Mechanisms of the influence of dopamine on the functioning of basal ganglia and movement choice (a comparison of models)

Abstract

Previously, we proposed a unified model of the influence of dopamine on the functioning of the topically organized closed cortico-basal ganglia-thalamo-cortical loops that are involved in movement choice and the processing of sensory information [Biosystems. 2001. 59(1): 7–14; 2007. 89(1–3): 227–235]. In this model, the activity of cortical neurons that initiate movement depends on the type of triggering of striatonigral and striatopallidal cells, which express D1 and D2 receptors, respectively, and form “direct” and “indirect” projections via the basal ganglia. The signals that pass via the “direct” and “indirect” pathways have disinhibiting and inhibiting influences on the thalamic cells that project to the cortex. According to our modulation rules, dopamine promotes long-term potentiation of the efficacy of cortical inputs, which strongly activate striatonigral and weakly activate striatopallidal neurons, and long-term depression of inputs that weakly activate striatonigral and strongly activate striatopallidal neurons. Therefore, dopamine synergistically increases disinhibition and decreases inhibition of thalamic neurons, which excite initially strongly activated cortical neurons. Simultaneously, thalamic neurons, which excite initially weakly activated cortical neurons, became less disinhibited and more inhibited. As a result of an increase in the activity of certain groups of striatonigral and striatopallidal neurons, one movement is selected and competing movements are suppressed. According to some models that consider modulation of only strong corticostriatal inputs, a dopamine-dependent increase in the activity of striatonigral neurons promotes the performance of a movement and weakening of the activity of striatopallidal cells prohibits a movement or suppresses competing movements. Modern experimental data support our model. The use of Cre-dependent viral expression of a genetically encoded calcium probe allowed to record the activities of identified striatal neurons with D1 and D2 receptors in mice that press a lever in response to a sensory stimulus. It was shown that this movement is preceded by a considerable increase in the activities of both striatonigral and striatopallidal cells [Nature. 2013. 494(7436): 238–242].