KChIP4a is a biophysical amplifier of inhibition in atypical dopamine neurons and controls learning from negative prediction errors

Dopamine neurons that project to different brain areas have distinct cellular properties that are thought to support their specialized roles in behavior. Uncovering the genetic and molecular underpinnings of this functional diversity is critical for understanding how the dopamine system shapes learning and other behaviors in health and disease. We discovered that KChIP4a, a splice variant of a Kv4 potassium channel modulatory subunit, amplifies inhibition in a population of atypical dopamine neurons by changing the kinetics of Kv4 potassium channels. Moreover, removing KChIP4a from dopamine neurons selectively accelerated learning from reward omission, without affecting other behavioral variables. Our findings reveal a novel cell type-specific, alternative splicing-dependent, biophysical mechanism for fine-tuning distinct components of learning.