Mouse Motor Cortex Coordinates the Behavioral Response to Unpredicted Sensory Feedback

Abstract

SummaryMotor cortex (M1) lesions result in motor impairments, yet how M1 contributes to the control of movement remains controversial. To investigate the role of M1 in sensory guided motor coordination, we trained mice to navigate a virtual corridor using a spherical treadmill. This task required directional adjustments through spontaneous turning, while unexpected visual offset perturbations prompted induced turning. We found that M1 is essential for execution and learning of this visually guided task. Turn-selective layer 2/3 and layer 5 pyramidal tract (PT) neuron activation was shaped differentially with learning but scaled linearly with turn acceleration during spontaneous turns. During induced turns, however, layer 2/3 neurons were activated independent of behavioral response, while PT neurons still encoded behavioral response magnitude. Our results are consistent with a role of M1 in the detection of sensory perturbations that result in deviations from intended motor state and the initiation of an appropriate corrective response.

How a mouse licks a spout: Cortex-dependent corrections as the tongue reaches for, and misses, targets

“…These results predict that placing the spout very close to the mouth could rescue ALM-inactivation associated execution deficits. Experiments confirmed this prediction (SFig 8, Probability of contact, spout Close: Intact: 1 [1 1] vs ALM inactivated: 0.93 [0.72 0.96] p<0.05, n = 9 animals, Wilcoxon signed rank test), supporting the more general idea that motor cortical activity in mice is critical for online adjustments but not for cue-evoked movement initiation (25).…”

Cell-type specific outcome representation in primary motor cortex

“…Layer 2-3 neurons dramatically differ from layer 5 PT neurons in their input-output pattern, connectivity and intrinsic electrophysiological properties (Anderson et al, 2010;Harris and Shepherd, 2015;Hooks et al, 2011;Tsubo et al, 2013), thus it is not surprising that these different neuronal populations may perform different computations in motor cortex. Previous work has shown activity differences between layer 2-3 and layer 5 neurons Heindorf et al, 2018;Huber et al, 2012;Isomura et al, 2009;Komiyama et al, 2010;Masamizu et al, 2014), but here we report a new role of layer 2-3 neurons in generating performance outcome related signals during dexterous movements. An interesting hypothesis is that the observed separation of outcome evaluation (layer 2-3) and movement generation (layer 5) is beneficial in some way.…”

“…Neuronal activity which convey reward, reward prediction errors, and performance error signals are ubiquitous in the brain and have been described in various brain regions including midbrain, cerebellum, and cortical regions (Amador et al, 2000;Amiez et al, 2006;Chen et al, 2017;Heffley et al, 2018;Heindorf et al, 2018;Isomura et al, 2013;Keller et al, 2012;Kostadinov et al, 2019;Krigolson and Holroyd, 2007;Laubach et al, 2000;Mathis et al, 2017;Matsumoto et al, 2007;Olson, 2004, 2005;Sajad et al, 2019;Schall et al, 2002;Schultz, 2000;Shadmehr and Krakauer, 2008;Stuphorn et al, 2000;Teichert et al, 2014;Wallis and Kennerley, 2010;Watabe-Uchida et al, 2017;Wickens et al, 2003). Such signals were shown to serve in error-based and reinforcement learning behavioral paradigms (Glascher et al, 2010;Mathis et al, 2017;Shadmehr and Krakauer, 2008;Wolpert et al, 2011) and such combined signals can enhance adaptation (Galea et al, 2015;Nikooyan and Ahmed, 2015).…”

Context-dependent limb movement encoding in neuronal populations of motor cortex

“…M1 L2/3 receives input from other cortical areas such as the somatosensory cortex 32,33 and the secondary motor area M2 [34][35][36] , which is thought to organize flexible motor behavior and to link relevant context information to motor processing, similar to the primate supplementary complex [37][38][39] . Neuronal populations in M1 L2/3 also send excitatory projections to M1 output neurons in layer 5 40,41 whereby they can couple sensory information to motor output 42,44,63 . Our finding that silencing the M2 to M1 projections abolishes contextdependent modulation of movement encoding in M1 L2/3 suggests that M1 L2/3 learns to exploit contextual information from M2 to selectively route sensory information from those joints into corticospinal circuits, which require flexible readjustments in the given environment.…”