Compartment-specific dendritic information processing in striatal cholinergic interneurons is reconfigured by peptide neuromodulation

Cholinergic interneurons are central hubs of the striatal neuronal network, controlling information processing in a behavioral-state-dependent manner. It remains unknown, however, how such state transitions influence the integrative properties of these neurons. To address this, we made simultaneous somato-dendritic recordings from identified rodent cholinergic interneurons, revealing that action potentials are initiated at dendritic sites because of a dendritic axonal origin. Functionally, this anatomical arrangement ensured that the action potential initiation threshold was lowest at axon-bearing dendritic sites, a privilege efficacy powerfully accentuated at the hyperpolarized membrane potentials achieved in cholinergic interneurons following salient behavioral stimuli. Experimental analysis revealed the voltage-dependent attenuation of the efficacy of non-axon-bearing dendritic excitatory input was mediated by the recruitment of dendritic potassium channels, a regulatory mechanism that, in turn, was controlled by the pharmacological activation of neurokinin receptors. Together, these results indicate that the neuropeptide microenvironment dynamically controls state- and compartment-dependent dendritic information processing in striatal cholinergic interneurons. [Display omitted] •The axon has a dendritic origin in the majority of striatal cholinergic interneurons•The impact of excitatory input to distinct dendritic domains is highly voltage dependent•Excitatory input to non-axon-bearing dendrites is suppressed by IA potassium channels•Substance P modulates IA channels to nullify dendritic domain specificity Striatal cholinergic interneurons are integral for adaptive behaviors. Williams et al. show that the operation of these neurons is context dependent. When in a state associated with salient behavioral stimuli, excitatory input has an asymmetric impact across dendritic domains. This inequality is nullified when neurons receive a modulatory signal from striatal output neurons.