Ventral CA1 Region Research Articles

Timp1 Deletion Induces Anxiety-like Behavior in Mice.

The hippocampus is essential for learning and memory, but it also plays an important role in regulating emotional behavior, as hippocampal excitability and plasticity affect anxiety and fear. Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a known protein inhibitor of extracellular matrix (ECM), and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli. However, the involvement of Timp1 in fear learning, anxiety, and hippocampal synaptic function remains to be established. Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning. Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region, but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway. Taken together, our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors, but that Timp1 is not crucial for fear learning.

Optogenetic stimulation of mouse Hoxb8 microglia in specific regions of the brain induces anxiety, grooming, or both

Previously, we have shown that either disruption of the Hoxb8 gene or ablation of a microglial subpopulation, Hoxb8 microglia, results in mice exhibiting both chronic anxiety and OCSD-like behavior, compulsive pathological hair pulling (trichotillomania), to the point of showing lesions at the sites of overgrooming. Herein we show, that optogenetic stimulation of Hoxb8 microglia in specific regions of the brain induces elevated anxiety, grooming or both. Optogenetic stimulation of Hoxb8 microglia within the dorsomedial striatum (DMS) or the medial prefrontal cortex (mPFC) induces grooming, whereas stimulation of Hoxb8 microglia in the basolateral amygdala (BLA) or central amygdala (CeA) produces elevated anxiety. Optogenetic stimulation of Hoxb8 microglia in the ventral CA1 region of the hippocampus (vCA1) induces both behaviors as well as freezing. In vitro we directly demonstrate that optogenetic stimulation of Hoxb8 microglia in specific regions of the brain activate neighboring neural activity through the induction of the c-fos-immediate early response. These experiments connect outputs from optogenetically stimulated Hoxb8 microglia, within specific regions of the brain, to the activation of neurons and neural circuits that in turn enable induction of these behaviors. These experiments suggest that Hoxb8 microglia are likely to be among, or the main, first responders to signals that evoke these behaviors. The same regions of the brain (DMS, mPFC, BLA, CeA and vCA1) have previously been defined at the neuronal level, by optogenetics, to control anxiety in mice. Intriguingly, the optogenetic experiments in microglia suggest that the two populations of microglia, canonical non-Hoxb8 and Hoxb8 microglia, function in opposition rather than in parallel to each other, providing a biological reason for the presence of two microglial subpopulations in mice.

Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous seizures and behavioral comorbidities. Reduced hippocampal theta oscillations and hyperexcitability that contribute to cognitive deficits and spontaneous seizures are present beyond the sclerotic hippocampus in TLE. However, the mechanisms underlying compromised network oscillations and hyperexcitability observed in circuits remote from the sclerotic hippocampus are largely unknown. Cholecystokinin (CCK)-expressing basket cells (CCKBCs) critically participate in hippocampal theta rhythmogenesis, and regulate neuronal excitability. Thus, we examined whether CCKBCs were vulnerable in nonsclerotic regions of the ventral hippocampus remote from dorsal sclerotic hippocampus using the intrahippocampal kainate (IHK) mouse model of TLE, targeting unilateral dorsal hippocampus. We found a decrease in the number of CCK+ interneurons in ipsilateral ventral CA1 regions from epileptic mice compared to those from sham controls. We also found that the number of boutons from CCK+ interneurons was reduced in the stratum pyramidale, but not in other CA1 layers, of ipsilateral hippocampus in epileptic mice, suggesting that CCKBCs are vulnerable. Electrical recordings showed that synaptic connectivity and strength from surviving CCKBCs to CA1 pyramidal cells (PCs) were similar between epileptic mice and sham controls. In agreement with reduced CCKBC number in TLE, electrical recordings revealed a significant reduction in amplitude and frequency of IPSCs in CA1 PCs evoked by carbachol (commonly used to excite CCK+ interneurons) in ventral CA1 regions from epileptic mice versus sham controls. These findings suggest that loss of CCKBCs beyond the hippocampal lesion may contribute to hyperexcitability and compromised network oscillations in TLE.

A ventral CA1 to nucleus accumbens core engram circuit mediates conditioned place preference for cocaine.

The importance of neuronal ensembles, termed engram cells, in storing and retrieving memory is increasingly being appreciated, but less is known about how these engram cells operate within neural circuits. Here we tagged engram cells in the ventral CA1 region of the hippocampus (vCA1) and the core of the nucleus accumbens (AcbC) during cocaine conditioned place preference (CPP) training and show that the vCA1 engram projects preferentially to the AcbC and that the engram circuit from the vCA1 to the AcbC mediates memory recall. Direct activation of the AcbC engram while suppressing the vCA1 engram is sufficient for cocaine CPP. The AcbC engram primarily consists of D1 medium spiny neurons, but not D2 medium spiny neurons. The preferential synaptic strengthening of the vCA1→AcbC engram circuit evoked by cocaine conditioning mediates the retrieval of cocaine CPP memory. Our data suggest that the vCA1 engram stores specific contextual information, while the AcbC D1 engram and its downstream network store both cocaine reward and associated contextual information, providing a potential mechanism by which cocaine CPP memory is stored.

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocampus in the long-lasting structural and behavioral effects of SPS. Two weeks after SPS, stressed rats displayed increased anxiety-like behavior and decreased preference for objects in novel locations regardless of the presence or absence of new neurons. Chronic stress produced by daily restraint for 2 or 6 hr produced similar behavioral effects that were also independent of ongoing neurogenesis. At a longer recovery time point, 1 month after SPS, rats with intact neurogenesis had normalized, showing control levels of anxiety-like behavior. However, GFAP-TK rats, which lacked new neurons, continued to show elevated anxiety-like behavior and enhanced serum corticosterone response to anxiogenic experience. Volume loss in ventral CA1 region of the hippocampus paralleled increases in anxiety-like behavior, occurring in all rats exposed to SPS at the early time point and only rats lacking adult neurogenesis at the later time point. In chronic stress experiments, volume loss occurred broadly throughout the dentate gyrus and CA1 after 6-hr daily stress but was not apparent in any hippocampal subregion after 2-hr daily stress. No effect of SPS was seen on cell proliferation in the dentate gyrus, but the survival of young neurons born a week after stress was decreased. Together, these data suggest that new neurons are important for recovery of normal behavior and hippocampal structure following a strong acute stress and point to the ventral CA1 region as a potential key mediator of stress-induced anxiety-like behavior.

Centrifugal Inputs to the Main Olfactory Bulb Revealed Through Whole Brain Circuit-Mapping.

Neuronal activity in sensory regions can be modulated by attention, behavioral state, motor output, learning, and memory. This is often done through direct feedback or centrifugal projections originating from higher processing areas. Though, functionally important, the identity and organization of these feedback connections remain poorly characterized. Using a retrograde monosynaptic g-deleted rabies virus and whole-brain reconstructions, we identified the organization of feedback projecting neurons to the main olfactory bulb of the mouse. In addition to previously described projections from regions such as the Anterior Olfactory Nucleus (AON) and the piriform cortex, we characterized direct projections from pyramidal cells in the ventral CA1 region of hippocampus and the entorhinal cortex to the granule cell layer (GCL) of the main olfactory bulb (MOB). These data suggest that areas involved in stress, anxiety, learning and memory are all tethered to olfactory coding, two synapses away from where chemical compounds are first detected. Consequently, we hypothesize that understanding olfactory perception, even at the earliest stages, may require studying memory and behavior in addition to studying the physiochemical features of odors.

Chronic Intermittent Ethanol Exposure Selectively Increases Synaptic Excitability in the Ventral Domain of the Rat Hippocampus

Many studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety- and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. To that end, we examined the effects of the chronic intermittent ethanol vapor exposure (CIE) model of AUD on dHC and vHC synaptic excitability. Adult male Long–Evans rats were exposed to CIE or AIR for 10 days (12 h/day; targeting blood ethanol levels of 175–225 mg%) and recordings were made 24 h into withdrawal. As expected, this protocol increased anxiety-like behaviors on the elevated plus-maze and successive alleys test. Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, were dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal.

A role for CA3 in social recognition memory

Social recognition memory is crucial for survival across species, underlying the need to correctly identify conspecifics, mates and potential enemies. In humans the hippocampus is engaged in social and episodic memory, however the circuit mechanisms of social memory in rodent models has only recently come under scrutiny. Work in mice has established that the dorsal CA2 and ventral CA1 regions play critical roles, however a more comprehensive comparative analyses of the circuits and mechanisms required has not been reported. Here we employ conditional genetics to examine the differential contributions of the hippocampal subfields to social memory. We find that the deletion of NMDA receptor subunit 1 gene (NR1), which abolishes NMDA receptor synaptic plasticity, in CA3 pyramidal cells led to deficits in social memory; however, mice lacking the same gene in DG granule cells performed indistinguishable from controls. Further, we use conditional pharmacogenetic inhibition to demonstrate that activity in ventral, but not dorsal, CA3 is necessary for the encoding of a social memory. These findings demonstrated CA3 pyramidal cell plasticity and transmission contribute to the encoding of social stimuli and help further identify the distinct circuits underlying the role of the hippocampus in social memory.

Distinct Effect of Stress on 11β-Hydroxysteroid Dehydrogenase Type 1 and Corticosteroid Receptors in Dorsal and Ventral Hippocampus

Multiple lines of evidence suggest the participation of the hippocampus in the feedback inhibition of the hypothalamus-pituitary-adrenal axis during stress response. This inhibition is mediated by glucocorticoid feedback due to the sensitivity of the hippocampus to these hormones. The sensitivity is determined by the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that regulates the conversion of glucocorticoids from inactive to active form. The goal of our study was to assess the effect of stress on the expression of 11HSD1, GR and MR in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulated 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats. In contrast, GR expression following stress was decreased in the dorsal but not ventral CA1 hippocampus of all three strains. MR expression was not changed in either the dorsal or ventral CA1 region. These results indicate that (1) depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas (2) independent of strain, stress inhibits GR in the dorsal hippocampus, which is predominantly involved in cognitive functions.

Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity

Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions.

Identification of a Role for the Ventral Hippocampus in Neuropeptide S-Elicited Anxiolysis

Neuropeptide S (NPS) increasingly emerges as a potential novel treatment option for anxiety diseases like panic and posttraumatic stress disorder. However, the neural underpinnings of its anxiolytic action are still not clearly understood. Recently, we reported that neurons of the ventral hippocampus (VH) take up intranasally administered fluorophore-conjugated NPS and, moreover, that application of NPS to mouse brain slices affects neurotransmission and plasticity at hippocampal CA3-CA1 synapses. Although these previous findings define the VH as a novel NPS target structure, they leave open whether this brain region is directly involved in NPS-mediated anxiolysis and how NPS impacts on neuronal activity propagation in the VH. Here, we fill this knowledge gap by demonstrating, first, that microinjections of NPS into the ventral CA1 region are sufficient to reduce anxiety-like behavior of C57BL/6N mice and, second, that NPS, via the NPS receptor, rapidly weakens evoked neuronal activity flow from the dentate gyrus to area CA1 in vitro. Additionally, we show that intranasally applied NPS alters neurotransmission and plasticity at CA3-CA1 synapses in the same way as NPS administered to hippocampal slices. Thus, our study provides, for the first time, strong experimental evidence for a direct involvement of the VH in NPS-induced anxiolysis and furthermore presents a novel mechanism of NPS action.

MDMA Induces EPSP–Spike Potentiation in Rat Ventral Hippocampus In Vitro Via Serotonin and Noradrenaline Release and Coactivation of 5-HT4 and β1 Receptors

It is well documented that N-methyl-3,4-methylenedioxyamphetamine (MDMA, ecstasy) releases brain serotonin (5-HT; 5-hydroxytryptamine), noradrenaline (NE; norepinephrine), and dopamine, but the consequent effect on brain functioning remains elusive. In this study, we characterized the effects of MDMA on electrically evoked responses in the ventral CA1 region of a rat hippocampal slice preparation. Superfusion with MDMA (10 microM, 30 min) increased the population spike amplitude (PSA) by 48.9+/-31.2% and decreased population spike latency (PSL) by 103+/-139 mus (both: mean+/-SD, n=123; p<0.0001, Wilcoxon test), without affecting field excitatory postsynaptic potential (fEPSP). This effect persisted for at least 1 h after MDMA washout; we have called this EPSP-spike potentiation (ESP) by MDMA, ESP MDMA. Antagonism of GABAergic transmission did not prevent ESP MDMA, suggesting that an increase in excitability of pyramidal cells underlies this MDMA action. Block of serotonin transporter (SERT) with citalopram or 5-HT depletion with (+/-)-p-chlorophenylalanine pretreatment partially inhibited the ESP MDMA. Block of both SERT and NE transporter prevented ESP MDMA, indicating its dependence on release of both 5-HT and NE. ESP MDMA is produced by simultaneous activation of 5-HT4 and beta1 receptors, with a predominant role of 5-HT4 receptors. Block of both 5-HT4 and beta1 receptors revealed an inhibitory component of the MDMA action mediated by 5-HT1A receptor. The concentration range of MDMA which produced ESP MDMA (1-30 microM) corresponds to that commonly reached in human plasma following the ingestion of psychoactive MDMA doses, suggesting that release of both 5-HT and NE, and consequent ESP MDMA may underlie some of the psychoactive effects of MDMA in humans.

Autonomic brainstem nuclei are linked to the hippocampus

Vagal nerve stimulation has been reported to enhance memory in both rats and humans, and to be an effective treatment for epilepsy in some patients, but the underlying neuroanatomical substrate(s) responsible for these effects remains unknown. Since there is no direct anatomical projection from the nucleus tractus solitarius, the main vagal relay site of the brain, to the hippocampus, we tested whether a multisynaptic pathway exists. Pseudorabies virus, a pig herpesvirus that can be used as a retrograde transneuronal tracer, was injected into the ventral CA1 hippocampus of rats, and after 4 days, pseudorabies virus infected neurons were identified in the general visceral portion of the nucleus tractus solitarius, with the majority being localized in the A2 noradrenergic cell group. Other autonomic brainstem nuclei, including the parabrachial nucleus, locus coeruleus, A1 and A5 noradrenergic cell groups, and C1 adrenergic cell group, were labeled. In order to identify some of the potential relay sites of the nucleus tractus solitarius→hippocampal pathway, immunotoxin lesions of the ventral CA1 region were made that selectively destroyed either the noradrenergic or cholinergic fibers. After 2 weeks' recovery, pseudorabies virus was injected in this same CA1 area, and 4 days later, the transneuronal labeling in the nucleus tractus solitarius was reduced by approximately 65%. These findings suggest that the noradrenergic neurons of the locus coeruleus and cholinergic neurons of the medial septum/diagonal band are likely to be relay sites for this pathway. Other potential linkages are discussed. In summary, this is the first anatomical report to show that the general visceral region of nucleus tractus solitarius is linked via multisynaptic relays to the hippocampus.

Patterns of colocalization of neuronal nitric oxide synthase and somatostatin-like immunoreactivity in the mouse hippocampus: quantitative analysis with optical disector

In some brain regions, previous studies reported the frequent coexistence between neuronal nitric oxide synthase (nNOS) and somatostatin (SOM). In the hippocampus, nNOS and SOM were mainly expressed in GABAergic nonprincipal neurons. Here we estimated the immunocytochemical colocalization of nNOS and SOM in the mouse hippocampus using the optical disector. Both in the Ammon's horn and dentate gyrus, we encountered only a few nNOS-immunoreactive (IR)/SOM-like immunoreactive (LIR) neurons. They were mainly located in the stratum oriens of the Ammon's horn and in the dentate hilus. The nNOS-IR/SOM-LIR neurons usually showed characteristic large somata with thick dendrites, whereas the majority of nNOS-IR/SOM-negative neurons showed small somata with thin dendrites. Quantitative data revealed that the double-labeled cells represented only 4% and 7% of nNOS-IR neurons and SOM-LIR neurons, respectively, in the whole area of the hippocampus. We also found the laminar and dorsoventral differences in the degree of colocalization between nNOS and SOM. The percentages of nNOS-IR neurons containing SOM-like immunoreactivity were relatively high in the stratum oriens of the ventral CA1 region (24%), stratum lucidum of the dorsal CA3 region (29%) and dorsal dentate hilus (32%), but they were quite low in the other layers. On the other hand, the percentages of SOM-LIR neurons containing nNOS immunoreactivity were somewhat high in the stratum lucidum of the dorsal CA3 region (19%) and dorsal dentate hilus (28%), whereas they were very low in the other layers. Immunofluorescent triple labeling of axon terminals for nNOS, SOM and glutamic acid decarboxylase indicated that some nNOS-IR/SOM-LIR neurons might be dendritic inhibitory cells. The present results show the infrequent colocalization of nNOS and SOM in the mouse hippocampus, and also suggest that the double-labeled cells may be a particular subpopulation of hippocampal GABAergic nonprincipal neurons.

Differences in paired-pulse facilitation and long-term potentiation between dorsal and ventral CA1 regions in anesthetized rats.

To clarify hippocampal regional differences in synaptic plasticity, paired-pulse facilitation (PPF, a form of short-term plasticity), long-term potentiation (LTP, a form of long-term plasticity), and their interactions were studied in the dorsal and ventral hippocampal CA1 regions of anesthetized rats. Baseline PPF and post-LTP PPF experiments were conducted at interstimulus intervals (ISIs) of 20-320 ms. A general protocol (100 Hz, 1 s) and a stronger protocol (250-Hz pulse series) were applied for LTP induction. PPF were observed in both regions; however, the degree was lower and the range of ISIs was narrower in the ventral region compared with the dorsal region. The degree of ventral LTP was lower than that of the dorsal LTP. The interaction between PPF and LTP was observed in both regions (PPF change correlated inversely with degree of baseline PPF). However, this was also different in each region. Dorsal PPF increased or decreased; in contrast, ventral PPF of short ISIs after LTP only decreased. These regional differences in short-term and long-term synaptic plasticity may explain a consequence of different afferent inputs and information processing.

Plasticity at hippocampal to prefrontal cortex synapses: dual roles in working memory and consolidation.

The involvement of the hippocampus and the prefrontal cortex in cognitive processes and particularly in learning and memory has been known for a long time. However, the specific role of the projection which connects these two structures has remained elusive. The existence of a direct monosynaptic pathway from the ventral CA1 region of the hippocampus and subiculum to specific areas of the prefrontal cortex provides a useful model for conceptualizing the functional operations of hippocampal-prefrontal cortex communication in learning and memory. It is known now that hippocampal to prefrontal cortex synapses are modifiable synapses and can express different forms of plasticity, including long-term potentiation, long-term depression, and depotentiation. Here we review these findings and focus on recent studies that start to relate synaptic plasticity in the hippocampo-prefrontal cortex pathway to two specific aspects of learning and memory, i.e., the consolidation of information and working memory. The available evidence suggests that functional interactions between the hippocampus and prefrontal cortex in cognition and memory are more complex than previously anticipated, with the possibility for bidirectional regulation of synaptic strength as a function of the specific demands of tasks.

Laminar distribution of non-principal neurons in the rat hippocampus, with special reference to their compositional difference among layers

In the present study we examined the laminar distributions of four types of chemically defined subpopulations of non-principal neurons, that is, those immunoreactive for parvalbumin (PV), calretinin (CR), nitric oxide synthase (NOS) and somatostatin (SS), in the rat hippocampus, by estimating their approximate numerical densities (NDs) and percentages in specific layers according to the `disector' principle. CR-immunoreactive (CR-IR) neurons and NOS-IR neurons were scattered throughout layers, but among layers in each subdivision their NDs were largest in the principal cell layers, where 30–45% of CR-IR and NOS-IR somata in each subdivision were located. In addition, CR-IR and NOS-IR somata were also concentrated at the border between the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) in the CA1 region, where the NDs of these neurons were far larger than those in the SR/SLM as a whole and close to those in the stratum pyramidale (SP) (CR-IR somata at the ventral level and NOS-IR somata at the dorsal level) or larger (NOS-IR neurons at the ventral level). The NDs of CR-IR somata were dorsoventrally different in all layers of the CA3 region, the SR/SLM in the CA1 region and the hilus and the granule cell layer (GCL) of the dentate gyrus (DG), whereas the NDs of NOS-IR somata were dorsoventrally different in all layers of the CA3 region and the SP in the CA1 region. In contrast, approx. 90% of somatostatin-like immunoreactive (SS-LIR) neurons were located in the stratum oriens/alveus (SO/SA) in the CA1 region and in the hilus of the DG, where they were the most predominant cell type among the four types of non-principal cells. In contrast, in the CA3 region, SS-LIR somata were scattered in various layers. The majority (50–70%) of PV-IR neurons were located in the principal cell layers, whereas one-fourth to one-third of them were located in the SO/SA and hilus. The NDs in the SP of the CA1 and CA3 regions showed a significant dorsoventral difference. Although PV-IR somata were most numerous among the four non-principal cell groups in the SP of the dorsal CA1 region, they were not necessarily predominant in the principal layers in other regions, that is, in the ventral CA1 region, CA3 region and DG, where the NDs of CR-IR and/or NOS-IR somata were nearly equal to or larger than that of PV-IR somata. The present study not only reveals the laminar distribution patterns of four types of non-principal neurons in each subdivision quantitatively, but also illustrates the prominent differences in the compositions of four types of non-principal cells in each layer of each subdivision.

Hippocampal pathway to the amygdala and stress ulcer development

The objective of the first study was to localize the reported aggravation of stress ulcers found after large bilateral hippocampal lesions in rats. Lesions in the ventral hippocampus produced a similar increase in the severity of gastric erosions after cold-restraint, as was seen after large bilateral lesions. Dorsal hippocampal damage produced no differential effects. In the second experiment, high-frequency electrical stimulation of the ventral CA1 region of the hippocampus, a procedure known to induce long-term potentiation, increased the evoked potentials in the lateral central nucleus of the amygdala, and in adjacent parts of the lateral and basolateral nuclei. The increase in the efficacy of synaptic transmission in this pathway attenuated stress ulcer development. It was concluded that the ventral hippocampus is part of a coping system, and a strengthening of synaptic connections with the central amygdala increases the coping ability of rats under stress conditions.