Distinct electrophysiology and dopaminergic modulation of medium spiny neurons across divisions of the tail striatum and the dorsolateral striatum.

Abstract

The striatum is a brain region within the basal ganglia that plays a crucial role in generating behaviour and mediating perception. The tail striatum (TS) is a poorly understood striatal domain with predominantly sensory functions. Recent evidence supports that abnormal TS dopamine transmission in dopaminergic disease contributes to sensory symptoms by dysregulating TS medium spiny neurons (MSNs). Importantly, the ventral TS is segregated into medial, intermediate and lateral divisions in which TS-MSNs express D1 and D2 dopamine receptors unevenly, but the functional significance of this is unclear. We aimed to gain insight into the functional significance of this organisation and to investigate how TS-MSNs are modulated by dopamine. We used whole-cell patch clamping in rat (P45-55, both sexes) brain slices to conduct the first in-depth electrophysiological characterisation of TS-MSNs and compared them across divisions. The adjacent dorsolateral striatum (DLS) was included for comparison. We also investigated how bath-applied dopamine and selective dopamine agonists SKF38393 and quinpirole modulate MSNs in each region. We found that TS-MSNs are electrophysiologically distinct from DLS-MSNs, reflecting the established functional differences between these domains. TS-MSNs were more depolarised than DLS-MSNs at rest and had lower rheobase. We also identified functional heterogeneity across the TS divisions. The intermediate division had higher rheobase than the medial or lateral divisions. At rheobase, lateral division TS-MSNs showed higher firing frequencies than medial or intermediate division TS-MSNs. Finally, TS-MSNs showed weaker modulation by dopamine, SKF38393 and quinpirole than DLS-MSNs, which was also uneven across divisions. These data provide a novel electrophysiological characterisation of TS-MSNs, showing they are functionally distinct from DLS-MSNs and heterogeneous across divisions, which could have implications for dopaminergic diseases.