Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice

Mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers. Optogenetic stimulation of wS1 drove retraction of contralateral whiskers while stimulation of wM1 drove rhythmic whisker protraction. To map brainstem pathways connecting these cortical areas to whisker motor neurons, we used a combination of anterograde tracing using adenoassociated virus injected into neocortex and retrograde tracing using monosynaptic rabies virus injected into whisker muscles. Our data are consistent with wS1 driving whisker retraction by exciting glutamatergic premotor neurons in the rostral spinal trigeminal interpolaris nucleus, which in turn activate the motor neurons innervating the extrinsic retractor muscle nasolabialis. The rhythmic whisker protraction evoked by wM1 stimulation might be driven by excitation of excitatory and inhibitory premotor neurons in the brainstem reticular formation innervating both intrinsic and extrinsic muscles. Our data therefore begin to unravel the neuronal circuits linking the neocortex to whisker motor neurons.

Motor Control in the Mouse Whisker System

Varun Sreenivasan

The motor systems of the mammalian brain are a remarkable product of many millions of years of evolution. It is the motor systems that make us and other mammals mobile, that guide our actions in response to sensory information and conversely modulate the very nature of the sensory input that our brain receives. The mystacial vibrissae or whiskers present on the face of mice are important sensors that provide high resolution tactile information to the brain. Whereas the pathways that are involved in signaling and processing sensory information from the whiskers have been the subject of intense investigation for many years, we know relatively little about how whisker movements are controlled by the brain. In the first part of the thesis, I present evidence for two parallel pathways originating from the neocortex that control antagonistic movements of the whiskers. I first describe whisker movements elicited upon Channelrhodopsin-2 (ChR2) stimulation of whisker somatosensory cortex (wS1) and whisker motor cortex (wM1). At short latencies, optogenetic stimulation of wS1 drove whisker retraction while optogenetic stimulation of wM1 drove rhythmic whisker protraction. Next, using recent developments in Rabies virus retrograde tracing, I mapped the location of the motor neurons in the facial nucleus, finding two distinct neuron pools for the extrinsic (retractor) muscle Nasolabialis and the intrinsic (protractor) follicular muscle. These distinct motor neuron populations received premotor input from different sources in the brainstem. While the premotor neurons of the extrinsic muscle were located more densely in the spinal trigeminal nucleus (Sp5), the premotor neurons of the intrinsic muscle were located more densely in the reticular formation (Rt). Anterograde tracing from wS1 and wM1 cortex revealed a complementary distribution of axons in the brainstem. Whereas wS1 strongly innervated Sp5, wM1 innervated the Rt. These data therefore begin to unravel the circuitry from the neocortex to the whisker motor neurons. In the second part of the thesis, I investigated the subthreshold and spiking correlates of whisker movements using whole-cell current clamp recordings of individual excitatory neurons in wM1. Brief 1 ms optogenetic stimulation of wS1 elicited rhythmic whisking after long latencies which was abolished upon pharmacological inactivation of wM1. Whole-cell recordings in wM1 during wS1 stimulation showed that the long-range synaptic input from wS1 to wM1 is encoded as a bi-phasic membrane potential response with an early depolarizing post-synaptic potential (Dep. PSP), followed by a hyperpolarizing post-synaptic potential (Hyp. PSP) in individual wM1 neurons. Approximately 150 ms after the wS1 stimulus, the Vm showed a rebound depolarization, which, on most trials, was followed by late rhythmic whisking. Whole-cell recordings during self-generated whisker movements showed that upon whisking, wM1 undergoes a profound cortical state change, where the mean Vm is more depolarized, slow fluctuations of the Vm are reduced and spike rates in layer 5 increase. Aligning the membrane potential trajectories to the onset of whisker movement epochs revealed that changes in Vm occurred almost 100 ms before movement onset. Finally, an examination of the Vm dynamics during rhythmic whisking showed that the Vm of individual wM1 neurons is modulated by the phase of the whisk cycle. This modulation is stronger in layer 2/3 compared to layer 5.

EPFL2015

Target-specific membrane potential dynamics of neocortical projection neurons during goal-directed behavior

Carl Petersen, Takayuki Yamashita

Goal-directed behavior involves distributed neuronal circuits in the mammalian brain, including diverse regions of neocortex. However, the cellular basis of long-range cortico-cortical signaling during goal-directed behavior is poorly understood. Here, we recorded membrane potential of excitatory layer 2/3 pyramidal neurons in primary somatosensory barrel cortex (S1) projecting to either primary motor cortex (M1) or secondary somatosensory cortex (S2) during a whisker detection task, in which thirsty mice learn to lick for water reward in response to a whisker deflection. Whisker stimulation in 'Good performer' mice, but not 'Naive' mice, evoked long-lasting biphasic depolarization correlated with task performance in S2-projecting (S2-p) neurons, but not M1-projecting (M1-p) neurons. Furthermore, S2-p neurons, but not M1-p neurons, became excited during spontaneous unrewarded licking in 'Good performer' mice, but not in 'Naive' mice. Thus, a learning-induced, projection-specific signal from S1 to S2 may contribute to goal-directed sensorimotor transformation of whisker sensation into licking motor output.

Elife Sciences Publications Ltd2016

Cell-type-specific nicotinic input disinhibits mouse barrel cortex during active sensing

Sylvain Crochet, Célia Roxane Gasselin, Benoît Hohl, Carl Petersen

Fast synaptic transmission relies upon the activation of ionotropic receptors by neurotransmitter release to evoke postsynaptic potentials. Glutamate and GABA play dominant roles in driving highly dynamic activity in synaptically connected neuronal circuits, but ionotropic receptors for other neurotransmitters are also expressed in the neocortex, including nicotinic receptors, which are non-selective cation channels gated by acetylcholine. To study the function of non-glutamatergic excitation in neocortex, we used two-photon microscopy to target whole-cell membrane potential recordings to different types of genetically defined neurons in layer 2/3 of primary somatosensory barrel cortex in awake head-restrained mice combined with pharmacological and optogenetic manipulations. Here, we report a prominent nicotinic input, which selectively depolarizes a subtype of GABAergic neuron expressing vasoactive intestinal peptide leading to disinhibition during active sensorimotor processing. Nicotinic disinhibition of somatosensory cortex during active sensing might contribute importantly to integration of top-down and motor-related signals necessary for tactile perception and learning.

CELL PRESS2021

Motor Control in the Mouse Whisker System

Varun Sreenivasan

EPFL2015