Hippocampal Efferents Research Articles

Sex-specific dendritic morphology of hippocampal pyramidal neurons in the adolescent and young adult rats.

CA1 and CA3 pyramidal neurons are the major sources of hippocampal efferents. The structural features of these neurons are presumed to be involved in various normal/abnormal cognitive and emotional outcomes by influencing the pattern of synaptic inputs and neuronal signal processing. Although many studies have described hippocampal structure differences between males and females, these reports mainly focused on gross anatomical features in adult or aged models, and such distinctions on neuronal morphology and dendritic spine density during adolescence, a period of high vulnerability to neurodevelopmental disorders, have received much less attention. In this work, we analyzed dendritic architecture and density of spines in CA1 and CA3 neurons of male and female rats in early adolescence (postnatal day, PND 40) and compared them with those in late adolescence/young adulthood (PND 60). On PND 40, CA1 neurons of male rats showed more Sholl intersections and spine density in apical and basal dendrites compared to those in females. The Sholl intersections in basal dendrites of CA3 neurons were also more in males, whereas the number of apical dendrite intersections was not significantly different between sexes. In male rats, there was a notable decrease in the number of branch and terminal points in the basal dendrite of CA1 neurons of young adults when compared to their sex-matched adolescent rats. On the other hand, CA1 neurons in young adult females also showed more Sholl intersections in apical and basal dendrites compared to adolescent females. Meanwhile, the total cable length, the number of branches, and terminal points of apical dendrites in CA3 neurons also exhibited a significant reduction in young adult male rats compared to their sex-matched adolescents. In young adult rats, both apical and basal dendrites of CA3 neurons in males showed fewer intersections with Sholl circles, but there were no significant differences in dendritic spine density or count estimation between males and females. On the other hand, young adult female rats had more Sholl intersections and dendritic spine count on the basal dendrites of CA3 neurons compared to adolescent females. Although no significant sex- and age-dependent difference in neuronal density was detected in CA1 and CA3 subareas, CA3 pyramidal neurons of both male and female rats showed reduced soma area compared to adolescent rats. Our findings show that the sex differences in the dendritic structure of CA1 and CA3 neurons vary by age and also by the compartments of dendritic arbors. Such variations in the morphology of hippocampal pyramidal neurons may take part as a basis for normal cognitive and affective differences between the sexes, as well as distinct sensitivity to interfering factors and the prevalence of neuropsychological diseases.

Retrosplenial and subicular inputs converge on superficially projecting layer V neurons of medial entorhinal cortex

The medial entorhinal cortex (MEC) plays a pivotal role in spatial processing together with hippocampal formation. The retrosplenial cortex (RSC) is also implicated in this process, and it is thus relevant to understand how these structures interact. This requires precise knowledge of their connectivity. Projections from neurons in RSC synapse onto principal neurons in layer V of MEC and some of these neurons send axons into superficial layers of MEC. Layer V of MEC is also the main target for hippocampal efferents from the subiculum and CA1 field. The aim of this study was to assess whether the population of cells targeted by RSC projections also receives input from the hippocampal formation and to compare the distribution of synaptic contacts on target dendrites. We labeled the cells in layer V of MEC by injecting a retrograde tracer into superficial layers. At the same time, we labeled RSC and subicular projections with different anterograde tracers. 3D-reconstruction of the labeled cells and axons revealed likely synaptic contacts between presynaptic boutons of both origins and postsynaptic MEC layer V basal dendrites. Moreover, these contacts overlapped on the same dendritic segments without targeting specific domains. Our results support the notion that MEC layer V neurons that project to the superficial layers receive convergent input from both RSC and subiculum. These data thus suggest that convergent subicular and RSC information contributes to the signal that neurons in superficial layers of EC send to the hippocampal formation.

What the hippocampus tells the HPA axis: Hippocampal output attenuates acute stress responses via disynaptic inhibition of CRF+ PVN neurons

The hippocampus exerts inhibitory feedback on the release of glucocorticoids. Because the major hippocampal efferent projections are excitatory, it has been hypothesized that this inhibition is mediated by populations of inhibitory neurons in the hypothalamus or elsewhere. These regions would be excited by hippocampal efferents and project to corticotropin-releasing factor (CRF) cells in the paraventricular nucleus of the hypothalamus (PVN). A direct demonstration of the synaptic responses elicited by hippocampal outputs in PVN cells or upstream GABAergic interneurons has not been provided previously. Here, we used viral vectors to express channelrhodopsin (ChR) and enhanced yellow fluorescent protein (EYFP) in pyramidal cells in the ventral hippocampus (vHip) in mice expressing tdTomato in GABA- or CRF-expressing neurons. We observed dense innervation of the bed nucleus of the stria terminalis (BNST) by labeled vHip axons and sparse labeling within the PVN. Using whole-cell voltage-clamp recording in parasagittal brain slices containing the BNST and PVN, photostimulation of vHip terminals elicited rapid excitatory postsynaptic currents (EPSCs) and longer-latency inhibitory postsynaptic currents (IPSCs) in both CRF+ and GAD + cells. The ratio of synaptic excitation and inhibition was maintained in CRF + cells during 20 Hz stimulus trains. Photostimulation of hippocampal afferents to the BNST and PVN in vivo inhibited the rise in blood glucocorticoid levels produced by acute restraint stress. We thus provide functional evidence suggesting that hippocampal output to the BNST contributes to a net inhibition of the hypothalamic-pituitary axis, providing further mechanistic insights into this process using methods with enhanced spatial and temporal resolution.

Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition

Learning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and retrieval/expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we used an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory retrieval and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.

Activation Patterns in Superficial Layers of Neocortex Change Between Experiences Independent of Behavior, Environment, or the Hippocampus

Previous work suggests that activation patterns of neurons in superficial layers of the neocortex are more sensitive to spatial context than activation patterns in deep cortical layers. A possible source of this laminar difference is the distribution of contextual information to the superficial cortical layers carried by hippocampal efferents that travel through the entorhinal cortex and subiculum. To evaluate the role that the hippocampus plays in determining context sensitivity in superficial cortical layers, behavior-induced expression of the immediate early gene Arc was examined in hippocampus-lesioned and control rats after exposing them to 2 distinct contexts. Contrary to expectations, hippocampal lesions had no observable effect on Arc expression in any neocortical layer relative to controls. Furthermore, another group of intact animals was exposed to the same environment twice, to determine the reliability of Arc-expression patterns across identical contextual and behavioral episodes. Although this condition included no difference in external input between 2 epochs, the significant layer differences in Arc expression still remained. Thus, laminar differences in activation or plasticity patterns are not likely to arise from hippocampal sources or differences in external inputs, but are more likely to be an intrinsic property of the neocortex.

Selective deficits in spatial working memory in the neonatal ventral hippocampal lesion rat model of schizophrenia

The neonatal ventral hippocampal lesion (NVHL) manipulation is a neurodevelopmental animal model of schizophrenia that produces abnormalities in the prefrontal cortex and nucleus accumbens, both efferent targets of the hippocampus, and leads to spatial working memory impairments. To investigate the neuroanatomical basis of spatial working memory in NVHL animals, we assessed performance in two radial arm maze tasks known to be differentially sensitive to the two hippocampal efferent pathways, and measured levels of neuronal activation (Fos immunoreactivity [Fos-IR]) in the prefrontal cortex and nucleus accumbens following task performance. Neonatal rats (postnatal day 6–8) received excitotoxic lesions of the ventral hippocampus (n = 25), or a sham procedure (infusions of artificial cerebrospinal fluid; n = 22). Upon reaching adulthood, animals were trained in either a non-delayed random foraging task or a spatial delayed win-shift task. NVHL animals were impaired on the spatial delayed win-shift task, which depends on communication between hippocampus and prefrontal cortex, but were unimpaired on the non-delayed random foraging task, which requires connections between hippocampus and nucleus accumbens. Fos-IR in the nucleus accumbens was greater in NVHL animals than in shams following the random foraging task, despite similar levels of performance, while no group differences in Fos-IR in either the nucleus accumbens or prefrontal cortex were observed following win-shift performance. These results suggest that although the NVHL manipulation disrupts development of hippocampal efferents to both the prefrontal cortex and the nucleus accumbens, the disruption of hippocampal–prefrontal pathways has the dominant behavioral effect on spatial performance in NVHL rats.

Compensation in the neural circuitry of fear conditioning awakens learning circuits in the bed nuclei of the stria terminalis

The basolateral amygdala (BLA) is thought to be essential for fear learning. However, extensive training can overcome the loss of conditional fear evident following lesions and inactivation of the BLA. Such results suggest the existence of a primary BLA-dependent and a compensatory BLA-independent neural circuit. We tested the hypothesis that the bed nuclei of the stria terminalis (BST) provides this compensatory plasticity. Using extensive context-fear conditioning, we demonstrate that combined BLA and BST lesions prevented fear acquisition and expression. Additionally, protein synthesis in the BST was critical only for consolidation of BLA-independent but not BLA-dependent fear. Moreover, fear acquired after BLA lesions resulted in greater activation of BST regions that receive hippocampal efferents. These results suggest that the BST is capable of functioning as a compensatory site in the acquisition and consolidation of context-fear memories. Unlocking such neural compensation holds promise for understanding situations when brain damage impairs normal function or failure to regulate compensatory sites leads to anxiety disorders.

A behavioral analysis of the role of CA3 and CA1 subcortical efferents during classical fear conditioning.

It has been proposed that the hippocampus and subcortical structures interact during the processing of fear and anxiety-related information. It has been demonstrated that the subcortical efferents from CA3 and CA1 can be selectively disrupted without concomitant disruption to the afferents. The present experiment was designed to evaluate the role of CA3 efferents via the fimbria and the CA1 efferents via the dorsal fornix for encoding and consolidation/retrieval of classical fear conditioning. The present data suggest that the subcortical projections from CA3 and CA1 are differentially involved in the processing of classical fear conditioning, with CA3 subcortical efferents supporting acquisition of both cued and contextual fear but only supporting retention of contextual fear and CA1 subcortical efferents supporting the encoding and retrieval of both cued and contextual fear. These data further suggest that all hippocampal efferents are not homogeneous, and that the hippocampus and subcortex interact to process conditioned fear.

A double dissociation of subcortical hippocampal efferents for encoding and consolidation/retrieval of spatial information

CA3 lesions impair encoding, whereas CA1 lesions impair retrieval during learning of a Hebb-Williams maze. CA3 efferents in the fimbria were transected, taking care to spare cholinergic and GABAergic afferents. CA1 efferents in the dorsal fornix were similarly transected. Fimbria transections, but not dorsal fornix transections, resulted in deficits for the encoding of spatial information during learning of a Hebb-Williams maze. Dorsal fornix, but not fimbria, transections resulted in deficits for retrieval of spatial memory during learning of a Hebb-Williams maze. These results reveal a double dissociation for the roles of CA3 and CA1 subcortical efferents in encoding and retrieval processes that mirror the double dissociation seen after excitotoxic lesions of CA1 and CA3. These data provide support for the theory that the cholinergic projections from the septal nuclei modulate the dynamics for encoding and consolidation/retrieval in the hippocampus.

Temporal and spatial regulation of chondroitin sulfate, radial glial cells, growing commissural axons, and other hippocampal efferents in developing hamsters.

We investigated the time and space relationship between growth of hippocampal efferents, particularly those forming the hippocampal commissure, and expression of extracellular matrix components related to radial glial cells. Developing hamster brains from embryonic day (E) 13 to postnatal day (P) 7 had 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) crystals implanted into the hippocampus or were processed for fluorescent immunohistochemistry against chondroitin sulfate (CS) glycosaminoglycans and glial fibrillary acidic protein (GFAP). The first, pioneer fibers from the hippocampus were seen crossing the midline at E15 and arriving at the contralateral hippocampus 24-48 hours later (P1), followed closely by a thick front of growing fibers. Before E15, CS expression was preceded by septal fusion and was concomitant with formation of the commissural tract. On E15, CS expression formed a U-shaped border below the fimbria. From E15 to P3, CS became expressed between the hippocampal commissure and the third ventricle and at the caudal borders of the fornix columns. As the hippocampal commissure expanded, CS expression became gradually lighter to virtually disappear by P7. On E15 and P1, GFAP-positive radial glial cells were present caudal (but not rostral) to the commissure at the midline, partially overlapping CS expression. Similar cells were present dorsal to the fimbria, extending their processes perpendicularly over the growing axons. The data reveal that CS and radial glial cells form a tunnel surrounding the developing fimbria and a border at the midline caudal to the hippocampal commissure. It is suggested that these cellular and molecular borders play a role in guidance of hippocampal efferents.

Chapter 14 Character and function of specific neurons: a Cajalian perspective

Publisher Summary The chemical identification of neurons containing various neuroactive substances and calcium-binding proteins, together with modern tracing methods, confirm to a great extent Cajal's views on the target selectivity of particular cell types in various regions. The hippocampal efferents taking the fimbria route to reach the septum correspond to axons of pyramidal cells of the regio inferior (∼CA3-4), whereas those of the regio superior (∼CAl-2) have both, collateral and terminal branches ramifying in the plexi of the strata oriens, radiatum and lacunosum. Chandelier cells are immunoreactive to parvalbumin further characterized this singular short axon cell, in fact, the only type that escaped Cajal's observational powers. Concerning the intrinsic functional polarization of the neuron, Cajal's ideas, as in most instances, evolved in trying to incorporate his ever-increasing amount of observations. Thus, the so-called “law of dynamic polarization” gave way to the law of axipetal polarization, which included the possibility of propagation of the nerve impulse from the soma to the dendrite, as it occurs in the case of the axon originating from a dendrite at a considerable distance from the soma.

Long-term potentiation in the reciprocal corticohippocampal and corticocortical pathways in the chronically implanted, freely moving rat.

The hippocampus and adjacent cortical structures, including the entorhinal, perirhinal, and parahippocampal cortices, appear to serve as an integrated memory system. This extended hippocampal system is believed to influence memory and consolidation through an extensive set of reciprocal connections with widespread areas of the neocortex. Long-term potentiation (LTP) has been well-examined in the intrinsic connections of the hippocampus and neocortex. However, LTP in the pathways and structures thought to convey information between the hippocampus and neocortex has received little attention. If these pathways and structures are involved in information storage, and if LTP reflects a general synaptic encoding mechanism, then these systems are also likely to support LTP. In this paper we discuss a series of experiments aimed at investigating LTP in the efferents between the hippocampus and neocortex in chronically implanted animals. In the first experiment, the efferents of the perirhinal cortex were stimulated. LTP in the dentate gyrus (DG) reached asymptote more slowly than is typically seen following perforant path stimulation, whereas the frontal area (M1) reached asymptote more quickly than reported following corticocortical stimulation. The DG and M1 LTP was long-lasting, but entorhinal cortex LTP had decayed to baseline levels after a week. In the second experiment, the hippocampal efferents were stimulated. The perirhinal, entorhinal, and frontal cortex showed a similar slow potentiation, with only the perirhinal cortex levels returning to baseline after a week. In the third experiment, the projections from M1 were tested. The perirhinal cortex and hippocampus showed a long-lasting LTP. Although LTP was found in all pathways examined, there were differences in the induction and decay rate, and these properties may correspond to differences in learning rate and longevity of information storage.

Fimbria–fornix transection and excitotoxicity produce similar neurodegeneration in the septum

Fimbria–fornix transection produces neuronal injury in the septum. This cellular pathology is characterized by somatodendritic vacuolar abnormalities in neurons. Because these cellular changes are reminiscent of some of the morphological abnormalities seen with glutamate receptor-mediated excitoxicity, we tested whether excitotoxic injury to the septal complex of adult rats mimics the degeneration observed within the dorsolateral septal nucleus and medial septal nucleus following fimbria–fornix transection. The septal complex was evaluated at various time-points (6 h to 14 days) by light and electron microscopy following unilateral injection of the N-methyl- d-aspartate receptor agonist quinolinate or the non- N-methyl- d-aspartate receptor agonist kainate, and the morphological changes observed were compared to those abnormalities in the medial septal nucleus and dorsolateral septal nucleus at three to 14 days after fimbria–fornix transection. The patterns of cytoplasmic abnormalities and vacuolar injury were morphologically similar in the somatodendritic compartment of neurons following excitotoxicity and axotomy paradigms. These similarities were most evident when comparing the persistently injured neurons in the penumbral regions of the excitotoxic lesions at one to 14 days recovery to neurons in the medial septal nucleus and dorsolateral septal nucleus at seven and 14 days after fimbria–fornix transection. Pretreatment with the N-methyl- d-aspartate receptor antagonist dizocilpine maleate prior to unilateral fimbria–fornix transection attenuated the somatodentritic vacuolar damage found within the ipsilateral dorsolateral and medial septal nuclei at 14 days recovery. Because glutamate is the principal transmitter of hippocampal efferents within the fimbria–fornix, we conclude that postsynaptic glutamate receptor activation participates in the evolution of septal neuron injury following fimbria–fornix transection. Thus, excitotoxicity is a possible mechanism for transneuronal degeneration following central nervous system axotomy.

Ventral subiculum regulates hypothalamo–pituitary–adrenocortical and behavioural responses to cognitive stressors

The hippocampus plays an important role in central stress integration. The present study tests the hypothesis that the ventral subiculum, as a principal source of hippocampal efferents, is involved in co-ordination of hypothalamo–pituitary–adrenocortical and behavioural responses to cognitively-processed information. Basal hypothalamo–pituitary–adrenocortical activation appears to be normal in ventral subiculum lesion rats, as basal corticosterone and adrenocorticotropic hormone secretion, anterior pituitary pro-opiomelanocortin and type 1 corticotropin-releasing hormone receptor messenger RNA expression, adrenal and thymus weight, and splenic mitogen activity are not affected by lesion. Lesions of the ventral subiculum induce glucocorticoid hypersecretion following restraint stress or open field exposure, whereas responses to ether inhalation are unaffected. Interestingly, ventral subiculum lesion does not affect fast glucocorticoid negative feedback inhibition of restraint-induced adrenocorticotropic hormone release. Corticotropin-releasing hormone immunoreactivity is increased in the hypothalamic paraventricular nucleus of ventral subiculum rats, and is differentially depleted by acute stress exposure (relative to sham-lesion rats). However, ventral subiculum lesion does not affect basal and stress-induced corticotropin-releasing hormone, arginine vasopressin and cFOS messenger RNA expression in paraventricular nucleus neurons. Behavioural analysis reveals that ventral subiculum lesion rats are hyper-responsive to open field exposure, showing decreased total ambulation and reduced incidence of central square entry. The results suggest that the ventral subiculum plays a specific role in integrating cognitively-processed stimuli (e.g., restraint and open field exposure) into appropriate neuroendocrine and behavioural responses to stress. Enhanced stress-induced glucocorticoid secretion and increased corticotropin-releasing hormone biosynthesis are likely due to removal of oligosynaptic inhibitory input to the paraventricular nucleus subsequent to ventral subiculum lesion.

Selective forebrain fiber tract lesions implicate ventral hippocampal structures in tonic regulation of paraventricular nucleus corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression

The hippocampus appears to be involved in tonic regulation of the hypothalamo-pituitary-adrenocortical axis via interactions with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular nucleus (PVN). To further investigate the anatomical basis of such interactions, lesions were made to forebrain fiber tracts in position to communicate inhibitory information from the hippocampus to the PVN. Total fimbria-fornix transections (TFF) and lateral fimbria-fornix lesions (LFF) both significantly increased CRH mRNA levels in the medial parvocellular PVN, as assayed by semi-quantitative in situ hybridization histochemistry. Medial fimbria-fornix lesions or section of the medial corticohypothalamic tracts (MCHT) did not influence CRH mRNA levels. The LFF group showed increases in both AVP mRNA and ACTH secretion, whereas no other lesion was effective in this regard. The results suggest: (1) hippocampal efferents confering tonic inhibition of the HPA axis probably originate in regions contributing to the lateral extent of the fornix, representing structures in the ventral subiculum and ventral extent of CA1: (2) projections from the hippocampus to the medial basal hypothalamus (travelling in the MCHT) are unlikely to affect HPA function: (3) hippocampus may influence the PVN CRH/AVP neuron at multiple levels, in that LFF and TFF lesions have differential effects on PVN AVP mRNA levels and ACTH secretion.

Blockade of behavioral sensitization to methamphetamine by lesion of hippocampo-accumbal pathway

The present studies were carried out to explore a role of the hippocampal efferents in the development of the locomotor augmentation induced by repeated methamphetamine administrations. For this purpose, electrolytic lesions of either the dorsal fornix or the fimbria fornix were made bilaterally in rats. The latter treatment, not the former, blocked the behavioral sensitization. These results suggest that the hippocampo-accumbal pathway may play an important role in the development of the sensitization.

Electrophysiological analysis of the hippocampal output to the presubiculum

The hippocampal output to the dorsal presubiculum was analysed in the guinea-pig by field potential analysis. Perforant path volleys, synaptically elicited by stimulation of the dorsal psalterium of one side, were used to activate the lamellar circuit of the same side and, through interhippocampal impulses, the hippocampal pyramidal neurons of the opposite side. The discharge of the pyramidal neurons of the hippocampus was followed by a negative fast wave with associated unit firing in lamina principalis interna and in the innermost part of lamina principalis externa of the presubicular cortex. These findings suggested the generation of excitatory synaptic effects in lamina principalis interna and innermost lamina principalis externa. The presubicular response was present in preparations with the fornix bilaterally sectioned. It was eliminated by interruption of the caudally-directed hippocampal projections, which suggested that it was mediated by these hippocampal efferents. The generation site of the presubicular response in deep cell laminae was not consistent with the terminal field of the hippocampus-presubiculum projections but was with that of the subiculum-presubiculum projections. The hippocampal discharge evoked in the dorsal subiculum a response with shorter latency and lower threshold than the presubicular response. These data suggest that the presubicular response might be evoked through hippocampus-subiculum-presubiculum connections. The results show that the hippocampal output evokes excitatory synaptic effects in the presubiculum and that these effects are segregated in deep cell laminae. The fact that these laminae give origin to an important projection to the anterior thalamic nuclei suggests that hippocampal impulses may be transferred to subcortical structures through the presubiculum.

Electrophysiological analysis of the hippocampal projections to the entorhinal area

Responses evoked in the entorhinal area by impulse volleys originating in the ipsilateral hippocampus were analysed in the guinea-pig by means of field potential analysis. Perforant path volleys, synaptically elicited by stimulation of the dorsal psalterium of one side, were used to activate the hippocampal lamellar circuit of the same side and, through interhippocampal impulses, the hippocampal pyramidal neurons of the contralateral side. Discharge of the hippocampal pyramidal neurons was followed by a response, a fast negative deflection preceded and followed by slow waves, in the dorsal third of the ipsilateral entorhinal area. Laminar distribution of the fast negative deflection and of the time-locked unit activity suggested that excitatory synaptic effects followed by neuron discharge were generated in neurons of layers VI-II of the entorhinal area. The increasing latency of the fast negative deflection and of unit firing over the cortical depth suggested that these synaptic effects were generated in temporal sequence, going from layer VI to layer II. The entorhinal response disappeared after a lesion at the caudal border of the hippocampus interrupting the caudally-directed hippocampal efferents. The anatomy of the hippocampal and subicular projections to the entorhinal area in the guinea-pig, together with electrophysiological data obtained in recordings from the ipsilateral subiculum, suggested that the hippocampal impulses were relayed to layers VI-V of the entorhinal area by the subiculum. The delayed activation of layers IV-II was possibly mediated by intracortical connections. Double-shock experiments showed that impulses of hippocampal origin inhibited the response to dorsal psalterium volleys of entorhinal neurons giving origin to perforant path fibers. The data show that the hippocampal output activates the deep layers of the entorhinal area from which it is possibly relayed to numerous cortical and subcortical regions. Moreover, the inhibitory effects exerted on neurons originating perforant path fibers give evidence of a negative feedback control system operating in the hippocampal region.

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

The present study quantities 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 enkephalin in the perforant pathway, not in nerve fibers in the fimbria/fornix, which provide the other main source of hippocampal efferents. The enkephalins are likely to be intrinsicc to the hippocampus, in which neuronal cell bodies containing enkephalin-like immunoreactivity have been extensively reported.

Hippocampal kindling in the rat: intrastructural differences.

Kindling patterns were compared in different regions of the hippocampus of the rat. The duration, morphology, and frequency of the electrical responses were different after stimulation of the dorsal and the ventral hippocampus, but these parameters showed the same evolution as kindling progressed. Comparison of the threshold intensity and of the kindling rate revealed some differences not only between dorsal and ventral hippocampus, but also within the dorsal hippocampus: The central layers had higher thresholds and longer kindling periods than the outer layers and the fimbria hippocampi. We suggest that stimulation of hippocampal efferents is responsible for the greater ease of kindling in the outer layers than in the central regions of this structure. The degree of connection of the different parts of the hippocampus with the amygdala and the influence of the intrinsic inhibitory GABAergic circuitry are discussed.