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Serotonergic Signaling Controls Input-Specific Synaptic Plasticity at Striatal Circuits.

Anna Cavaccini1, Marta Gritti1, Andrea Giorgi2

  • 1Neuromodulation of Cortical and Subcortical Circuits Laboratory, Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.

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Summary

Serotonin (5-HT) signaling dampens a specific form of synaptic plasticity called spike-timing-dependent long-term depression (t-LTD) at thalamostriatal synapses. This occurs via the 5-HT4 receptor, impacting reward-based learning.

Keywords:
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Area of Science:

  • Neuroscience
  • Synaptic Plasticity
  • Neurotransmission

Background:

  • Monoaminergic systems, including dopamine and serotonin (5-HT), modulate the dorsal striatum (DS), essential for learning and action control.
  • While dopamine's role is well-studied, the synaptic impact of serotonin on DS function remains largely unknown.
  • Understanding serotonin's effects is critical for deciphering striatal-dependent processes.

Purpose of the Study:

  • To investigate the influence of serotonergic signaling on associative plasticity at glutamatergic synapses targeting direct pathway spiny projection neurons (dSPNs) in the DS.
  • To elucidate the specific mechanisms and receptor subtypes involved in serotonin's modulation of synaptic plasticity.

Main Methods:

  • Utilized chemogenetics and optogenetics to manipulate and assess serotonergic signaling.
  • Investigated spike-timing-dependent long-term depression (t-LTD) at thalamostriatal synapses.
  • Examined the role of the 5-HT4 receptor and its interaction with BK channels in regulating dendritic calcium (Ca2+) signals.

Main Results:

  • Impeding serotonergic signaling preferentially facilitated t-LTD at thalamostriatal synapses.
  • This t-LTD was dependent on the reduced activity of the 5-HT4 receptor subtype.
  • The 5-HT4 receptor was found to regulate dendritic Ca2+ signals by modulating BK channel activity, localizing to the dendritic shaft.

Conclusions:

  • Serotonergic signaling, particularly via the 5-HT4 receptor, plays a crucial role in gating t-LTD at thalamostriatal synapses.
  • This modulation influences plasticity in the dorsal striatum, impacting reward-based learning and action control.
  • Findings offer insights into how altered serotonin levels in various behavioral states or pathologies affect striatal functions.