Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

Bombardi, Cristiano; Giovanni, Giuseppe Di

doi:10.1007/s00221-013-3512-6

Cited by 58 publications

(43 citation statements)

References 86 publications

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“…Our study is the first to demonstrate loss of facilitation of PP-evoked pSpike amplitude produced by systemic 8-OH-DPAt. PPF and depression of the pSpike can give useful information about feedforward and feedback inhibitory circuits in the hippocampus (Bliss et al 2007). If the first stimulus of a pair is able to evoke a pSpike, a GABA A -mediated feedback inhibition lasting 10-20 ms prevents the second stimulus from evoking a pSpike.…”

Section: Discussionmentioning

confidence: 99%

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

et al. 2013

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plasticity was studied. Rats injected with 8-OH-DPAt exhibited a significant reduction in MDA and epileptic discharges, a decrease in paired-pulse facilitation and an increase in long-term potentiation. this study suggests that 8-OH-DPAt or in general 5-Ht 1A/7 agonists might be useful for the treatment of tLE and also have some beneficial effects on the comorbid cognitive disorders seen in epileptic patients.

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Section: Discussionmentioning

confidence: 99%

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

et al. 2013

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“…In rat deep nuclei, immunoreactivity for the 5-HT 2A receptor is located in pyramidal and non-pyramidal neurons (Morilak et al, 1993; Cornea-Hébert et al, 1999; Xu and Pandey, 2000; McDonald and Mascagni, 2007; Jiang et al, 2008; Bombardi, 2011; Bombardi and Di Giovanni, 2013). In the rat, 100% of the pyramidal cells express the 5-HT 2A receptor (McDonald and Mascagni, 2007; Bombardi, 2011).…”

Section: Expression Of 5-ht2 Receptor Subtypes In the Amygdaloid Complexmentioning

confidence: 99%

Neuronal localization of the 5-HT2 receptor family in the amygdaloid complex

Bombardi

2014

Front. Pharmacol.

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The amygdaloid complex (or amygdala), a heterogeneous structure located in the medial portion of the temporal lobe, is composed of deep, superficial, and “remaining” nuclei. This structure is involved in the generation of emotional behavior, in the formation of emotional memories and in the modulation of the consolidation of explicit memories for emotionally arousing events. The serotoninergic fibers originating in the dorsal and medial raphe nuclei are critically involved in amygdalar functions. Serotonin (5-hydroxytryptamine, 5-HT) regulates amygdalar activity through the activation of the 5-HT2 receptor family, which includes three receptor subtypes: 5-HT2A, 5-HT2B, and 5-HT2C. The distribution and the functional activity of the 5-HT2 receptor family has been studied more extensively than that of the 5-HT2A receptor subtypes, especially in the deep nuclei. In these nuclei, the 5-HT2A receptor is expressed on both pyramidal and non-pyramidal neurons, and could play a critical role in the formation of emotional memories. However, the exact role of the 5-HT2A receptor subtypes, as well as that of the 5-HT2B and 5-HT2C receptor subtypes, in the modulation of the amygdalar microcircuits requires additional study. The present review reports data concerning the distribution and the functional roles of the 5-HT2 receptor family in the amygdala.

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“…The effect of haloperidol on gamma oscillations is different from its effect on inhibition, suggesting that the increased inhibition is likely not the cause of the increased gamma oscillations in PGC-1α −/− slices. It is possible that haloperidol’s effect on gamma oscillations are through serotonin receptors (Bombardi and Di Giovanni, 2013; Schulz et al, 2012), rather than dopamine receptors. It remains to be determined whether haloperidol also has differential effects on gamma oscillations in vivo in mice with transcriptional dysregulation.…”

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confidence: 99%

Transcriptional dysregulation causes altered modulation of inhibition by haloperidol

Brady

Bartley

et al. 2016

Neuropharmacology

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Many neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism involve interneuron transcriptional dysregulation. The transcriptional coactivator PGC-1α regulates gene expression in GABAergic interneurons, which are important for regulating hippocampal network activity. Genetic deletion of PGC-1α causes a decrease in parvalbumin expression, similar to what is observed in schizophrenia postmortem tissue. Our lab has previously shown that PGC-1α−/− mice have enhanced GABAergic inhibition onto CA1 pyramidal cells, which increases the inhibition/excitation (I/E) ratio, alters hippocampal circuit function, and impairs hippocampal dependent behavior. The typical antipsychotic haloperidol, a dopamine receptor antagonist with selectivity for D2-like receptors, has previously been shown to increase excitation in the CA1 region of hippocampus. We therefore tested whether haloperidol could normalize the I/E balance in CA1 of PGC-1α−/− mice, potentially improving circuit function and behavior. Surprisingly, we discovered instead that interneuron transcriptional dysregulation caused by loss of PGC-1α alters the effects of haloperidol on hippocampal synaptic transmission and circuit function. Acute administration of haloperidol causes disinhibition in CA1 and decreases the I/E ratio onto CA1 pyramidal cells in slices from PGC-1α+/+ mice, but not PGC-1α−/− mice. The spread of activity in CA1, assessed by voltage sensitive dye imaging, is increased by haloperidol in slices from PGC-1α+/+ mice; however haloperidol decreases the spread of activity in slices from PGC-1α−/− mice. Haloperidol increased the power of hippocampal gamma oscillation in slices from PGC-1α+/+ mice but reduced the power of gamma oscillations in slices from PGC-1α−/− mice. Nest construction, an innate hippocampal-dependent behavior, is inhibited by haloperidol in PGC-1α+/+ mice, but not in PGC-1α−/− mice, which already have impaired nest building. The effects of haloperidol are mimicked and occluded by a D2 receptor antagonist in slices from PGC-1α+/+ mice, and the effects of blocking D2 receptors are lost in slices from PGC-1α−/− mice, although there is no change in D2 receptor transcript levels. Together, our results show that hippocampal inhibitory synaptic transmission, CA1 circuit function, and hippocampal dependent behavior are modulated by the antipsychotic haloperidol, and that these effects of haloperidol are lost in PGC-1α−/− mice. These results have implications for the treatment of individuals with conditions involving PGC-1α deficiency.

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Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

Abstract: suggest that 5-HT 2A receptor may be a potential therapeutic target for those disorders related to hippocampal and amygdala dysfunction.

Cited by 58 publications

References 86 publications

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

Neuronal localization of the 5-HT2 receptor family in the amygdaloid complex

Transcriptional dysregulation causes altered modulation of inhibition by haloperidol

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