Abstract Body

The basal ganglia are a set of subcortical nuclei involved in motor learning and action control. The main input nucleus of basal ganglia is the striatum, whose activity is primarily controlled by cortical and thalamic inputs. In the striatum, neurons of the direct (dSPN)- and the indirect (iSPN) output pathways integrate excitatory, inhibitory as well as neuromodulatory information.

Previous studies focused on the regulatory role of dopamine on cortical and thalamic inputs in the dorsolateral part of the striatum, while the synaptic effects of serotonin (5-HT) are largely unexplored.

By combining chemogenetic and optogenetic approaches, we demonstrated that serotonergic signaling controls spike-timing-dependent long-term depression (t-LTD) at thalamostriatal synapses on dSPN. This t-LTD requires dampened activity of the 5-HT4 receptor subtype, which we demonstrate shapes 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 on dSPN provide insights into how changes in serotonergic levels associated with behavioural states or pathology might affect the output of the striatum within the basal ganglia loop.