Distinct neuronal subpopulations of one brainstem nucleus

PAOLO CAPELLI; MARIA SOLEDAD ESPOSITO; CHIARA PIVETTA; SILVIA ARBER

Monte Verita

Conferencia; The Assembly and Function of Neuronal Circuits; 2015

Walking is one of the most basic motor behaviors, yet organization and function of descending pathways carrying this important locomotor output remain largely elusive. Circuits located in the brainstem play an essential role in the control and modulation of spinal circuitry. Recently, we uncovered the existence of a complex but precise connectivity matrix between specific sub-regions of the brainstem and spinal motor neurons (Esposito, Capelli and Arber 2014; Nature 508 : 351-6). We hypothesize that the command lines in the brainstem may be organized according to functional modules and linked to diversification of motor programs. Here we show that intermingled excitatory and inhibitory descending projection neurons within particular subdomains of the rostral medulla project to highly distinct targets in the spinal cord. This anatomical dichotomy is paralleled by distinct functions of these two neuronal subpopulations in movement control. Using genetic and viral intersectional targeting strategies to selectively express optogenetic manipulators, we perform extracellular recordings of light-identified neurons in vivo and detect neurons with movement-related neuronal activity patterns. Behavioral interference by temporally precise optogenetic manipulation demonstrates that the two identified and intermingled neuronal subpopulations control opposing motor behaviors in freely moving mice. Whereas activation of the glutamatergic subpopulation promotes locomotion and activates movement, the inhibitory counterpart induces reliable movement arrest. Together, our work demonstrates the existence of precisely organized yet spatially intermingled neuronal circuit elements in the brainstem involved in the control of brake and go mechanisms used by animals during natural behavior.