Meeting Abstract

S1.2  Tuesday, Jan. 4  Brainstem neurons switch each other into pacemaker mode to drive movement by activating NMDARs LI, W.*; ROBERTS, A; SOFFE, S.R.; the University of St Andrews; the University of Bristol; the University of Bristol wl21@st-andrews.ac.uk

Rhythmic activity is central to brain function. In the vertebrate central nervous system, the neuronal circuits for breathing and locomotion involve inhibition and also neurons acting as pacemakers, but identifying the neurons responsible has proven difficult. By studying simple hatchling frog tadpoles, we have already identified a population of electrically coupled hindbrain neurons (dINs) which drive swimming. During rhythm generation dINs release glutamate to excite each other and activate NMDA receptors (NMDARs). The resulting depolarization enables a network mechanism for swimming rhythm generation which depends on reciprocal inhibition between antagonistic right and left sides. Surprisingly, a surgically isolated hemi-CNS without inhibition can still generate swimming-like rhythms. We have now discovered that activation of NMDARs transforms dINs, which normally fire singly to current injection, into pacemakers firing within the normal swimming frequency range (10-25 Hz). When dIN firing is blocked pharmacologically, this NMDAR activation produces 10 Hz membrane potential oscillations which persist when electrical coupling is blocked but not when the voltage-dependent gating of NMDARs by Mg2+ is removed. The NMDA-induced oscillations and pacemaker firing at swimming frequency are unique to the dIN population and do not occur in other spinal neurons. We conclude that NMDAR-mediated self-resetting switches critical neurons which drive swimming into pacemaker mode only during locomotion where it provides an additional, parallel mechanism for rhythm generation. This allows rhythm generation in a half CNS and raises the possibility that such concealed pacemaker properties may be present underlying rhythm generation in other vertebrate brain networks.