Raphe Grafts in the Hippocampus, But Not in the Entorhinal Cortex, Reverse Hippocampal Hyperexcitability of Serotonin-Depleted Rats and Restore Their Responsiveness to Fenfluramine

Richter‐Levin, Gal; Segal, Menahem

doi:10.1159/000111660

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…Raphe grafts in the hippocampus reduced the behavioural impairment. When located in the hypothalamus such grafts had no effect on spatial learning, as was found with raphe grafts in the entorhinal cortex (Richter-Levin and Segal, 1992;Richter-Levin et a/., 1993). In addition, we now found that the 5,7-DHT lesions affected the forebrain serotonergic fibres but had a much smaller effect on the midbrain serotonergic innervation.…”

Section: Discussionsupporting

confidence: 68%

Differential Effects of Serotonin and Raphe Grafts in the Hippocampus and Hypothalamus: A Combined Behavioural and Anatomical Study in the Rat

Richter‐Levin¹,

Acsády

Freund

et al. 1994

Eur J of Neuroscience

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Combined with a partial cholinergic deficiency, serotonergic lesions induce severe spatial learning deficits. Serotonergic lesions, however, have additional effects, such as reduced body weight and disruption of thermoregulation, which may be the cause of the observed learning deficits. Restoration of the serotonergic innervation of the hippocampus by raphe grafts reduces these learning deficits. The effects of the grafts may result from a direct support of spatial learning but may also be an indirect result of preventing some of the other effects of serotonergic lesions. In the present study we used raphe grafts to examine the selectivity and specificity of the effects of serotonergic lesions in the rat, and used the behavioural effects as an indication of successful transplantation in order to examine the fine details of such grafts. Raphe grafts in the hippocampus did not prevent the effects of the lesions on body weight, thermoregulation and exploratory behaviour but did minimize the effects of the lesions on spatial learning. In contrast, raphe grafts in the hypothalamus reduced the effects of the lesions on thermoregulation but failed to support learning. The grafted fibres showed termination specificity with the interneurons, which is typical of the serotonergic innervation of the normal hippocampus. The results indicate that the serotonergic innervation of the hippocampus functions locally to support spatial learning. This role of serotonin is independent of its involvement in modulation of body weight, thermoregulation or exploratory behaviour. The results confirm that the modes of serotonergic action in the hippocampus include the selective innervation of specific interneuron subpopulations.

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Section: Discussionsupporting

confidence: 68%

Differential Effects of Serotonin and Raphe Grafts in the Hippocampus and Hypothalamus: A Combined Behavioural and Anatomical Study in the Rat

Richter‐Levin¹,

Acsády

Freund

et al. 1994

Eur J of Neuroscience

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“…The finding that mEPSCs are not affected, neither in frequency nor in amplitude, could be in line with the following scenario: 5-HT could induce a hyperpolarization of the presynaptic pyramidal cell, mediated by the opening of GIRK channels by 5-HT 1A receptor activation ( Andrade and Nicoll 1987 ; Segal et al 1989 ; Schmitz et al 1995 ). This would diminish the frequency of sEPSCs because of a decrease in the number of spontaneous spikes as has been shown in vivo ( Richter-Levin and Segal 1992 ). This possibility seems to be unlikely because application of a GIRK-channel blocker could not prevent the reduction of excitatory synaptic transmission onto O-LM interneurons by 5-HT.…”

Section: Discussionmentioning

confidence: 85%

Serotonin Attenuates Feedback Excitation onto O-LM Interneurons

et al. 2015

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The serotonergic system is a subcortical neuromodulatory center that controls cortical information processing in a state-dependent manner. In the hippocampus, serotonin (5-HT) is released by ascending serotonergic fibers from the midbrain raphe nuclei, thereby mediating numerous modulatory functions on various neuronal subtypes. Here, we focus on the neuromodulatory effects of 5-HT on GABAergic inhibitory oriens lacunosum-moleculare (O-LM) cells in the hippocampal area CA1 of the rat. These interneurons are thought to receive primarily local excitatory input and are, via their axonal projections to stratum lacunosum-moleculare, ideally suited to control entorhinal cortex input. We show that 5-HT reduces excitatory glutamatergic transmission onto O-LM interneurons. By means of paired recordings from synaptically connected CA1 pyramidal cells and O-LM interneurons we reveal that this synapse is modulated by 5-HT. Furthermore, we demonstrate that the reduction of glutamatergic transmission by serotonin is likely to be mediated via a decrease of calcium influx into presynaptic terminals of CA1 pyramidal cells. This modulation of excitatory synaptic transmission onto O-LM interneurons by 5-HT might be a mechanism to vary the activation of O-LM interneurons during ongoing network activity and serve as a brain state-dependent switch gating the efficiency of entorhinal cortex input to CA1 pyramidal neurons.

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“…These data suggest that both 5‐HT 1A and NMDA receptor activation may regulate neurogenesis throughout changes in activity of mature granule cells, via common or independent pathways. In the present study, transplanted foetal 5‐HT neurons may also affect neurogenesis via the same mechanism, because electrophysiological studies have demonstrated that raphe cells grafted into the hippocampus can prevent the 5‐HT‐depletion‐induced hyperexcitability of the dentate gyrus (Richter‐Levin & Segal 1992). Thus, although serotonergic denervation may have affected granule cell proliferation via changing overall electrical activity in the brain, the present transplantation study supports the view that 5‐HT may act locally on adult neurogenesis in the hippocampal formation.…”

Section: Discussionmentioning

confidence: 88%

“…1989, 1991). Furthermore, raphe grafts can reverse the 5‐HT‐depletion‐induced hyperexcitability of granule cells to perforant path stimulation (Richter‐Levin & Segal 1992) and ameliorate spatial memory impairments caused by combined lesions of 5‐HT and cholinergic neurons (Nilsson et al . 1990; Richter‐Levin et al .…”

Section: Introductionmentioning

confidence: 99%

Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons

Brezun

Daszuta

2000

Eur J of Neuroscience

204

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The long-term effects of hippocampal serotonergic denervation and reinnervation by foetal raphe tissue were examined in the dentate gyrus where neurons are continously born in the adult. Complete lesion of serotonin neurons following injections of 5, 7-dihydroxytryptamine in the dorsal and medial raphe nuclei produced long-term decreases in the number of newly generated granule cells identified with 5-Bromo-2'-deoxyuridine (BrdU) and the polysialylated form of neural cell adhesion molecule (PSA-NCAM) immunostaining, as observed in 2-month-survival rats. The raphe grafts, but not the control grafts of embryonic spinal tissue, reversed the postlesion-induced decreases in the density of BrdU- and PSA-NCAM-labelled cells detected in the granule layer. Inhibition of serotonin synthesis in animals with raphe grafts reversed back to lesion-induced changes in granule cell proliferation. Furthermore, extensive serotonergic reinnervation of the dentate gyrus in the area proximal to the raphe graft could be associated with supranormal density of BrdU-labelled cells. These results indicate that serotonin may be considered a positive regulatory factor of adult granule cell proliferation. Finally, the lack of effect of embryonic nonserotonergic tissue grafted to serotonin-deprived rats suggests that neurotrophic factors may not be involved in the effects of serotonin on adult neurogenesis.

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Raphe Grafts in the Hippocampus, But Not in the Entorhinal Cortex, Reverse Hippocampal Hyperexcitability of Serotonin-Depleted Rats and Restore Their Responsiveness to Fenfluramine

Cited by 8 publications

References 15 publications

Differential Effects of Serotonin and Raphe Grafts in the Hippocampus and Hypothalamus: A Combined Behavioural and Anatomical Study in the Rat

Differential Effects of Serotonin and Raphe Grafts in the Hippocampus and Hypothalamus: A Combined Behavioural and Anatomical Study in the Rat

Serotonin Attenuates Feedback Excitation onto O-LM Interneurons

Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons

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