suggests a differential role of various inotropic glutamate receptors in hippocampal plasticity in AD.

Aged↗

Abolition of CA1 population spike by sensory stimulation.

The effect of sensory stimulation, such as stroking of the animals' fur, on activation of the hippocampal CA1 field was studied in paralyzed and locally anaesthetized rats. CA1 population responses evoked either monosynaptically (ipsilateral CA3 stimulation) or trisynaptically (perforant pathway stimulation) decreased markedly when sensory stimulation was applied, and CA1 population spikes were absent during most periods of sensory stimulation. These results demonstrate the strong modulatory role of sensory inputs on hippocampal circuits.

Animals↗

Projections from the presubiculum and the parasubiculum to morphologically characterized entorhinal-hippocampal projection neurons in the rat.

The relations between the inputs from the presubiculum and the parasubiculum and the cells in the entorhinal cortex that give rise to the perforant pathway have been studied in the rat at the light microscopical level. Projections from the presubiculum and the parasubiculum were labeled anterogradely, and, in the same animal, cells in the entorhinal cortex that project to the hippocampal formation were labeled by retrograde tracing and subsequent intracellular filling with Lucifer Yellow. The distribution and the number of appositions between the afferent fibers and hippocampal-projection neurons in the various layers of the entorhinal cortex were analyzed. The results show that layers I-IV of the entorhinal cortex contain neurons that give rise to projections to the hippocampal formation. The morphology of these projection neurons is highly variable and afferents from the presubiculum and the parasubiculum do not show a preference for any specific morphological cell type. Both inputs preferentially innervate the dendrites of their target cells. However, presubicular and parasubicular projections differ with respect to the layer of entorhinal cortex they project to. The number of appositions of presubicular afferents with cells that have their cell bodies in layer III of the entorhinal cortex is 2-3 times higher than with cells in layer II. In contrast, afferents from the parasubiculum form at least 2-3 times as many synapses on the dendrites of cells located in layer II than on neurons that have their cell bodies in layer III. Cells in layers I and IV of the entorhinal cortex receive weak inputs from the presubiculum and parasubiculum. Not only is the presubiculum different from the parasubiculum with respect to the distribution of projections to the entorhinal cortex, they also differ in their afferent and efferent connections. In turn, cells in layer II of the entorhinal cortex differ in their electrophysiological characteristics from those in layer III. Moreover, layer II neurons give rise to the projections to the dentate gyrus and field CA3/CA2 of the hippocampus proper, and cells in layer III project to field CA1 and the subiculum. Therefore, we propose that the interactions of the entorhinal-hippocampal network with the presubiculum are different from those with the parasubiculum.

Animals↗

Action of norepinephrine in the dentate gyrus. II. Iontophoretic studies.

The effects of iontophoretic application of 1-norepinephrine (NE) and related drugs on granule cell responses evoked by a stimulus pulse applied to the medial perforant pathway were studied in anesthetized rats. Drugs were applied and responses recorded at successive dorso-ventral positions along the dendrites and at the cell body layer. 1. Reciprocal actions of alpha and beta receptors were revealed in the cell body region. The beta agonist isoproterenol decreased the population spike while the beta antagonist sotalol increased it. In contrast, the alpha agonists phenylephrine and clonidine increased the population spike whereas the alpha antagonist prazosin decreased it. The action of the drugs was rapid, dose dependent and reversible. NE itself had no effect when applied in the granule cell layer. 2. In contrast to the failure of NE to elicit a short term response, and in confirmation of a previous report (Neuman and Harley 1983), the prolonged application of NE in the granule cell layer produced a longterm enhancement of the population spike. However, this effect was also observed after the application of d-NE. 3. NE affected granule cell responses in the middle third of the dendrites where it reduced the evoked synaptic potential (ESP, current flow produced by excitatory synaptic activity) in a dose-dependent manner. Recordings taken simultaneously in the cell body region revealed a reduction of the population spike and no change in the ESP at the cell body layer (the positive-going ESP reflecting an outward current flow from the cell). In an attempt to delineate receptor specificity, a series of alpha and beta agonists and antagonists were applied to the mid-dendritic region. All drugs reduced the ESP in a manner similar to NE. Such lack of specificity in the action of NE has been previously reported in the spinal motoneuron (Engberg et al. 1976; Marshall 1983). The function of NE in the dentate gyrus is discussed in the light of these and previous results.

Animals↗

The gamma subunits of the native GABAA/benzodiazepine receptors.

Subunit-specific antibodies to all the gamma subunit isoforms described in mammalian brain (gamma(1), gamma(2S), gamma(2L), and gamma(3) have been made. The proportion of GABA(A) receptors containing each gamma subunit isoform in various brain regions has been determined by quantitative immunoprecipitation. In all tested regions of the rat brain, the gamma(1) and gamma(3) subunits are present in considerable smaller proportion of GABA(A) receptor than the gamma(2) subunit. Immunocytochemistry shows that gamma(1) immunoreactivity concentrates in the stratum oriens and stratum radiatum of the CA1 region of the hippocampus. In the dentate gyrus, gamma(1) immunoreactivity concentrates on the outer 2/3 of the molecular layer coinciding with the localization of the axospinous synapses of the perforant pathway. In contrast, gamma(3) immunoreactivity concentrates on the basket cells and other GABAergic local circuit neurons of the hilus. These cells are also rich in gamma(2S). In the cerebellum, gamma(1)++ immunolabeling was localized on the Bergmann glia. The gamma(2S) and gamma(2L) subunits are differentially expressed in various brain regions. Thus the gamma(2S) is highly expressed in the olfactory bulb and hippocampus whereas the gamma(2L) is very abundant in inferior colliculus and cerebellum, particularly in Purkinje cells, as immunocytochemistry, in situ hybridization and immunoprecipitation techniques have revealed. The gamma(2S) and gamma(2L) coexist in some brain areas and cell types. Moreover, the gamma(2S) and gamma(2L) subunits can coexist in the same GABA(A) receptor pentamer. We have shown that this is the case in some GABA(A) receptors expressed in cerebellar granule cells. These GABA(A) receptors also have alpha and beta subunits forming the pentamer. Immunoblots have shown that the rat gamma(1), gamma(2S), gamma(2L) and gamma(3) subunits are peptides of 47, 45, 47 and 44 kDa respectively. Results also indicate that there are aging-related changes in the expression of the gamma(2S) and gamma(2L) subunits in various brain regions which suggest the existence of aging-related changes in the subunit composition of the GABA(A) receptors which in turn might lead to changes in receptor pharmacology. The results obtained with the various gamma subunit isoforms are discussed in terms of the high molecular and binding heterogeneity of the native GABA(A) receptors in brain.

Aging↗

AMPA-selective glutamate receptor subtype immunoreactivity in the hippocampal dentate gyrus of patients with Alzheimer disease. Evidence for hippocampal plasticity.

Immunocytochemical techniques were employed in order to examine the distribution and relative intensity of immunolabeling of the alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) receptor subunits GluR1 and GluR2/3 within the hippocampal formation of patients with Alzheimer disease (AD). Within sectors of the hippocampus that are particularly vulnerable to AD pathology (i.e., CA1, subiculum), we observed a variable loss of GluR1 and GluR2/3 immunolabeling correlating with the extent of cell loss and neurofibrillary pathology. In contrast, in less vulnerable sectors of the hippocampus (i.e., CA2/3, dentate gyrus), the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular and polymorphic layers of the dentate gyrus. Importantly, these latter regions correspond to termination zones of glutamatergic perforant pathway axons and mossy fiber collaterals, respectively. The increase in immunolabeling within these projection fields is hypothesized to occur in response to the deafferentation of selected glutamatergic pathways, and suggests a critical role for AMPA receptor subunits in hippocampal plasticity.

Aged↗

Molecular analysis of the function of the neuronal growth-associated protein GAP-43 by genetic intervention.

GAP-43 is a presynaptic membrane phosphoprotein that has been implicated in both the development and the modulation of neural connections. The availability of cDNA clones for GAP-43 makes it possible to examine with greater precision its role in neuronal outgrowth and physiology. We used Northern blots and in situ hybridization with GAP-43 antisense RNA probes to show that GAP-43 is expressed selectively in associative regions of the adult brain. Immunocytochemical analyses showed alterations in the pattern of GAP-43 expression in the hippocampus during reactive synaptogenesis following lesions of the perforant pathway. Genetic intervention methodology was used to analyze the molecular nature of GAP-43 involvement in synaptic plasticity. GAP-43-transfected PC12 cells displayed an enhanced response to nerve growth factor, suggesting that GAP-43 may be directly involved in neurite extension and in the modulation of the neuronal response to extrinsic trophic factors. Studies of PC12 cell transfectants, in which the synthesis of GAP-43 was blocked by expression of GAP-43 antisense RNA, showed that evoked dopamine release was significantly attenuated in these cells. The use of gene transfer into neurons with the HSV-1 vector is presented as a method of analyzing the interaction of GAP-43 with signal transduction systems during neurotransmitter release.

Animals↗

Site and time dependent effects of acute stress on hippocampal long-term potentiation in freely behaving rats.

The phasic effects of stress-induced elevations of corticosterone on long-term potentiation (LTP) were investigated in the hippocampus of awake, freely behaving rats. Field potential recordings were performed in the dentate gyrus with stimulation of the medial perforant pathway or the CA1 with stimulation of the commissural/associational pathway, on the contralateral hemisphere. LTP was induced either shortly (1 h) after acute stress or 4 h later. Animals were either adrenalectomized or adrenally intact. A subgroup of animals were injected with a low dose of dexamethasone 4 h prior to the stressor, in order to suppress the corticosterone response to restraint stress, and they were tested for LTP in the dentate gyrus 4 h after the stressor. In the dentate gyrus, stress had no effect on LTP induction at 1 h post-stress; however, it produced a significant suppression at the 4 h interval. As expected, adrenalectomized rats did not show stress-suppression of LTP, but showed a lower level of LTP with or without stress. Supporting a role of stress-induced glucocorticoid secretion in LTP suppression, dexamethasone treatment of adrenally intact animals blocked the acute stress suppression of LTP in the dentate gyrus. In the CA1 field, restraint stress did not significantly affect LTP induction at either the 1- or 4-h post-stress intervals. Similarly, stress by itself, did not significantly affect neuronal excitability in either the dentate gyrus or CA1 hippocampal field at either the 1- or 4-h post-stress interval. The present results suggest that stress affects synaptic plasticity differently at the two hippocampal subfields and that the effects are time-dependent and involve the stress-induced surge of glucocorticoids.

Acute Disease↗

Changes in synaptic membrane phosphorylation after tetanic stimulation in the dentate area of the rat hippocampal slice.

Slices of rat brain hippocampus were stimulated electrically in the perforant pathway. After electrical stimulation, known to produce long-lasting post-tetanic potentiation, endogenous phosphorylation of membrane proteins was measured in a crude mitochondrial fraction, prepared from stimulated and unstimulated slices. Tetanic stimulation specifically enhanced the incorporation of [32P]phosphate into a protein band with apparent molecular weight of 50K. When the same number of pulses were given, but at a much slower rate (1 pulse per 4 sec instead of 15 pulses per sec) no posttetanic stimulation and concomitantly, no enhanced incorporation of [32P]phosphate were observed into the 50K band. When the stimulation of the slices was performed in Ca2+-free medium, again no potentiation and no enhanced incorporation into the 50K protein band were observed. It is suggested that electrical stimulation enhances the activity of the protein kinase that phosphorylates the 50K protein.

Animals↗

Effect of 5-HT depletion of the hippocampus on neuronal transmission from perforant path through dentate gyrus.

Stimulation of the perforant pathway (pp) elicits a characteristic evoked action potential (EAP) in the granule cell layer of the dentate gyrus. The EAP was recorded in rats depleted of hippocampal serotonin (5-HT) by prior injection of p-chloroamphetamine (PCA) or 5,7-dihydroxy-tryptamine (5,7-DHT) as well as in untreated animals during two behavioral states, slow-wave sleep (SWS) and still-alert behavior (SAL). As reported previously, in untreated rats the amplitude of the EAP response was significantly greater during SWS than SAL. Stimulation of the median raphe nucleus (MR) prior to stimulating the pp (prestimulation) augmented the EAP response, but only during SWS. In contrast, in animals injected with PCA or 5,7-DHT there was no difference of the amplitude of the EAP during SWS and SAL. However, the augmentation of the EAP during SWS produced by prestimulation of the median raphe was still present. It is concluded that 5-HT innervation of the dentate gyrus may be involved in the behavioral modulation of the EAP response. Modulation of the EAP following prestimulation of the MR appears to be effected by a non-serotonergic input to the dentate gyrus originating in, or coursing through, the median raphe.

5,7-Dihydroxytryptamine↗

Dentate granule cells in the rat hippocampal formation have the behavioral characteristics of theta neurons.

Recordings were made from the dentate gyrus granule cell layer of freely-moving rats. The neurons recorded from the layer were divisible into 3 classes using a combination of electrophysiological and behavioral criteria; the duration of the extracellularly recorded unfiltered action potential provided the most reliable means of differentiating between cell types. Class I and class II neurons always fired in short duration single action potentials, while class III neurons had broader waveforms and occasionally were observed to fire complex spikes. As the most obvious behavioral correlate of class I and class II neurons was movement of the rat, these cells correspond to the theta cells of Ranck. Class III neurons for which a behavioral correlate was observed had the characteristics of the place cells described by O'Keefe. The neurons of classes I and II comprised 89% (56 of 63) of the total population sampled in the granule cell layer. Most of these neurons (49 of 56) discharged at short latency in response to a stimulus delivered via the perforant pathway; in contrast, none of the class III neurons observed were activated in this way. Horseradish peroxidase or Fast Green dye ejection through glass microelectrodes recording class I cell activity in urethane-anesthetized animals revealed the electrode tip to be in the granule cell layer in 27 of 27 cases. Six single class I neurons were also antidromically activated by a stimulus from an electrode placed in the hippocampal mossy fibers, and collision testing was successful in all cases. It is concluded that the dentate granule cells are theta cells.

Animals↗