Serotonergic facilitation of synaptic activity in the developing rat prefrontal cortex

Béïque, Jean Claude; Chapin-Penick, Esther M.; Mladenovic, Ljiljana; Andrade, Rodrigo

doi:10.1113/jphysiol.2003.051284

Cited by 58 publications

(23 citation statements)

References 38 publications

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“…Consistent with previous reports, this increase in synaptic activity was blocked by the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/ kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3- dione (30 M; n ϭ 3; data not shown) and by tetrodotoxin (1 M; n Ͼ 10 cells; data not shown). In prefrontal cortical slices, administration of tetrodotoxin reduces the frequency of synaptic events indicating that a subset of neurons is spontaneously active (12). Together, these results recapitulate previous findings showing that activation of 5-HT 2A Rs in PFC induces an increase in glutamate-mediated sEPSCs recorded from layer V pyramidal neurons.…”

Section: Resultssupporting

confidence: 81%

“…6). These findings, in conjunction with previous reports using similar, although not identical, conditions and approaches (9,11,12) indicate that neither an increase in the probability of release nor an increase in the number or function of synaptic ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors is likely to contribute significantly to the effect of ␣m-5-HT on sEPSCs.…”

Section: Resultssupporting

confidence: 78%

“…Consistent with a previous report (25), paired recordings from layer V pyramidal neurons of acute slices showed that ␣m-5-HT induced a small inward current that fully recovered on agonist removal in control cells, while inducing an irreversible inward current in neighboring cells loaded with GTP␥S (Fig. 4A Lower; n ϭ 13 pairs).…”

Section: Gtp␥s Selectively Renders Irreversible the 5-ht2ar-induced Isupporting

confidence: 78%

“…Specifically, 5-HT 2A R activation did not appear to excite pyramidal neurons (4,9,11,25) but involved an increase in the release of glutamate by afferent presynaptic terminals (9,11,12,14). As such, the retrograde messenger hypothesis did seem to offer the only possible explanation for the phenomenon.…”

Section: Discussionmentioning

confidence: 97%

“…To that effect, a number of studies have addressed the electrophysiological effects signaled by 5-HT 2A Rs in this region. There is general concordance that the most robust cellular effect observed in pyramidal cell of the PFC on stimulation of 5-HT 2A Rs involves an increase in both the frequency and amplitude of glutamatergic spontaneous excitatory postsynaptic potentials/spontaneous excitatory postsynaptic currents (sEPSCs) (9)(10)(11)(12)(13)(14). This observation thus points to 5-HT 2A Rs as powerful modulators of the excitability of PFC networks and reconciles evidence implicating both glutamatergic and serotonergic systems in the actions of hallucinogens (15).…”

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confidence: 97%

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Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

Béïque¹,

Imad

Mladenovic³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Classic hallucinogens such as lysergic acid diethylamide are thought to elicit their psychotropic actions via serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT 2AR). One likely site for these effects is the prefrontal cortex (PFC). Previous studies have shown that activation of 5-HT2ARs in this region results in a robust increase in spontaneous glutamatergic synaptic activity, and these results have led to the widely held idea that hallucinogens elicit their effect by modulating synaptic transmission within the PFC. Here, we combine cellular and molecular biological approaches, including single-cell 5-HT 2ARs inactivation and 5-HT2AR rescue over a 5-HT 2AR knockout genetic background, to distinguish between competing hypotheses accounting for these effects. The results from these experiments do not support the idea that 5-HT 2ARs elicit the release of an excitatory retrograde messenger nor that they activate thalamocortical afferents, the two dominant hypotheses. Rather, they suggest that 5-HT 2ARs facilitate intrinsic networks within the PFC. Consistent with this idea, we locate a discrete subpopulation of pyramidal cells that is strongly excited by 5-HT 2AR activation.gene gun ͉ in vitro electrophysiology ͉ organotypic slices ͉ serotonin ͉ hallucinogen T he idea that classic hallucinogens such as lysergic acid diethylamide and psylocibin act by interfering with serotonergic neurotransmission can be traced to the middle of the 20th century (1). It was, however, not until the 1980s that serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT 2A R) were identified as the molecular target for these agents (refs. 2, 3; reviewed in refs. 4, 5). Subsequent brain imaging studies in human subjects have extended these findings to identify the prefrontal cortex (PFC), which is highly enriched in these receptors, as a key brain region in mediating the effects of hallucinogens (6, 7). These findings have led to the now widely accepted view that activation of 5-HT 2A R in the prefrontal is a key biological step leading to the psychological effects of hallucinogens (5, 8).Our understanding of the mechanisms by which 5-HT 2A R activation elicits the sensory and behavioral manifestation of hallucinogens would be enriched by a precise understanding of how these receptors modulate cellular and network excitability in the PFC. To that effect, a number of studies have addressed the electrophysiological effects signaled by 5-HT 2A Rs in this region. There is general concordance that the most robust cellular effect observed in pyramidal cell of the PFC on stimulation of 5-HT 2A Rs involves an increase in both the frequency and amplitude of glutamatergic spontaneous excitatory postsynaptic potentials/spontaneous excitatory postsynaptic currents (sEPSCs) (9)(10)(11)(12)(13)(14). This observation thus points to 5-HT 2A Rs as powerful modulators of the excitability of PFC networks and reconciles evidence implicating both glutamatergic and serotonergic systems in the actions of hallucinogens (15).Although multiple ...

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Section: Resultssupporting

confidence: 81%

Section: Resultssupporting

confidence: 78%

Section: Gtp␥s Selectively Renders Irreversible the 5-ht2ar-induced Isupporting

confidence: 78%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 97%

See 3 more Smart Citations

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

Béïque¹,

Imad

Mladenovic³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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204

118

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Developmental Effects of Selective Breeding for an Infant Trait

Brunelli

Zimmerberg

Hofer

2010

Handbook of Developmental Science, Behavior, and Genetics

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Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptors

Parga

Rodríguez‐Pallares

Muñoz

et al. 2006

Developmental Neurobiology

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Inductive signals mediating the differentiation of neural precursors into serotonergic (5-HT) or dopaminergic neurons have not been clarified. We have recently shown that in cell aggregates obtained from rat mesencephalic precursors, reduction of serotonin levels induces a marked increase in generation of dopaminergic neurons. In the present study we treated rat neurospheres with antagonists of the main subtypes of 5-HT receptors, 5-HT transport inhibitors, or 5-HT receptor agonists, and studied the effects on generation of dopaminergic neurons. Cultures treated with Methiothepin (5-HT 1,2,5,6,7 receptor antagonist), the 5-HT 4 receptor antagonist GR113808, or the 5-HT 7 receptor antagonist SB 269970 showed a significant increase in generation of dopaminergic cells. Treatment with the 5-HT 1B/1D antagonist GR 127935, the 5-HT 2 antagonist Ritanserin, the 5-HT transporter inhibitor Fluoxetine, the dopamine and norepinephrine transport inhibitor GBR 12935, or with both inhibitors together, or 5-HT 4 or 5-HT 7 receptor agonists induced significant decreases in generation of dopaminergic cells. Cultures treated with WAY100635 (5-HT 1A receptor antagonist), the 5-HT 3 receptor antagonist Ondasetron, or the 5-HT 6 receptor antagonist SB 258585 did not show any significant changes. Therefore, 5-HT 4 and 5-HT 7 receptors are involved in the observed serotonininduced decrease in generation of dopaminergic neurons from proliferating neurospheres of mesencephalic precursors. 5-HT 4 and 5-HT 7 receptors were found in astrocytes and serotonergic cells using double immunolabeling and laser confocal microscopy, and the glial receptors appeared to play a major role. '

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Serotonergic facilitation of synaptic activity in the developing rat prefrontal cortex

Cited by 58 publications

References 38 publications

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

Developmental Effects of Selective Breeding for an Infant Trait

Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptors

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