Pause and rebound: sensory control of cholinergic signaling in the striatum

Cholinergic interneurons have emerged as one of the key players controlling network functions in the striatum. Extracellularly recorded cholinergic interneurons acquire characteristic responses to sensory stimuli during reward-related learning, including a pause and subsequent rebound in spiking. However, the precise underlying cellular mechanisms have remained elusive. Here, we review recent advances in our understanding of the regulation of cholinergic interneuron activity. We discuss evidence of mechanisms that have been proposed to underlie sensory responses, including antagonistic actions by dopamine, recurrent inhibition via local interneurons, and an intrinsically generated membrane hyperpolarization in response to excitatory inputs. The review highlights outstanding questions and concludes with a model of the sensory responses and their downstream effects through dynamic acetylcholine receptor activation.