The basal ganglia (BG) is a collection of nuclei located deep beneath the cerebral cortex that is involved in learning and selection of rewarded actions. Here, we analyzed BG mechanisms that enable these functions. We implemented a rate model of a BG-thalamo-cortical loop and simulated its performance in a standard action selection task. We have shown that potentiation of corticostriatal synapses enables learning of a rewarded option. However, these synapses became redundant later as direct connections between prefrontal and premotor cortices (PFC-PMC) were potentiated by Hebbian learning. After we switched the reward to the previously unrewarded option (reversal), the BG was again responsible for switching to the new option. Due to the potentiated direct cortical connections, the system was biased to the previously rewarded choice, and establishing the new choice required a greater number of trials. Guided by physiological research, we then modified our model to reproduce pathological states of mild Parkinson's and Huntington's diseases. We found that in the Parkinsonian state PMC activity levels become extremely variable, which is caused by oscillations arising in the BG-thalamo-cortical loop. The model reproduced severe impairment of learning and predicted that this is caused by these oscillations as well as a reduced reward prediction signal. In the Huntington state, the potentiation of the PFC-PMC connections produced better learning, but altered BG output disrupted expression of the rewarded choices. This resulted in random switching between rewarded and unrewarded choices resembling an exploratory phase that never ended. Along with other computational studies, our results further reconcile the apparent contradiction between the critical involvement of the BG in execution of previously learned actions and yet no impairment of these actions after BG output is ablated by lesions or deep brain stimulation. We predict that the cortico-BG-thalamo-cortical loop conforms to previously learned choice in healthy conditions, but impedes those choices in disease states.

11The basal ganglia (BG) is a collection of nuclei located deep beneath the cerebral cortex that is 12 involved in learning and selection of rewarded actions. Here, we analyzed BG mechanisms that 13 enable these functions. We implemented a rate model of a BG-thalamo-cortical loop and 14 simulated its performance in a standard action selection task. We have shown that potentiation of 15 corticostriatal synapses enables learning of a rewarded option. However, these synapses became 16 redundant later as direct connections between prefrontal and premotor cortices (PFC-PMC) were 17 potentiated by Hebbian learning. After we switched the reward to the previously unrewarded 18 option (reversal), the BG was again responsible for switching to the new option. Due to the 19 potentiated direct cortical connections, the system was biased to the previously rewarded choice, 20 and establishing the new choice required a greater number of trials. Guided by physiological 21 research, we then modified our model to reproduce pathological states of mild Parkinson's and 22Huntington's diseases. We found that in the Parkinsonian state PMC activity levels become (expected more than received), a pause in DA release leads to negative reinforcement and blocks 70 the action. As a mechanism for this control, DA modulates plasticity of synaptic projections from 71 the cortex to striatal medium spiny neurons (MSNs) (21,22). As a reflection of the bidirectional 72 DA modulation, there are two types of MSNs. Those that are responsible for promoting 73 movement are part of the BG direct pathway and express D1-type dopamine receptors (GO, D1-74 MSNs) and those that inhibit movement are part of the BG indirect pathway and express D2 75 dopamine receptors (NO-GO, D2-MSNs) (23-25). Indirect and direct BG pathways respectively 76 inhibit or disinhibit the thalamocortical relay neurons responsible for producing particular 77 movements (26-28). The coordination of activity within the two types of MSNs determines 78 action (29-31). Within the BG loops, synaptic plasticity of corticostriatal projections is a key 79 node in the learning of rewarded choices (9)(10)(11)22). 80The BG is suggested to remain involved in action selection after the action-reward 81 association is learned and control the transition from goal-directed to habitual choices (8,32). On 82 the other hand, clinical interventions for Parkinson disease (PD) do not cause impairments in 83 goal-directed or habitual movements (33)(34)(35). Specifically, GPi lesions and deep brain 84 stimulation, which disrupt the main output of the BG, are used to improve motor functions. This 85 observation gave rise to a hypothesis that the BG play a critical role in learning, but not in the 86 expression of already learned actions or choices (36,37). These choices are suggested to instead 87 be stored in synaptic connections within cortex. This hypothesis apparently contradicts the 88 suggested involvement of the BG in executing actions learned previously. Therefore, it is 89 essential to fill in this knowl...

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