CENTER FOR NEUROSCIENCE IMAGING RESEARCH

CNIR Seminar

Title: Brain-wide networks of functionally distinct principal neurons in the primary somatosensory cortex

Abstract: Neuronal connections within and across brain areas provide the scaffolding for neural computations. Revealing brain-wide wiring diagrams at the single neuron level constitutes a fundamental step in understanding how distinct patterns of neuronal activity emerge and how these may support behavior. In primary sensory cortices, principal neurons exhibit heterogeneous patterns of activity not only in the presence but also, absence of external sensory stimulation, namely during spontaneous movements. Whether these behavioral-state dependent patterns of activity are supported by random or structured connectivity remains unknown. We show that movement-sensitive neurons receive characteristic excitatory long- range inputs. Using functional imaging, we monitored the activity of principal neurons in layers II/III of the mouse primary somatosensory cortex (S1). Activity during spontaneous movements was dominated by a subset of neurons, spatially intermingled with other functionally-distinct neurons. This subset was stable over time, suggestive of structured connectivity. To investigate brain-wide afferent connectivity onto functionally-defined, individual neurons, we combined functional imaging with single neuron-initiated monosynaptic retrograde tracing. Analysis of brain-wide, presynaptic anatomical ensembles revealed several connectivity features. First, each neuron, independently of activity profile, receives inputs from virtually every brain area known to project to S1. Second, local and long-range presynaptic ensembles of movement- sensitive and movement-insensitive neurons are not spatially distinct. Third, movement- sensitive neurons receive a smaller fraction of inputs from primary and secondary motor cortices, while receiving a larger fraction of inputs from thalamus than movement-insensitive neurons. Yet, the activity of movement-sensitive neurons cannot be explained by sensory feedback from moving whiskers, since it was preserved after unilateral whisker pad paralysis, nor by neuromodulatory inputs. Movement-triggered optogenetic suppression of thalamic inputs altered activity patterns, demonstrating a direct functional role of thalamic inputs in S1 during spontaneous movements. Our study provides an anatomical and functional connectivity rule that supports the representation of spontaneous movements in S1.