III-60. Neural dynamics following optogenetic disruption of motor preparation

The primary motor cortex (M1) plays a prominent role in the initiation and control of voluntary movements. Due to its direct link with behaviour, M1 is an ideal platform to study how brain state and behaviour are related to single neuron dynamics. We perform patch-clamp recordings and somatic current injections in the M1 of awake mice to characterise the intracellular activity and integrative properties of excitatory neurons in supercial (L2/3) and deep (L5B) layers during quiet wakefulness and movement. We find that during quiet wakefulness, L2/3 neurons display sparse spiking activity (0.5+0.7 Hz) while L5B cells display sustained firing (5.6+3.5 Hz) and that the membrane potential (Vm) in both cortical layers is characterized by slow fluctuations in the delta-band range (2-4 Hz). We identified two subpopulations of pyramidal cells in L5B -the main output layer of M1that either suppressed (L5Bsupp) or enhanced (L5Benh) their firing rates during movement. In L5Bsupp neurons, movement decreased slow Vm oscillations and variance with no change in mean Vm, resulting in divisive gain modulation and reduced spike rates. In L5Benh neurons, movement also reduced slow Vm oscillations but this effect was counterbalanced by a net depolarization and increased Vm fluctuations in the high frequency band (12-50 Hz), resulting in increased firing rates. Based on integrate-and-fire simulations, we estimate that during movement L5Benh neurons preferentially receive an increase in excitatory inputs (%) with more substantial correlations on a fine time-scale. Together, these changes have a linear multiplicative effect on the input-output gain of L5Benh neurons. Our data demonstrate a remarkable diversity among cortical layers, a strong modulation of integrative properties depending on brain state and suggest that the cortex exploits behavior-dependent modes of operation.