Serotonergic Signaling Controls Input-Specific Synaptic Plasticity at Striatal Circuits

Anna Cavaccini, Marta Gritti, Andrea Giorgi, Andrea Locarno, Nicolas Heck, Sara Migliarini, Alice Bertero, Maddalena Mereu, Giulia Margiani, Massimo Trusel, Tiziano Catelani, Roberto Marotta, Maria Antonietta De Luca, Jocelyne Caboche, Alessandro Gozzi, Massimo Pasqualetti, Raffaella Tonini

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Monoaminergic modulation of cortical and thalamic inputs to the dorsal striatum (DS) is crucial for reward-based learning and action control. While dopamine has been extensively investigated in this context, the synaptic effects of serotonin (5-HT) have been largely unexplored. Here, we investigated how serotonergic signaling affects associative plasticity at glutamatergic synapses on the striatal projection neurons of the direct pathway (dSPNs). Combining chemogenetic and optogenetic approaches reveals that impeding serotonergic signaling preferentially gates spike-timing-dependent long-term depression (t-LTD) at thalamostriatal synapses. This t-LTD requires dampened activity of the 5-HT4 receptor subtype, which we demonstrate controls dendritic Ca2+ signals by regulating BK channel activity, and which preferentially localizes at the dendritic shaft. The synaptic effects of 5-HT signaling at thalamostriatal inputs provide insights into how changes in serotonergic levels associated with behavioral states or pathology affect striatal-dependent processes. Cavaccini and Gritti et al. combine chemogenetic and optogenetic approaches to show that serotonergic signaling provides a control mechanism of synaptic plasticity at thalamic inputs to the striatum.

Original languageEnglish (US)
Pages (from-to)801-816.e7
JournalNeuron
Volume98
Issue number4
DOIs
StatePublished - May 16 2018
Externally publishedYes

Keywords

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ASJC Scopus subject areas

  • Neuroscience(all)

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