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Joram Feldon - One of the best experts on this subject based on the ideXlab platform.

  • Small lesions of the dorsal or Ventral Hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval, and combining them attenuates the acquisition rate of spatial reference memory.
    Hippocampus, 2020
    Co-Authors: Jonas Hauser, Joram Feldon, Luis H. Llano López, Pascual A. Gargiulo, Benjamin K. Yee
    Abstract:

    The importance of the Hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and Ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the Ventral Hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal Hippocampus or Ventral Hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and Ventral Hippocampus in mice. Evidence that Ventral Hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with Ventral lesions alone or combined lesions. The small Ventral lesions also led to anxiolysis in the elevated plus maze and over-generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small Ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and Ventral poles of the Hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal Hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the Ventral Hippocampus. Although the impairments following Ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and Ventral Hippocampus in spatial learning. Candidate neural substrates may include dorsoVentral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond Hippocampus.

  • Activation of dopaminergic neurotransmission in the medial prefrontal cortex by N-methyl-d-aspartate stimulation of the Ventral Hippocampus in rats.
    Neuroscience, 2005
    Co-Authors: Daria Peleg-raibstein, Wei-ning Zhang, Joram Feldon, Marie A. Pezze, B. Ferger, C.a Murphy, Tobias Bast
    Abstract:

    Abstract Many behavioral functions—including sensorimotor, attentional, memory, and emotional processes—have been associated with hippocampal processes and with dopamine transmission in the medial prefrontal cortex (mPFC). This suggests a functional interaction between Hippocampus and prefrontal dopamine. The anatomical substrate for such an interaction is the intimate interconnection between the Ventral Hippocampus and the dopamine innervation of the mPFC. The present study yielded direct neurochemical evidence for an interaction between Ventral Hippocampus and prefrontal dopamine transmission in rats by demonstrating that subconvulsive stimulation of the Ventral Hippocampus with N-methyl- d -aspartate (NMDA; 0.5 μg/side) activates dopamine transmission in the mPFC. Postmortem measurements revealed that bilateral NMDA stimulation of the Ventral Hippocampus, resulting in locomotor hyperactivity, increased the homovanillic acid/dopamine ratio, an index of dopamine transmission, in the mPFC; indices of dopamine transmission in any of five additionally examined forebrain regions (amygdala, nucleus accumbens shell/core, lateral prefrontal cortex, caudate putamen) were unaltered. In vivo microdialysis measurements in freely moving rats corroborated the suggested activation of prefrontal dopamine transmission by demonstrating that unilateral NMDA stimulation of the Ventral Hippocampus increased extracellular dopamine in the ipsilateral mPFC. The suggested influence of the Ventral Hippocampus on prefrontal dopamine may be an important mechanism for hippocampo-prefrontal interactions in normal behavioral processes. Moreover, it indicates that aberrant hippocampal activity, as found in neuropsychiatric diseases, such as schizophrenia and mood disorders, may contribute to disruption of certain cognitive and emotional functions which are extremely sensitive to imbalanced prefrontal dopamine transmission.

  • dissociation of function between the dorsal and the Ventral Hippocampus in spatial learning abilities of the rat a within subject within task comparison of reference and working spatial memory
    European Journal of Neuroscience, 2004
    Co-Authors: Helen H J Pothuizen, Wei-ning Zhang, Ana L Jongenrelo, Joram Feldon
    Abstract:

    Lesions restricted to the dorsal, but not the Ventral, Hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the Ventral Hippocampus are involved differentially in spatial reference and spatial working memory using a four-baited/four-unbaited version of the eight-arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within-subjects within-task comparison between the two forms of memory functions. Rats with N-methyl-d-aspartic acid-induced excitotoxic lesions of the dorsal Hippocampus, Ventral Hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with Ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the Ventral Hippocampus, with the former being preferentially involved in spatial learning.

  • The Ventral Hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the Ventral Hippocampus.
    Behavioural Brain Research, 2001
    Co-Authors: Wei-ning Zhang, Tobias Bast, Joram Feldon
    Abstract:

    Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal Hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the Ventral Hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the Ventral Hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the Ventral Hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the Ventral Hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the Ventral Hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the Ventral Hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the Ventral Hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the Ventral Hippocampus. Given that NMDA stimulation of the Ventral Hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the Ventral Hippocampus might be due to the concurrent severe disruption of normal Ventral hippocampal activity. However, strong stimulation of the Ventral Hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the Ventral Hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the Ventral Hippocampus increased locomotor activity in the open field.

  • The Ventral Hippocampus and fear conditioning in rats
    Experimental Brain Research, 2001
    Co-Authors: Tobias Bast, Wei-ning Zhang, Joram Feldon
    Abstract:

    Studies on the involvement of the rat Hippocampus in classical fear conditioning have focused mainly on the dorsal Hippocampus and conditioning to a context. However, the Ventral Hippocampus has intimate connections with the amygdala and the nucleus accumbens, which are involved in classical fear conditioning to explicit and contextual cues. Consistently, a few recent lesion studies have indicated a role for the Ventral Hippocampus in classical fear conditioning to explicit and contextual cues. The present study examined whether neuronal activity within the Ventral Hippocampus is important for the formation of fear memory to explicit and contextual cues by classical fear conditioning. Tetrodotoxin (TTX; 10 ng/side), which completely blocks neuronal activity, or muscimol (1 µg/side), which increases GABAA receptor-mediated inhibition, were bilaterally infused into the Ventral Hippocampus of Wistar rats before the conditioning session of a classical fear-conditioning experiment. Conditioning to a tone and the context were assessed using freezing as a measure of conditioned fear. TTX blocked fear conditioning to both tone and context. Muscimol only blocked fear conditioning to the context. The data of the present study indicate that activity of neurons in the Ventral Hippocampus is necessary for the formation of fear memory to both explicit and contextual cues and that neurons in the Ventral Hippocampus that bear the GABAA receptor are important for the formation of fear conditioning to a context. In addition, both bilateral muscimol (0.5 µg/side and 1 µg/side) and TTX (5 ng/side and 10 ng/side) infusion into the Ventral Hippocampus dose-dependently decreased locomotor activity in an open-field experiment.

Gina L. Forster - One of the best experts on this subject based on the ideXlab platform.

  • Corticosterone in the Ventral Hippocampus differentially alters accumbal dopamine output in drug-naïve and amphetamine-withdrawn rats
    Neuropharmacology, 2019
    Co-Authors: Brenna Bray, Kaci A. Clement, Dana Bachmeier, Matthew A. Weber, Gina L. Forster
    Abstract:

    Abstract Dysregulation in glucocorticoid stress and accumbal dopamine reward systems can alter reward salience to increase motivational drive in control conditions while contributing to relapse during drug withdrawal. Amphetamine withdrawal is associated with dysphoria and stress hypersensitivity that may be mediated, in part, by enhanced stress-induced corticosterone observed in the Ventral Hippocampus. Electrical stimulation of the Ventral Hippocampus enhances accumbal shell dopamine release, establishing a functional connection between these two regions. However, the effects of Ventral hippocampal corticosterone on this system are unknown. To address this, a stress-relevant concentration of corticosterone (0.24ng/0.5 μL) or vehicle were infused into the Ventral Hippocampus of urethane-anesthetized adult male rats in control and amphetamine withdrawn conditions. Accumbal dopamine output was assessed with in vivo chronoamperometry. Corticosterone infused into the Ventral Hippocampus rapidly enhanced accumbal dopamine output in control conditions, but produced a biphasic reduction of accumbal dopamine output in amphetamine withdrawal. Selectively blocking glucocorticoid-, mineralocorticoid-, or cytosolic receptors prevented the effects of corticosterone. Overall, these results suggest that the ability of corticosterone to alter accumbal dopamine output requires cooperative activation of mineralocorticoid and glucocorticoid receptors in the cytosol, which is dysregulated during amphetamine withdrawal. These findings implicate Ventral hippocampal corticosterone in playing an important role in driving neural systems involved in positive stress coping mechanisms in healthy conditions, whereas dysregulation of this system may contribute to relapse during withdrawal.

  • Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the Ventral Hippocampus during amphetamine withdrawal
    The European journal of neuroscience, 2014
    Co-Authors: Jamie L. Scholl, Michael J. Watt, Gina L. Forster, James E. Hassell, Kenneth J. Renner
    Abstract:

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, which are factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, stress-induced increases in Ventral hippocampal serotonin (5-HT) levels have been linked to coping mechanisms. The goal of this study was to investigate the neurobiological changes induced by amphetamine that contribute to stress sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pretreated with amphetamine (2.5 mg/kg, intraperitoneal) and then subjected to 2 weeks of withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular 5-HT, stress-induced increases in 5-HT levels were abolished in the Ventral Hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the Ventral Hippocampus blocked the stress-induced increase in 5-HT levels in saline-pretreated rats, suggesting that glucocorticoid receptors mediate stress-induced increases in 5-HT levels in the Ventral Hippocampus. However, mifepristone had no effect on stress-induced increases in 5-HT levels in the central amygdala, indicating that stress increases 5-HT levels in this region independently of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in Ventral hippocampal 5-HT levels combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening stress responsiveness.

  • Serotonin in the Ventral Hippocampus modulates anxiety-like behavior during amphetamine withdrawal.
    Neuroscience, 2014
    Co-Authors: Ashley Cook, Jamie L. Scholl, Mackenzie Mears, Michael J. Watt, Kenneth J. Renner, Gina L. Forster
    Abstract:

    Abstract Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the Ventral Hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reducing 5-HT levels in the Ventral Hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the Ventral Hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-dihydroxytryptamine (5,7-DHT) into the Ventral Hippocampus, which produced a 83% decrease in Ventral Hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing Ventral Hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting that diminished Ventral Hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the Ventral Hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5-mg/kg, i.p.) or saline for 2 weeks, and at 2 weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5 μM) bilaterally into the Ventral Hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by Ventral Hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the Ventral Hippocampus are critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse.

  • Influence of chronic amphetamine treatment and acute withdrawal on serotonin synthesis and clearance mechanisms in the rat Ventral Hippocampus
    The European journal of neuroscience, 2012
    Co-Authors: Jeffrey L. Barr, Jamie L. Scholl, Michael J. Watt, Kenneth J. Renner, Rajeshwari R. Solanki, Christopher A. Lowry, Gina L. Forster
    Abstract:

    Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the Ventral Hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. This goal of this study was to understand the mechanisms by which reduced Ventral Hippocampus serotonergic neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis (assessed by accumulation of serotonin precursor as a measure of the capacity of in vivo tryptophan hydroxylase activity), expression of serotonergic transporters, and in vivo serotonergic clearance using in vivo microdialysis, were assessed in the Ventral Hippocampus in adult male Sprague Dawley rats at 24 hours withdrawal from chronic amphetamine. Overall, results showed that diminished extracellular serotonin at 24 hours withdrawal from chronic amphetamine was not accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan hydroxylase activity), nor serotonin transporter expression or function in the Ventral Hippocampus, but instead was associated with increased expression and function of organic cation transporters (low affinity, high capacity serotonin transporters). These findings suggest that 24 hours withdrawal from chronic amphetamine reduces the availability of extracellular serotonin in the Ventral Hippocampus by increasing organic cation transporter-mediated serotonin clearance, which may represent at future pharmacological target for reversing anxiety states during drug withdrawal.

  • Serotonergic neurotransmission in the Ventral Hippocampus is enhanced by corticosterone and altered by chronic amphetamine treatment
    Neuroscience, 2011
    Co-Authors: Jeffrey L. Barr, Gina L. Forster
    Abstract:

    The Ventral Hippocampus modulates anxiety-like behavior in rats, and serotonergic transmission within the Hippocampus facilitates adaptation to stress. Chronic amphetamine treatment results in anxiety-like behavior in rats and reduced monoamine concentrations in the Ventral Hippocampus. Since reduced hippocampal serotonergic transmission in response to stress is observed in rats that display high anxiety-like behavior, anxiety states in amphetamine-treated rats may be associated with reduced stress-related serotonergic transmission in the Hippocampus. Therefore, using in vivo microdialysis in anesthetized rats, we investigated the effect of corticosterone infused locally into the Ventral Hippocampus on serotonergic transmission, and the effect of chronic amphetamine pretreatment on corticosteroid receptor protein expression and the corticosterone-induced serotonergic response. Extracellular serotonin in the Ventral Hippocampus was increased by corticosterone in drug naive rats, and this corticosterone-induced serotonin augmentation was blocked by the glucocorticoid receptor antagonist mifepristone. Furthermore, chronic pretreatment with amphetamine abolished the serotonin response to physiologically relevant corticosterone levels and reduced glucocorticoid receptor protein expression. Together, our results suggest that chronic amphetamine exposure reduces serotonergic neurotransmission, in part via alterations to glucocorticoid receptor-facilitation of serotonin release in the rat Ventral Hippocampus. Reduced serotonergic activity in the Ventral Hippocampus may contribute to altered stress responses and adaptive coping following repeated drug exposure.

I J A Urban - One of the best experts on this subject based on the ideXlab platform.

  • long lasting enhancement of synaptic excitability of ca1 subiculum neurons of the rat Ventral Hippocampus by vasopressin and vasopressin 4 8
    Brain Research, 1995
    Co-Authors: A N Chepkova, P French, D De Wied, A Ontskul, Geert M J Ramakers, V G Skrebitski, W H Gispen, I J A Urban
    Abstract:

    Abstract Vasopressin (VP) is axonally distributed in many brain structures, including the Ventral Hippocampus. Picogram quantities of VP injected into the Hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4r,Cyt6]VP(4–9[ and [pGIu4,Cyt6,]VP(4–8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4–8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA 1 /subiculum of the Ventral Hippocampus. The EPSPs were evoked by stimulating the stratum radiatum of the CAI field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30–45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60–120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often. but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl- d -aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4–8[ on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the Ventral Hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the Ventral Hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

  • Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat Ventral Hippocampus by vasopressin and vasopressin(4-8).
    Brain research, 1995
    Co-Authors: A N Chepkova, P French, D De Wied, A Ontskul, Geert M J Ramakers, V G Skrebitski, W H Gispen, I J A Urban
    Abstract:

    Vasopressin (VP) is axonally distributed in many brain structures, including the Ventral Hippocampus. Picogram quantities of VP injected into the Hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4,Cyt6]VP(4-9) and [pGlu4,Cyt6]VP(4-8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4-8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA1/subiculum of the Ventral Hippocampus. The EPSPs were evoked by stimulating the striatum radiatum of the CA1 field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30-45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60-120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often, but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4-8) on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the Ventral Hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the Ventral Hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

  • Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat Ventral Hippocampus by vasopressin and vasopressin(4–8)
    Brain Research, 1995
    Co-Authors: A N Chepkova, P French, D De Wied, A Ontskul, Geert M J Ramakers, V G Skrebitski, W H Gispen, I J A Urban
    Abstract:

    Abstract Vasopressin (VP) is axonally distributed in many brain structures, including the Ventral Hippocampus. Picogram quantities of VP injected into the Hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4r,Cyt6]VP(4–9[ and [pGIu4,Cyt6,]VP(4–8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4–8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA 1 /subiculum of the Ventral Hippocampus. The EPSPs were evoked by stimulating the stratum radiatum of the CAI field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30–45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60–120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often. but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl- d -aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4–8[ on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the Ventral Hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the Ventral Hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

A N Chepkova - One of the best experts on this subject based on the ideXlab platform.

  • long lasting enhancement of synaptic excitability of ca1 subiculum neurons of the rat Ventral Hippocampus by vasopressin and vasopressin 4 8
    Brain Research, 1995
    Co-Authors: A N Chepkova, P French, D De Wied, A Ontskul, Geert M J Ramakers, V G Skrebitski, W H Gispen, I J A Urban
    Abstract:

    Abstract Vasopressin (VP) is axonally distributed in many brain structures, including the Ventral Hippocampus. Picogram quantities of VP injected into the Hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4r,Cyt6]VP(4–9[ and [pGIu4,Cyt6,]VP(4–8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4–8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA 1 /subiculum of the Ventral Hippocampus. The EPSPs were evoked by stimulating the stratum radiatum of the CAI field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30–45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60–120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often. but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl- d -aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4–8[ on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the Ventral Hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the Ventral Hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

  • Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat Ventral Hippocampus by vasopressin and vasopressin(4-8).
    Brain research, 1995
    Co-Authors: A N Chepkova, P French, D De Wied, A Ontskul, Geert M J Ramakers, V G Skrebitski, W H Gispen, I J A Urban
    Abstract:

    Vasopressin (VP) is axonally distributed in many brain structures, including the Ventral Hippocampus. Picogram quantities of VP injected into the Hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4,Cyt6]VP(4-9) and [pGlu4,Cyt6]VP(4-8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4-8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA1/subiculum of the Ventral Hippocampus. The EPSPs were evoked by stimulating the striatum radiatum of the CA1 field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30-45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60-120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often, but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4-8) on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the Ventral Hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the Ventral Hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

  • Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat Ventral Hippocampus by vasopressin and vasopressin(4–8)
    Brain Research, 1995
    Co-Authors: A N Chepkova, P French, D De Wied, A Ontskul, Geert M J Ramakers, V G Skrebitski, W H Gispen, I J A Urban
    Abstract:

    Abstract Vasopressin (VP) is axonally distributed in many brain structures, including the Ventral Hippocampus. Picogram quantities of VP injected into the Hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4r,Cyt6]VP(4–9[ and [pGIu4,Cyt6,]VP(4–8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4–8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA 1 /subiculum of the Ventral Hippocampus. The EPSPs were evoked by stimulating the stratum radiatum of the CAI field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30–45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60–120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often. but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl- d -aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4–8[ on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the Ventral Hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the Ventral Hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

Edward D. Levin - One of the best experts on this subject based on the ideXlab platform.

  • Nicotinic antagonist administration into the Ventral Hippocampus and spatial working memory in rats.
    Neuroscience, 1997
    Co-Authors: R Felix, Edward D. Levin
    Abstract:

    Abstract Nicotinic acetylcholine receptors are important for maintaining optimal memory performance. In order to more fully characterize the involvement of nicotinic systems in memory, the contributions of nicotinic acetylcholine receptor subtypes were investigated. This study targeted the α7 and α4β2 nicotinic receptors in the Ventral Hippocampus, an area known to be important for spatial working memory. Antagonists of α7 and α4β2 receptors were locally infused into the Ventral Hippocampus of rats and the effects on memory were examined with the radial-arm maze. The subtype-specific competitive antagonists infused into separate groups of rats were methyllycaconitine citrate (an α7 antagonist) and dihydro-β-erythroidine hydrobromide (an α4β2 antagonist). Their effects on radial-arm maze performance were contrasted with the non-specific competitive antagonist, d -tubocurarine chloride. Significant deficits in radial-arm maze choice accuracy performance were found at 78.7 μg/side for methyllycaconitine and at 106.9 μg/side for dihydro-β-erythroidine. Increased response latency was also seen at these doses. Tubocurarine induced seizures at doses previously reported to have no effect. Wet dog shakes were seen in most rats at 0.1 μg/side with tubocurarine, 26.3 μg/side with methyllycaconitine and 106.9 μg/side with dihydro-β-erythroidine. This study suggests that both α7 and α4β2 nicotinic acetylcholine receptor subtypes are involved in working memory formation and that the Hippocampus is a critical site for nicotinic cholinergic involvement in memory function, though the high doses of antagonists needed to produce the memory impairment may have had less than completely specific effects.

  • Nicotinic, muscarinic and dopaminergic actions in the Ventral Hippocampus and the nucleus accumbens : effects on spatial working memory in rats
    Brain research, 1996
    Co-Authors: Jeff S. Kim, Edward D. Levin
    Abstract:

    Acetylcholine (ACh) systems have been widely shown to be important for memory. In particular, ACh hippocampal neurons are critical for memory formation, though ACh innervation of other areas such as the nucleus accumbens may also be important. There has also been increasing interest in ACh and dopaminergic (DA) interactions with regard to short-term spatial memory. In a series of studies, we have found that ACh and DA agonists and antagonists given systemically interact to influence memory. The critical neural loci of these interactions are not currently known. In the present study, we used local infusion techniques to examine the role of ACh and DA transmitter systems in the nucleus accumbens and the Ventral Hippocampus on radial-arm maze (RAM) working memory performance. Into the nucleus accumbens of rats, we infused the nicotinic ACh agonist nicotine, the nicotinic ACh antagonist mecamylamine, the DA agonist apomorphine, or the DA antagonist haloperidol. Into the Ventral Hippocampus, we infused nicotine, mecamylamine, the muscarinic ACh agonist pilocarpine, or the muscarinic ACh antagonist, scopolamine. The nicotinic ACh and DA interaction was tested by a hippocampal infusion of mecamylamine alone or together with the DA D2 agonist quinpirole given via subcutaneous injection. The results confirmed that both nicotinic and muscarinic ACh receptors in the Ventral Hippocampus play a significant role in spatial working memory. Blockade of either nicotinic or muscarinic ACh receptors caused significant impairments in RAM choice accuracy. However, infusion of either nicotinic or muscarinic agonists failed to improve choice accuracy. The interaction of DA D2 systems in different with hippocampal nicotinic blockade than with general nicotinic blockade. Systemic administration of quinpirole potentiated the amnestic effect of mecamylamine infused into the Ventral Hippocampus, whereas it was previously found to reverse the amnestic effect of systemically administered mecamylamine. In contrast to the significant effects of mecamylamine in the Hippocampus, no effects were found after infusion into the nucleus accumbens. Nicotine also was not found to have a significant effect on memory after intra-accumbens infusion. Neither the DA agonist apomorphine nor the DA antagonist haloperidol had a significant effect on memory after infusion into the nucleus accumbens. This study provides support for the involvement of nicotinic and muscarinic receptors in the Ventral Hippocampus in memory function. Ventral hippocampal nicotinic systems have significant interactions with D2 systems, but these differ from their systemic interactions. In contrast, nicotinic ACh and DA systems in the nucleus accumbens were not found in the current study to be important for working memory performance in the RAM.