Phillips, J. W. | bioRxiv Science

bioRxiv2018

Motor cortex can modulate somatosensory processing via cortico-thalamo-cortical pathway

The somatosensory and motor systems are intricately linked, providing several routes for the sensorimotor interactions necessary for haptic processing. Here, we used electrical and optogenetic stimulation to study the circuits that enable primary motor cortex (M1) to exert top-down modulation of whisker-evoked responses, at the levels of brain stem, thalamus and somatosensory cortex (S1). We find that activation of M1 drives somatosensory responsive cells at all levels, and that this excitation is followed by a period of tactile suppression, which gradually increases in strength along the ascending somatosensory pathway. Using optogenetic stimulation in the layer-specific Cre driver lines, we find that activation of layer VI cortico-thalamic neurons is sufficient to drive spiking in higher order thalamus, and that this is reliably followed by excitation of S1, suggesting a cross-modal cortico-thalamo-cortical pathway. Cortico-thalamic excitation predicts the degree of subsequent tactile suppression, consistent with a strong role for thalamic circuits in the expression of inhibitory sensorimotor interactions. These results provide evidence of a role for M1 in dynamic modulation of S1, largely under cortico-thalamic control.

neuroscience↗

bioRxiv2017

A topographic axis of transcriptional identity in thalamus

Uncovering common principles by which diverse modalities of information are processed is a fundamental goal in neuroscience. In mammalian brain, thalamus is the central processing station for inputs from sensory systems, subcortical motor systems, and cortex; a function subserved by over 30 defined nuclei1,2. Multiple thalamic nuclei send convergent information to each region of the forebrain, but whether there is a conserved architecture across the set of thalamic pathways projecting to each forebrain area has remained unresolved3-5. To uncover organizational principles of thalamic pathways, we produced a near-comprehensive transcriptomic atlas of thalamus. This revealed a common logic for thalamic nuclei serving all major cortical modalities. We found that almost all nuclei belong to one of three major profiles, with a given cortical area getting input from each of these profiles. These profiles lie on a single axis of variance aligned with the mediolateral axis of thalamus, and this axis is strongly enriched in genes encoding receptors and ion channels. We further show that each projection profile exhibits different electrophysiological signatures. Single-cell profiling revealed that rather than forming discrete classes, thalamic neurons lie on a spectrum, with intermediate cells existing between profiles. Thus, in contrast to canonical models of thalamus that suggest it is a switchboard primarily concerned with routing distinct modalities of information to distinct cortical regions, we show that the thalamocortical system is more akin to a molecularly-defined filter bank repeatedly applied across modality. Together, we reveal striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.

neuroscience↗