Dopaminergic Modulation of the Striatal Microcircuit: Receptor-Specific Configuration of Cell Assemblies

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.

Activity Dynamics and Signal Representation in a Striatal Network Model with Distance-Dependent Connectivity

“…Analyses of such high-density sampling of striatal neurons showed that striatal activity is organized as spatially compact clusters of coactivated neurons (or NAs; Barbera et al, 2016; R. Costa, personal communication). Similar observations were made earlier in in vitro (Carrillo-Reid et al, 2011) and in task-related activity in behaving monkeys (Adler et al, 2013). In an unhealthy low-dopamine state (as in Parkinson’s disease), D2 type dopamine receptor expressing striatal projection neurons increase their firing rates (Mallet et al, 2006), and in general, striatal neuronal activity loses its diversity and ability to switch neuronal activity in a task-dependent fashion (Costa et al, 2006; Costa, 2011).…”

Duration differences of corticostriatal responses in striatal projection neurons depend on calcium activated potassium currents

“…This in turn regulates correlated firing among neuronal ensembles to produce network dynamics (Carrilo-Reid et al, 2008). Therefore, they may be a part of the explanation of the actions of modulatory transmitters at the striatal microcircuit (Carrillo-Reid et al, 2009a; Jáidar et al, 2010; Carrillo-Reid et al, 2011). …”

Direct Evaluation of L-DOPA Actions on Neuronal Activity of Parkinsonian TissueIn Vitro

“…All the procedures followed the National University of Mexico guidelines, the Guide for the Care and Use of Laboratory Animals (National Institutes of Health), in accordance with the EC Directive 86/609/EEC for animal experiments. The slice preparation and its analysis have been described before [3, 20, 22]. Briefly, corticostriatal slices (250  μ m in thickness) were obtained either from control or 6-hydroxydopamine (6-OHDA) treated rodents (mice or rats, postnatal day 23–29).…”