A Corticostriatal Path Targeting Striosomes Controls Decision-Making under Conflict

Abstract

SUMMARY A striking neurochemical form of compartmentalization has been found in the striatum of humans and other species, dividing it into striosomes and matrix. The function of this organization has been unclear, but the anatomical connections of striosomes indicate their relation to emotion-related brain regions including the medial prefrontal cortex. We capitalized on this fact by combining pathway-specific optogenetics and electrophysiology in behaving rats to search for selective functions of striosomes. We demonstrate that a medial prefronto-striosomal circuit is selectively active in and causally necessary for cost-benefit decision-making under approach-avoidance conflict conditions known to evoke anxiety in humans. We show that this circuit has unique dynamic properties likely reflecting striatal interneuron function. These findings demonstrate that cognitive and emotion-related functions are, like sensory-motor processing, subject to encoding within compartmentally organized representations in the forebrain, and suggest that striosome-targeting corticostriatal circuits can underlie neural processing of decisions fundamental for survival.

Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons

“…This possibility is of great interest, because striosomes are in a position to modulate and transmit signals to the SNc from limbic regions of the neocortex that are known to be dysregulated in mood disorders in humans (5,6). Despite much experimental work, however, the fundamental architecture of striosomal fiber arborizations within the substantia nigra (SN) and their relation to the recipient dopamine-containing neurons has remained unknown.…”

Analysis of complex neural circuits with nonlinear multidimensional hidden state models

“…2F whereas the DMS neuron was in an active state from gate opening to turn and the PFC neuron was active in relation to reward delivery. The decoded states of this triplet of neurons match the wellestablished relationship among the SNpc, DMS, and PFC in decision-making (24,26). The hidden states decoded by the NMHS model matched the behavioral states of rats far better than those decoded by the HMM (Fig.…”

“…2C). The activity of these three regions in decision-making tasks has been documented (24). SNpc neurons fire in anticipation of a reward (26).…”

“…2 A and B). We categorized putative two-and three-neuron microcircuits as bidirectional or unidirectional based on responses to the microstimulation (24). Recordings of the identified circuits were made as rats performed a decision-making task (Fig.…”

“…DMS neurons are active in the decision-making period. PFC neurons are activated after the turn and reach maximal activity when the rat consumes the reward (24). Recordings for each behavioral trial were divided into intervals based on behavioral events: the opening of the start gate, the turn, and the consumption of the reward.…”