Molecular and Pathophysiological Studies of Striatal Neurons in Parkinson's Disease and Related Disorders

National Institute On Aging

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Abstract

Motor control depends on striatal direct and indirect pathways simultaneous, complementary control over downstream nuclei, and striatal projection neurons are hypothesized to convey implicit motivation through action vigor, or speed. A minority population of striosome or patch neurons clustered in compartments throughout the broader striatal matrix is proposed as a candidate for integrating external valence with emotional state and locomotor response. Striosome territories include both direct and indirect pathways similar to matrix, but striosomes greater connectivity to limbic structures and to dopamine neurons critical to locomotor function suggest striosomes may uniquely integrate innate valence, affect, and locomotion. Striosomes are increasingly implicated in value-based learning and decision making. Striosomes are shown to encode predictive cues signaling reward or punishment, especially early in training, and to be differentially quieted to facilitate discrimination between outcome values. Despite these patterns of engagement with learning, striosomes may be stronger champions of habitual than flexible performance. Their activity positively correlates with learned task-engagement and with perseverative errors, suggesting these cells may ultimately support a well learned choice to the detriment of new information. When the well learned task at hand is to choose between actions with different cost-benefit outcomes, striosome modulation gates cost aversion. Inhibiting these cells biases animals toward more cautious, risk avoidant choices, whereas disinhibiting them biases animals toward bolder reward seeking despite associated cost. Thus, existing studies implicate striosomes in evaluative roles critical to learning and to navigating learned contingencies, but do not indicate whether striosomes mediate unlearned assessment of innate valence. Here we sought to determine whether the striosome compartments increasingly recognized for serving reinforcement learning, learned choice selection, and task engagement have more immediate roles in shaping affect, innate situational valuation, or innate, valence-based motor performance. We found striosomal manipulation did not alter classic Light/Dark box anxiety measures, suggesting affect and valence perception were unchanged. However, we report evidence that striosomes modulate the innate, emotionally driven motor vigor with which untrained mice navigate high and low anxiety zones. This is the first evidence for a role of striosomal territories in modulating naturalistic motor behavior.