2024/02/19 by Jack Lindsey, Jeffrey E. Markowitz, Winthrop F. Gillis +2 · 1 voice
Medicine · Neuroscience · #Neurological disorders and treatments #Neuroscience and Neuropharmacology Research #Neurotransmitter Receptor Influence on Behavior
paper · pdf · doi:10.1101/2024.02.14.580408
openalex publication_date 2024/02/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Spiny projection neurons (SPNs) in dorsal striatum are often proposed as a locus of reinforcement learning in the basal ganglia. Here, we identify and resolve a fundamental inconsistency between striatal reinforcement learning models and known SPN synaptic plasticity rules. Direct-pathway (dSPN) and indirect-pathway (iSPN) neurons, which promote and suppress actions, respectively, exhibit synaptic plasticity that reinforces activity associated with elevated or suppressed dopamine release. We show that iSPN plasticity prevents successful learning, as it reinforces activity patterns associated with negative outcomes. However, this pathological behavior is reversed if functionally opponent dSPNs and iSPNs, which promote and suppress the current behavior, are simultaneously activated by efferent input following action selection. This prediction is supported by striatal recordings and contrasts with prior models of SPN representations. In our model, learning and action selection signals can be multiplexed without interference, enabling learning algorithms beyond those of standard temporal difference models.