Low-Dimensional and Monotonic Preparatory Activity in Mouse Anterior Lateral Motor Cortex

Abstract

Neurons in multiple brain regions fire trains of action potentials anticipating specific movements, but this "preparatory activity" has not been systematically compared across behavioral tasks. We compared preparatory activity in auditory and tactile delayed-response tasks in male mice. Skilled, directional licking was the motor output. The anterior lateral motor cortex (ALM) is necessary for motor planning in both tasks. Multiple features of ALM preparatory activity during the delay epoch were similar across tasks. First, most neurons showed direction-selective activity and spatially intermingled neurons were selective for either movement direction. Second, many cells showed mixed coding of sensory stimulus and licking direction, with a bias toward licking direction. Third, delay activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar direction selectivity showed high spike-count correlations. Our study forms the foundation to analyze the neural circuit mechanisms underlying preparatory activity in a genetically tractable model organism. Short-term memories link events separated in time. Neurons in the frontal cortex fire trains of action potentials anticipating specific movements, often seconds before the movement. This "preparatory activity" has been observed in multiple brain regions, but has rarely been compared systematically across behavioral tasks in the same brain region. To identify common features of preparatory activity, we developed and compared preparatory activity in auditory and tactile delayed-response tasks in mice. The same cortical area is necessary for both tasks. Multiple features of preparatory activity, measured with high-density silicon probes, were similar across tasks. We find that preparatory activity is low-dimensional and monotonic. Our study forms a foundation for analyzing the circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

A comparison of neuronal population dynamics measured with calcium imaging and electrophysiology

“…What could be the cause of these differences? Spike rates in individual ALM neurons often increase or decrease during a trial in ramp-like patterns[ 25 , 34 , 45 ]. Right-preferring selectivity was more often associated with neurons ramping up on right trials, whereas left-preferring selectivity included many neurons with firing rates ramping down in the non-preferred ('right') trial ( Fig 2J ).…”

Flexible motor sequence generation during stereotyped escape responses

“…Actions may be generated by an inherently noisy system: synapses are unreliable ( Allen and Stevens, 1994 ), neurons generate variable spike trains ( Mainen and Sejnowski, 1995 ), and neural circuits may operate near the edge of chaos ( van Vreeswijk and Sompolinsky, 1996 ). On the other hand, neural networks, whether adaptive or hard-wired, have structures that shape population neural dynamics onto a low dimensional manifold, where nonrandom and ordered activity patterns emerge ( Ganguli et al, 2008 ; Harvey et al, 2012 ; Inagaki et al, 2018 ). Computational models have promised to provide a unified view of these observations ( Burak and Fiete, 2012 ; Brennan and Proekt, 2019 ; Mastrogiuseppe and Ostojic, 2018 ; Roberts et al, 2016 ), but a deep connection between theories and experiments remains to be established.…”

An orderly single-trial organization of population dynamics in premotor cortex predicts behavioral variability

“…These elaborate behavioral computations manifest in complex neural dynamics, and occur across multiple temporal scales and brain areas 1–11 . For example, recent studies in mice identified anterior lateral motor (ALM) cortex as a critical circuit node for perceptual decision tasks 9–12 . ALM neurons exhibit complex, heterogeneous, epoch-dependent dynamics; population dynamics in ALM and connected thalamic nuclei 13 evolve over time scales of milliseconds to seconds.…”