Genetically tagging cholinergic diversity

Abstract

In this issue of Neuron, Li et al. (2022) identify and genetically target two sub-populations of cholinergic neurons in the basal forebrain. They show that these cholinergic subtypes have distinct projection patterns, electrophysiological phenotypes, and behavioral functions.

Figure 1.. Calbindin-D28K separates basal forebrain cholinergic neurons into two topographically, molecularly and functionally distinct sub-populations

(A) Combining triple-enzymatic-recombination-mutant (TERM) mice with recombinase-dependent viral injections allows for separate targeting of D28K⁺ and D28K⁻ neurons. (B) D28K⁺ and D28K⁻ neurons in the medial septum preferentially project to the ventral and dorsal hippocampus, respectively. (C) D28K⁺ neurons exhibited lower firing rate and higher firing threshold than D28K⁻ neurons. (D) A voltage-gated potassium channel (encoded by kcnh1) and a voltage-gated calcium channel (encoded by cacna1h) are selectively expressed in D28K⁺ and D28K⁻ neurons, respectively. This partly explains their distinct electrophysiological phenotypes. (E) Knockout of kcnh1 in D28K⁺ and cacna1h in D28K⁻ neurons has distinct behavioral effects.