Midbrain Modulation of Conditioned Learning

Abstract

The firing activity of dorso-medial-striatal-cholinergic interneurons (dmCINs) is a neural correlate of classical conditioning. dmCINs are tonically active and briefly pause in response to salient stimuli. This mediates the acquisition of the association between predictive cues and outcomes. Cortical and thalamic inputs represent the rather limited knowledge about the underlying circuitry contributing to this function. Here we aim to dissect the midbrain GABA and Glutamate to dmCIN pathways and evaluate how they influence conditioned behavior. We report that midbrain neurons, at the population level, discriminate auditory cues and encode the association of a predictive stimulus with a footshock. Furthermore, GABA and Glutamate cells form monosynaptic contacts onto dmCINs but also di-synaptic ones via the thalamic-parafasicular sub-nucleus. Finally, pathway-specific inhibition of each sub-circuit produces differential impairments of fear-conditioned learning suggesting that each component of such a complex network carries information pertinent to sub-domains of the behavioral strategy.