Ventral Hippocampal Neurons Research Articles

Renewal of extinguished fear activates ventral hippocampal neurons projecting to the prelimbic and infralimbic cortices in rats

Anatomical disconnection of the ventral hippocampus (VH) and medial prefrontal cortex (mPFC) impairs the renewal of extinguished fear in rats. Here we examined whether subpopulations of neurons in the VH that project to the mPFC, including the prelimbic cortex (PL) and infralimbic cortex (IL), are selectively or differentially engaged by the renewal of fear to an extinguished auditory conditioned stimulus (CS). Rats were ipsilaterally injected with two distinct fluorescent retrograde tracers into the IL and PL and then underwent fear conditioning, extinction and retrieval in distinct contexts. Ventral hippocampal neurons were found to project to both IL and PL, and a small number of neurons projected to both regions. Fos expression was similarly elevated in each subpopulation of mPFC-projecting neuron in animals tested outside the extinction context relative to those tested in the extinction context or home controls. Interestingly, this pattern of results is not consistent with circuit models suggesting a differential role for VH projections to PL and IL in the bidirectional regulation of fear expression after extinction. Rather, these data suggest that projections from the VH to both PL and IL are uniquely involved in fear renewal, but not the suppression of fear after extinction. VH neurons may drive fear renewal by fostering fear expression by exciting PL while limiting fear suppression by inhibiting IL.

Morphometry of ventral hippocampal neurons of CA1-CA4 fields in domestic cattle

The aim of the study was a morphometric analysis of the ventral hippocampal neurons of the individual CA1-CA4 fields in domestic cattle (Bos Taurus; N = 6). The hippocampus in cattle is formed by a sizable arched invagination of the medial wall of the lateral ventricle of the brain. The brains were removed and analyzed conventionally with a light microscope. The samples were stained by Nissl’s method. The morphometric analysis of the neurons of the hippocampal CA1-CA4 fields included the following parameters: the area of nervous cells and the area of the cell nucleus in μm2; the nucleus-to-cell ratio in %; the average diameter and perimeter of the nervous cell in μm. The morphometric investigations indicate that the cells of the pyramidal layer in the CA1-CA4 fields of the hippocampus in adult domestic cattle differ in terms of their size, shape, and surface area, as well as the surface area of the cell nucleus. The size of cells in CA1 was the largest, fluctuating around 22 μm, whereas in CA4 it amounted to about 19 μm. Cells in CA1 and CA2 had the largest diameter of about 24 µm, whereas cells in the CA4 field had the smallest diameter of about 20 µm. The results obtained suggest a novel approach to studying the morphometric properties of the hippocampus in domestic cattle. Morphometric studies of the central nervous system (CNS) are regarded as a valuable source of data on the function of environmental and pharmacological factors and their effects on several structures of the CNS.

Fear renewal preferentially activates ventral hippocampal neurons projecting to both amygdala and prefrontal cortex in rats.

Anxiety, trauma and stress-related disorders are often characterized by a loss of context-appropriate emotional responding. The contextual retrieval of emotional memory involves hippocampal projections to the medial prefrontal cortex and amygdala; however the relative contribution of these projections is unclear. To address this question, we characterized retrieval-induced Fos expression in ventral hippocampal (VH) neurons projecting to the prelimbic cortex (PL) and basal amygdala (BA) after the extinction of conditioned fear in rats. After extinction, freezing behavior (an index of learned fear) to the auditory conditioned stimulus was suppressed in the extinction context, but was “renewed” in another context. Hippocampal neurons projecting to either PL or BA exhibited similar degrees of context-dependent Fos expression; there were more Fos-positive neurons in each area after the renewal, as opposed, to suppression of fear. Importantly, however, VH neurons projecting to both PL and BA were more likely to express Fos during fear renewal than neurons projecting to either PL or BA alone. These data suggest that although projections from the hippocampus to PL and BA are similarly involved in the contextual retrieval of emotional memories, VH neurons with collaterals to both areas may be particularly important for synchronizing prefrontal-amygdala circuits during fear renewal.

Maternal care differentially affects neuronal excitability and synaptic plasticity in the dorsal and ventral hippocampus.

Variations in early life maternal care modulate hippocampal development to program distinct emotional-cognitive phenotypes that persist into adulthood. Adult rat offspring that received low compared with high levels of maternal licking and grooming (low LG offspring) in early postnatal life show reduced long term potentiation (LTP) and impaired hippocampal-dependent memory, suggesting a 'detrimental' maternal effect on neural development. However, these studies focused uniquely on the dorsal hippocampus. Emerging evidence suggests a distinct role of the ventral hippocampus in mediating aggression, anxiety, and fear-memory formation, which are enhanced in low LG offspring. We report that variations in maternal care in the rat associate with opposing effects on hippocampal function in the dorsal and ventral hippocampus. Reduced pup licking associated with suppressed LTP formation in the dorsal hippocampus, but enhanced ventral hippocampal LTP. Ventral hippocampal neurons in low LG offspring fired action potentials at lower threshold voltages that were of larger amplitude and faster rise rate in comparison with those in high LG offspring. Furthermore, recordings of excitatory postsynaptic potential-to-spike coupling (E-S coupling) revealed an increase in excitability of ventral hippocampal CA1 neurons in low LG offspring. These effects do not associate with changes in miniature excitatory postsynaptic currents or paired-pulse facilitation, suggesting a specific effect of maternal care on intrinsic excitability. These findings suggest region-specific influences of maternal care in shaping neural development and synaptic plasticity.

Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies

BackgroundIn sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. In the human brain, the hierarchical pathways of this neurodegeneration have been well established in Alzheimer’s disease (AD) and other sporadic tauopathies such as argyrophilic grain disorder and progressive supranuclear palsy but the molecular and cellular mechanisms supporting this progression are yet not known. These pathways appear to be associated with the intercellular transmission of pathology, as recently suggested in Tau transgenic mice. However, these conclusions remain ill-defined due to a lack of toxicity data and difficulties associated with the use of mutant Tau.ResultsUsing a lentiviral-mediated rat model of hippocampal NFD, we demonstrated that wild-type human Tau protein is axonally transferred from ventral hippocampus neurons to connected secondary neurons even at distant brain areas such as olfactory and limbic systems indicating a trans-synaptic protein transfer. Using different immunological tools to follow phospho-Tau species, it was clear that Tau pathology generated using mutated Tau remains near the IS whereas it spreads much further using the wild-type one.ConclusionTaken together, these results support a novel mechanism for Tau protein transfer compared to previous reports based on transgenic models with mutant cDNA. It also demonstrates that mutant Tau proteins are not suitable for the development of experimental models helpful to validate therapeutic intervention interfering with Tau spreading.

Ventral Hippocampal Neurons Are Shaped by Experience to Represent Behaviorally Relevant Contexts

Memories can be recalled at different levels of resolution, from a detailed rendition of specific events within a single experience to a broad generalization across multiple related experiences. Here we provide evidence that neural representations reflecting the specificity or generality of memories are differentially represented along the dorsoventral axis of the CA3 area of the rat hippocampus. In dorsal CA3, neurons rapidly associate the identity of events with specific locations whereas, in more ventrally located CA3 regions, neurons gradually accumulate information across extended training to form representations that generalize across related events within a spatial context and distinguish events across contexts.

Dexamethasone induces different morphological changes in the dorsal and ventral hippocampus of rats

Dexamethasone (DEX), a synthetic glucocorticoid widely used in neurological illnesses because of its antiinflammatory properties, has many serious side effects, including severe psychiatric symptoms such as psychoses. The hippocampus is divided in the dorsal hippocampus (DH) and ventral hippocampus (VH) with each region having a subfield of CA1 and CA3 pyramidal layers. Great interest has recently emerged showing that the DH and VH are functionally different. In our work we determined whether, and what, changes occurred, after five days of DEX (0.2mg/kg) treatment, on the dendritic morphology of the CA1 and CA3 pyramidal neurons of the DH and VH of adult Sprague-Dawley rats. The dendritic morphology and characteristics were measured by using the Golgi-Cox procedure followed by a Sholl analysis. DEX decreased the number of dendritic spines of both apical and basolateral dendrites. Interestingly, this decrease was more pronounced in the VH. Only the VH neurons were affected by DEX with a decrease in their total dendritic length (TDL). An interesting point is that the VH neurons are longer that the DH neurons among the groups injected with saline only as the control. The length per branch order was only altered in the apical dendritic tree of the CA1 neurons. These data taken together show that the VH is more susceptible to DEX and its neurons are larger than the DH neurons. These results support previous observations related to differences between the DH and VH and suggest differences in the expression of the glucocorticoid receptors in connectivity and the space to elongate their dendritic arbor.

Dendritic morphology of neurons in prefrontal cortex and ventral hippocampus of rats with neonatal amygdala lesion

Neonatal basolateral amygdala (nBLA) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Recently, we reported that nBLA lesions result in significant decreases in the dendritic spine number of layer 3 prefrontal cortex (PFC) pyramidal cells and medium spiny neurons of the nucleus accumbens (NAcc), which all changes after puberty. At present, we aimed to evaluate the effect of this lesion in pyramidal neurons of CA1 of the ventral hippocampus (VH) and layer 5 of the PFC. In order to assess the effects of nBLA lesions on the dendritic morphology of the PFC and VH neurons, we carried out nBLA lesions in rats on postnatal day (PD) 7, and then we studied the dendritic morphology of these two limbic subregions at prepubertal (PD35) and postpubertal (PD60) ages. Dendritic characteristics were measured by Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of nBLA lesions on the prepulse inhibition (PPI) and acoustic startle responses. The nBLA lesion induced a significant increase in dendritic length of layer 5 pyramidal neurons of the PFC at both ages, with a decrease in the dendritic spines density after puberty. The spine density of CA1 VH pyramidal neurons showed significant decreases at both ages. PPI was decreased in adulthood in the animals with an nBLA lesion. These results show that an nBLA lesion alters the dendritic morphology at the level of the PFC and VH in distinct ways before puberty, suggesting a disconnection between these limbic structures at an early age, and increasing our understanding of the implications of the VH in early amygdala dysfunction in schizophrenia.

Ventral Hippocampal Neurons Project Axons Simultaneously to the Medial Prefrontal Cortex and Amygdala in the Rat

The ventral hippocampus (VH) may have an important role in spatial memory processes and emotional behaviors through connections with the medial prefrontal cortex (mPFC) and amygdala. Although the mPFC and amygdala receive afferent projections from the VH, it has not been determined whether the individual VH neurons project to both the mPFC and the amygdala. In this study, antidromic responses to the mPFC and amygdala stimulation were evoked in single VH neurons. In addition, VH neurons were retrogradely double-labeled with fluorescent tracers injected in the mPFC and amygdala. VH neurons projecting to both the mPFC and amygdala were predominantly located in the subiculum and CA1 and bifurcated near or at the soma. Our anatomical and electrophysiological evidence for the presence of VH neurons projecting to both the mPFC and amygdala provides a previously unrecognized pathway from the hippocampus that simultaneously activates the mPFC and amygdala.

Comparisons of dorsal and ventral hippocampus cornu ammonis region 1 pyramidal neuron activity during trace eye-blink conditioning in the rabbit

Previous studies demonstrating a critical role of the hippocampus during trace eye-blink conditioning have focused primarily upon the dorsal portion of the structure. However, evidence suggests that a functional differentiation exists along the septotemporal axis of the hippocampus. In the present study, the activity of 2588 single cornu ammonis region 1 pyramidal neurons of the dorsal hippocampus and ventral hippocampus were recorded during trace and pseudo-eye-blink conditioning of the rabbit. Learning-related increases in dorsal hippocampus neuron firing rates were observed immediately prior to behavioral criterion, and increased over the course of training. Activation of dorsal hippocampus neurons during trace conditioning was also greater than that of ventral hippocampus neurons, including during the trace interval, in well-trained animals. An unexpected difference in the patterns of learning-related activity between hemispheres was also observed. Neurons of the dorsal hippocampus ipsilateral and contralateral to the trained eye, exhibiting significant increases in firing rate [rate increasing neurons], demonstrated the greatest magnitude of activation early and late in training, respectively. Rate increasing neurons of the dorsal hippocampus also exhibited a greater diversity of response profiles, with 69% of dorsal hippocampus rate increasing neurons exhibiting significant increases in firing rate during the conditioned stimulus and/or trace intervals, compared with only 8% of ventral hippocampus rate increasing neurons (the remainder of which were significantly responsive during only the unconditioned stimulus and/or post-unconditioned stimulus intervals). Only modest learning-related activation of ventral hippocampus neurons was observed, reflected as an increase in conditioning stimulus-elicited rate increasing neuron response magnitudes over the course of training. No differences in firing rate between dorsal hippocampus and ventral hippocampus neurons during a 1-day pre-training habituation session were observed. Thus, dorsal hippocampus activation is more robust, suggesting a more substantial role for these neurons in the processing of temporal information during trace eye-blink conditioning.

Ca3 neuronal activities of dorsal and ventral hippocampus are differentially altered in rats after prolonged post-ischemic survival

The aim of the present study is to explore the potential hyper-excitability of hippocampal CA3 neurons in rats after prolonged post-ischemic survival. We conducted 15-min four-vessel-occlusion ischemic episodes in rats, allowed these animals to survive for approximately 8 months and then examined the basic morphological features and population synaptic activities of CA3 neurons. In fixed tissue sections obtained from dorsal hippocampi of post-ischemic rats, we observed a complete loss of the CA1 neurons together with a shrunken CA1 sector. Extracellular recordings in slices revealed that the overall synaptic activities of dorsal hippocampal CA3 neurons were decreased in post-ischemic rats compared with sham-operated controls. Both sham control and post-ischemic ventral hippocampal neurons were capable of exhibiting intermittent spontaneous field potentials in slices. These spontaneous field potentials spread from the CA3 to the CA1 area and their generation relied on the activity of glutamate alpha-amino-3-hydroxy-5-methyl-4 isoxazole proprionic acid (AMPA) receptors. The propensity for displaying these spontaneous field potentials appeared to be greater in post-ischemic slices than sham control slices. Our data suggest that the hyper-excitability of the post-ischemic hippocampus, if it occurs, may preferentially take place in the ventral CA3 circuitry.

Locomotor activity and accumbens Fos expression driven by ventral hippocampal stimulation require D 1 and D 2 receptors

Numerous studies have suggested that excitatory projections from the ventral hippocampus to the nucleus accumbens modulate locomotor activity in rats. Furthermore, the ability of ventral hippocampal neurons to alter locomotor activity may involve the dense dopaminergic innervation found in the nucleus accumbens. The purpose of this study was to: (i) more fully characterize the locomotor effects of acute alterations in ventral hippocampal activity; (ii) ascertain the influence of dopamine agonists and antagonists on locomotor changes produced by altered ventral hippocampal activity; and (iii) use immediate early gene induction to determine whether dopamine antagonists alter the response of nucleus accumbens neurons to ventral hippocampal stimulation. By comparing a variety of excitatory amino acid agonists, it was found that ventral hippocampal infusion of N-methyl- d-aspartate elevated locomotor activity in a subconvulsive manner, while other excitatory amino acid receptor agonists did not. Inactivation of the ventral hippocampus achieved by lidocaine infusion did not suppress ongoing locomotor activity, nor did it affect amphetamine-induced increases in locomotor activity. Increases in locomotor activity induced by ventral hippocampal N-methyl- d-aspartate infusion were blocked by systemic administration of haloperidol (a D 2 receptor antagonist), SCH-23390 (a D 1 receptor antagonist) or reserpine. Cellular expression of the protein product of the immediate early gene, c-fos, was dramatically increased in the nucleus accumbens shell after ventral hippocampal N-methyl- d-aspartate infusion, and haloperidol, SCH-23390 and reserpine attenuated this effect. These results suggest that the increases, but not decreases, in ventral hippocampal activity have a measurable effect on ongoing rates of locomotion, and that this effect requires both D 1 and D 2 receptors. Moreover, the studies of Fos expression suggest that dopamine receptor antagonists attenuate neuronal responses to ventral hippocampal stimulation within the nucleus accumbens, a brain region important in the generation and maintenance of locomotor activity.

Two actions of vasopressin on neurons in the rat ventral hippocampus: A microiontophoretic study

Vasopressin (VP), applied by brief iontophoretic pulses on ventral hippocampus neurons in vivo, excited approximately 30% of the neurons tested. Glutamate (Glu) and acetylcholine (ACh) excited nearly all neurons recorded. A selective antagonist of vasopressin V1 receptors suppressed the VP-induced excitation and, in addition, suppressed the excitations induced by Glu but not those by ACh. The specificity of the action in the brain of this VP antagonist must therefore be doubted. Two excitatory amino acid antagonists, D(−)-2-amino-5-phosphonovaleric acid (2APV) and glutamic acid diethyl ester (GDEE), suppressed the responses to Glu and also those to VP. ACh excitations, tested in the same neurons, were little affected by 2APV and GDEE. The remaining 70% of VH neurons were not excitable with VP. However, the responses of these neurons to Glu but not to Ach, increased markedly both while the peptide was released and for tens of minutes thereafter. The increase in Glu responses induced by VP could not be prevented by the VP or excitatory amino acid receptor antagonists applied before the peptide. The possibility that the excitation and the potentiation of Glu responses caused by VP oriinated from two different actions of the peptide is discussed.

Chapter 15 Brain vasopressin: from electrophysiological effects to neurophysiological function

This chapter discusses the electrophysiological effects and the neurophysiological function of brain vasopressin (VP). The two different actions of VP on lateral septum (LS) and ventral hippocampus (VH) neurons in vivo and in vitro are discussed. One of the actions, the excitation of LS and VH neurons, resembles the action of glutamate (GLU) and other excitatory amino acids (EAA). The VP-induced excitation involves EAA receptors and can be a pharmacological effect of the peptide. The other action of VP on LS and VH neurons is to temporarily increase the responses of neurons to exogenous and synaptically released EAAs. This VP action, observed in the majority of the LS and VH neurons in vivo, can last for many minutes following termination of peptide administration. A significant increase in EAA transmission on LS neurons in vitro is obtained with peptide. It is thus conceivable that the EAA transmission-enhancing action of VP is a physiological action of the peptide, related to the function of the brain VP system in the LS and hippocampus, and in other brain structures innervated by this system.