Distinct Contributions of Whisker Sensory Cortex and Tongue-Jaw Motor Cortex in a Goal-Directed Sensorimotor Transformation

The neural circuits underlying goal-directed sensorimotor transformations in the mammalian brain are incompletely understood. Here, we compared the role of primary tongue-jaw motor cortex (tjM1) and primary whisker sensory cortex (wS1) in head-restrained mice trained to lick a reward spout in response to whisker deflection. Two-photon microscopy combined with microprisms allowed imaging of neuronal network activity across cortical layers in transgenic mice expressing a genetically encoded calcium indicator. Early-phase activity in wS1 encoded the whisker sensory stimulus and was necessary for detection of whisker stimuli. Activity in tjM1 encoded licking direction during task execution and was necessary for contralateral licking. Pre-stimulus activity in tjM1, but not wS1, was predictive of lick direction and contributed causally to small preparatory jaw movements. Our data reveal a shift in coding scheme from wS1 to tjM1, consistent with the hypothesis that these areas represent cortical start and end points for this goal-directed sensorimotor transformation.

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

Carl Petersen, Varun Sreenivasan

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.

Wiley-Blackwell2015

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

Two-photon calcium imaging of neocortical projection neurons in whisker somatosensory cortex during goal-directed sensorimotor learning

Dimitra Angeliki Vavladeli

Abstract Excitatory projection neurons of the neocortex are thought to play important roles in per-ceptual and cognitive functions of the brain by directly connecting diverse cortical and subcortical areas. However, many aspects of the anatomical and functional organization of these inter-areal connections are unknown. The mouse primary somatosensory whisk-er barrel cortex (S1) serves as an important model for investigating the mammalian neo-cortex, and, here, I firstly investigate the structure and secondly the function of a specific subset of S1 cortico-cortical long-range projection neurons. In the first part of my thesis, I studied long-range axonal projections of excitatory layer 2/3 neurons with cell bodies located in S1. As a population, these neurons densely projected to secondary whisker somatosensory cortex (S2) and primary/secondary whisker motor cortex (M1/2), with additional axon in the dysgranular zone surrounding the barrel field, perirhinal temporal association cortex and striatum. The execution of a goal-directed behavior requires the brain to process incoming sensory information from the environment in a context-, learning- and motivation-dependent manner in order to perform specific motor actions. Cortico-cortical communica-tion in the context of goal-directed sensorimotor transformation has begun to be studied, but little is known about how signaling between interconnected cortical areas is modified by sensorimotor learning, as well as in response to changes in reward contingencies. Hence, in the second part of my thesis, I studied cortico-cortical dynamics in primary whisker somatosensory barrel cortex (S1) of mice during a combined whisker and audito-ry task. Using transgenic mice expressing GCaMP6f combined with two-photon micros-copy and retrograde labeling techniques, I chronically monitored the activity of excitatory layer 2/3 neurons in S1 projecting to M1 or S2, while mice learned the behavioral switch task. The results demonstrated that both classes of neurons responded after whisker and auditory stimulation. However, the whisker stimulus evoked response was stronger than the auditory stimulus evoked response. Neurons projecting to S2 exhibited stronger re-sponses compared to neurons projecting to M1 neurons. Those responses remained rela-tively stable across training sessions and under different reward conditions. Furthermore, both classes of neurons responded during spontaneous licking, but neurons projecting to S2 had larger licking-related responses compared to neurons projecting to M1. This work therefore furthers our knowledge of the structure and function of specific types of cortical projection neurons, which is a necessary step towards detailed under-standing of how sensory information might be signaled from primary sensory areas to downstream brain regions for further processing.

EPFL2018

Two-photon calcium imaging of neocortical projection neurons in whisker somatosensory cortex during goal-directed sensorimotor learning

Dimitra Angeliki Vavladeli

EPFL2018