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Chang, C. Y.

Publications and source records attributed to Chang, C. Y..

3 recordsLinked to original sources

Dopamine transients delivered in learning contexts do not act as model-free prediction errors

Dopamine neurons fire transiently in response to unexpected rewards. These neural correlates are proposed to signal the reward prediction error described in model-free reinforcement learning algorithms. This error term represents the unpredicted or excess value of the rewarding event. In model-free reinforcement learning, this value is then stored as part of the learned value of any antecedent cues, contexts or events, making them intrinsically valuable, independent of the specific rewarding event that caused the prediction error. In support of equivalence between dopamine transients and this model-free error term, proponents cite causal optogenetic studies showing that artificially induced dopamine transients cause lasting changes in behavior. Yet none of these studies directly demonstrate the presence of cached value under conditions appropriate for associative learning. To address this gap in our knowledge, we conducted three studies where we optogenetically activated dopamine neurons while rats were learning associative relationships, both with and without reward. In each experiment, the antecedent cues failed to acquired value and instead entered into value-independent associative relationships with the other cues or rewards. These results show that dopamine transients, constrained within appropriate learning situations, support valueless associative learning.

neuroscience

Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66-independent targeting of NogoA

NogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction with its receptors, Nogo66/NgR. Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways. We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM. Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway. Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1-G93A. Thus, Pgk1 secreted from muscle is detrimental to motoneuron synapse growth and maintenance.

developmental biology

Causal evidence supporting the proposal that dopamine transients function as a temporal difference prediction error

Reward-evoked dopamine is well-established as a prediction error. However the central tenet of temporal difference accounts - that similar transients evoked by reward-predictive cues also function as errors - remains untested. To address this, we used two phenomena, second-order conditioning and blocking, in order to examine the role of dopamine in prediction error versus reward prediction. We show that optogenetically-shunting dopamine activity at the start of a reward-predicting cue prevents second-order conditioning without affecting blocking. These results support temporal difference accounts by providing causal evidence that cue-evoked dopamine transients function as prediction errors.

neuroscience