Multisensory Signaling Shapes Vestibulo-Motor Circuit Specificity

Abstract

The ability to continuously adjust posture and balance is necessary for reliable motor behavior. Vestibular and proprioceptive systems influence postural adjustments during movement by signaling functionally complementary sensory information. Using viral tracing and mouse genetics, we reveal two patterns of synaptic specificity between brainstem vestibular neurons and spinal motor neurons, established through distinct mechanisms. First, vestibular input targets preferentially extensor over flexor motor pools, a pattern established by developmental refinement in part controlled by vestibular signaling. Second, vestibular input targets slow-twitch over fast motor neuron subtypes within extensor pools, while proprioceptors exhibit inversely correlated connectivity profiles. Genetic manipulations affecting the functionality of proprioceptive feedback circuits lead to adjustments in vestibular input to motor neuron subtypes counterbalancing the imposed changes, without changing the sparse vestibular input to flexor pools. Thus, two sensory signaling systems interact to establish complementary synaptic input patterns to the final site of motor output processing.

Comprehensive Monosynaptic Rabies Virus Mapping of Host Connectivity with Neural Progenitor Grafts after Spinal Cord Injury

“…Collectively, vestibulospinal projections constituted 8% of supraspinal projections to the graft (Figures 3L and 3M). Vestibulospinal neurons make monosynaptic contacts onto premotor spinal interneurons (Bourane et al., 2015), and the lateral vestibular nucleus (LVe) innervates motor neurons at lumbar levels of the spinal cord (Basaldella et al., 2015). …”

Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing

“…W. Yang et al, 2009). SST cINs in the primary somatosensory cortex (S1) were targeted using AAV viral injections in mice carrying an SST Cre allele and a conditional compound synaptophysin1-eGFP (Syp-eGFP) construct, which functions as a presynaptic reporter (i.e SST cre ;R26R Figure1A) (Basaldella et al, 2015;Li et al, 2010;Wamsley et al, 2018). To modulate the activity of SST cINs, these mice were injected at P0 with Cre-dependent AAVs that drive the expression of either KIR2.1 or NaChBac channels along with an mCherry reporter ( Figure 1A, B).…”

Organization and function of neuronal circuits controlling movement

“…Since this motor neuron subclass is recruited for postural tasks, the revealed specific connectivity matrix from brainstem vestibular neurons thus matches perfectly this behavioral requirement. We found that the precision of these synaptic connections is established during development and requires multisensory signaling from both vestibular and proprioceptive sources (Basaldella et al , ). A third example of a functionally dedicated pathway was described in a recent collaborative study, in which we identified specific neurons in the periaqueductal gray in the midbrain involved in the regulation of defensive behavior, signaling through the caudal brainstem nucleus Mc (Tovote et al , ).…”

“… (A) Scheme displaying brainstem nuclei with neurons premotor to forelimb (FL) and hindlimb (HL)‐innervating spinal motor neurons in different colors (adapted from Esposito et al , ); especially highlighted are MdV, needed for efficient forelimb grasping, and the vestibular nucleus (Ve), with a role in posture and balance. (B) Connectivity between neurons in the vestibular nucleus and hindlimb‐innervating motor neurons (adapted from Basaldella et al , ). Note that Ve input is biased to extensor over flexor motor neurons (interpool specificity) and within the extensor pool to slow over fast motor neurons (intrapool specificity).…”

“…Most notably, we traced the defect specifically to the grasping phase of the unilateral forelimb behavior (Fig A), and no deficiency was found in the reaching phase toward the food pellet or the retrieval phase back to the mouth (Esposito et al , ). A second topic we studied is the connectivity from the vestibular nucleus to hindlimb‐innervating motor neurons (Basaldella et al , ). As previously found in cats, these synaptic inputs are directed preferentially to extensor over flexor hindlimb‐innervating motor neurons also in mice, but within extensor motor neuron pools, synaptic inputs are targeted in high number to slow‐ over fast type motor neurons (Fig B).…”