Neuron-Specific Cholinergic Modulation of a Forebrain Song Control Nucleus

Abstract

Cholinergic activation profoundly affects vertebrate forebrain networks, but pathway, cell type, and modality specificity remain poorly understood. Here we investigated cell-specific cholinergic modulation of neurons in the zebra finch forebrain song control nucleus HVC using in vitro whole cell recordings. The HVC contains projection neurons that exclusively project to either another song motor nucleus RA (robust nucleus of the arcopallium) (HVC-RAn) or the basal ganglia Area X (HVC-Xn) and these populations are synaptically coupled by a network of GABAergic interneurons. Among HVC-RAn, we observed two physiologically distinct classes that fire either phasically or tonically to injected current. Muscarine excited phasic HVC-RAn and most HVC-Xn. Effects were observed under conditions of blockade of fast synaptic transmission and were reversed by atropine. In contrast, unlike what is commonly observed in mammalian systems, HVC interneurons were inhibited by muscarine and these effects were reversed by atropine. Thus cholinergic modulation reconfigures the HVC network in a more complex fashion than that implied by monolithic "gating." The two projection pathways are decoupled through suppression of the inhibitory network that links them, whereas each is simultaneously predominantly excited. We speculate that fluctuating cholinergic tone in HVC could modulate the interaction of song motor commands with basal ganglia circuitry associated with song perception and modification. Furthermore, if the in vitro distinction between RA-projecting neurons that we observed is also present in vivo, then the song system motor pathway exhibits greater physiological diversity than has been commonly assumed.