Abstract
It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans.
Highlights
DYT1 dystonia is a rare, dominantly inherited form of dystonia, caused almost exclusively by a specific deletion of three base pairs in the TOR1A gene (Ozelius et al, 1997)
The core assumptions of this theory are that (1) dopamine release in the striatum signals errors in the prediction of reward, with dopamine levels increasing following successful actions and decreasing when actions fail to achieve the expected outcome, (2) fluctuations in dopamine modulate downstream plasticity in recently active corticostriatal synapses such that synapses responsible for positive prediction errors are strengthened through long-term potentiation (LTP), and those that led to disappointment are weakened through long-term depression (LTD) (Reynolds et al, 2001), and (3) the efficacy of corticostriatal transmission affects voluntary action selection
We demonstrated that DYT1 dystonia patients and healthy controls have different profiles of risk sensitivity in a trial-and-error learning task
Summary
DYT1 dystonia is a rare, dominantly inherited form of dystonia, caused almost exclusively by a specific deletion of three base pairs in the TOR1A gene (Ozelius et al, 1997). Brain slices of transgenic rodents expressing the human mutant TOR1A gene show abnormally strong long-term potentiation (LTP; Martella et al, 2009) and weak, or even absent, long-term depression (LTD; Grundmann et al, 2012; Martella et al, 2009) in corticostriatal synapses, as compared to wildtype controls. The core assumptions of this theory are that (1) dopamine release in the striatum signals errors in the prediction of reward, with dopamine levels increasing following successful actions (to signal a positive prediction error) and decreasing when actions fail to achieve the expected outcome (a negative prediction error), (2) fluctuations in dopamine modulate downstream plasticity in recently active corticostriatal synapses such that synapses responsible for positive prediction errors are strengthened through long-term potentiation (LTP), and those that led to disappointment are weakened through long-term depression (LTD) (Reynolds et al, 2001), and (3) the efficacy of corticostriatal transmission affects voluntary action selection
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