Dopaminergic modulation of the striatal microcircuit: receptor-specific configuration of cell assemblies

纹状体微回路的多巴胺能调节:细胞集合的受体特异性配置

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Abstract

Selection and inhibition of motor behaviors are related to the coordinated activity and compositional capabilities of striatal cell assemblies. Striatal network activity represents a main step in basal ganglia processing. The dopaminergic system differentially regulates distinct populations of striatal medium spiny neurons (MSNs) through the activation of D(1)- or D(2)-type receptors. Although postsynaptic and presynaptic actions of these receptors are clearly different in MSNs during cell-focused studies, their activation during network activity has shown inconsistent responses. Therefore, using electrophysiological techniques, functional multicell calcium imaging, and neuronal population analysis in rat corticostriatal slices, we describe the effect of selective dopaminergic receptor activation in the striatal network by observing cell assembly configurations. At the microcircuit level, during striatal network activity, the selective activation of either D(1)- or D(2)-type receptors is reflected as overall increases in neuronal synchronization. However, graph theory techniques applied to the transitions between network states revealed receptor-specific configurations of striatal cell assemblies: D(1) receptor activation generated closed trajectories with high recurrence and few alternate routes favoring the selection of specific sequences, whereas D(2) receptor activation created trajectories with low recurrence and more alternate pathways while promoting diverse transitions among neuronal pools. At the single-cell level, the activation of dopaminergic receptors enhanced the negative-slope conductance region (NSCR) in D(1)-type-responsive cells, whereas in neurons expressing D(2)-type receptors, the NSCR was decreased. Consequently, receptor-specific network dynamics most probably result from the interplay of postsynaptic and presynaptic dopaminergic actions.

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