Biology subjects

Pop, I. V.

Publications and source records attributed to Pop, I. V..

3 recordsLinked to original sources

bioRxiv2022

Electrophysiological properties of neurons in the intermediate thoracolumbar spinal cord mediating proprioception.

Animals must know where their body is in relationship to their environment to move appropriately. Proprioception, the sense of limb and body position, is required to produce feedforward predictions of future movement as well as provide feedback information during movement to update the system. How proprioception is processed at the level of the spinal cord is not well understood. Most work has focused on Clarkes column (CC) neurons, a component of the dorsal spinocerebellar tract (DSCT). CC neurons receive hindlimb proprioceptive information and send it directly to the cerebellum with no axon collaterals to other neurons in the spinal cord. In contrast to CC neurons, we previously found that a subset of thoracolumbar Atoh1-lineage neurons also receives proprioceptive afferent inputs, but project locally within the spinal cord including synapsing on motor neurons. We set out to understand how CC and Atoh1-lineage neurons in the thoracolumbar spinal cord respond to electrical activity. Using in vitro acute spinal cord slices and whole-cell patch clamp, we characterized the passive and active electrical properties of CC and thoracolumbar Atoh1-lineage neurons. We find that most CC neurons increase their action potential firing frequency linearly upon increased current injection up to high frequencies likely due to a hyperpolarization-activated current (Ih). In contrast, most Atoh1-lineage neurons do not have an Ih current and therefore, their firing frequency fades with increasing current injection. Interestingly, although Atoh1-lineage neurons are classically subdivided into a contralaterally-projecting Medial and ipsilaterally-projecting Lateral population, we find no obvious electrophysiological signatures that could distinguish these spatially distinct populations. Finally, we set out to determine the organization of the inputs to CC and Atoh1-lineage neurons. In a hemisected spinal cord preparation, while recording from neurons in the lower thoracic to upper lumbar segments, we find that CC neurons receive low threshold inputs (proprioceptive or low threshold mechanoreceptor) from lumbar 2 to 4 dorsal roots, while Atoh1-lineage Medial neurons do not. This raises the possibility that Atoh1-lineage Medial neurons receive proprioceptive inputs from more local dorsal roots. Altogether, we find that CC and Atoh1-lineage neurons have distinct membrane properties and sensory input organization even though they are both reported to receive proprioceptive information and are in close proximity in lamina V-VII of the thoracolumbar spinal cord.

neuroscience↗

bioRxiv2020

Evidence for genetically distinct direct and indirect spinocerebellar pathways mediating proprioception.

Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways are wired. Defining the anatomy of secondary neurons in the spinal cord that integrate and relay proprioceptive and potentially cutaneous information from the periphery to the cerebellum is fundamental to understanding how proprioceptive circuits function. Here, we use genetic tools in both male and female mice to define the unique anatomical trajectories of long-range direct and indirect spinocerebellar pathways as well as local intersegmental spinal circuits. We find that Clarkes column (CC) neurons, a major contributor to the direct spinocerebellar pathway, has mossy fiber terminals that diversify extensively in the cerebellar cortex with axons terminating bilaterally, but with no significant axon collaterals within the spinal cord, medulla, or cerebellar nuclei. By contrast, we find that two of the indirect pathways, the spino-lateral reticular nucleus (spino-LRt) and spino-olivary pathways, are in part, derived from cervical Atoh1-lineage neurons, while thoracolumbar Atoh1-lineage neurons project mostly locally within the spinal cord. Notably, while cervical and thoracolumbar Atoh1-lineage neurons connect locally with motor neurons, no CC to motor neuron connections were detected. Silencing of caudal Atoh1- lineage neurons results in a subtle motor impairment consistent with a defect in local proprioceptive circuitry. Altogether, we define anatomical differences between long-range direct, indirect, and local proprioceptive subcircuits that likely mediate different components of proprioceptive-motor behaviors. Significance StatementWe define the anatomy of long-range direct and indirect spinocerebellar pathways as well as local spinal proprioceptive circuits. We observe that mossy fiber axon terminals of Clarkes column (CC) neurons diversify proprioceptive information across granule cells in multiple lobules on both ipsilateral and contralateral sides sending no significant collaterals within the spinal cord, medulla, or cerebellar nuclei. Strikingly, we find that cervical spinal cord Atoh1-lineage neurons form mainly the indirect spino- lateral reticular nucleus and spino-olivary tracts and thoracolumbar Atoh1-lineage neurons project locally within the spinal cord while only a few Atoh1-lineage neurons form a direct spinocerebellar tract. Altogether, we define the development, anatomical projections, and some behavioral consequences of silencing spinal proprioceptive pathways.

neuroscience↗

bioRxiv2020

Motor neurons involved in fine motor control are labeled by tracing Atoh1-lineage neurons in the spinal cord

Motor neurons (MNs) innervating the digit muscles of the intrinsic hand and foot (IH and IF) control fine motor movements. Previous studies suggest that the IH and IF MN pools have a unique developmental history in comparison to limb MN pools. Consistent with having this unique development, we find that the IH and IF MN pools are labeled postnatally using a CRE knock-in mouse line of Atoh1, a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, while limb-innervating MN pools are not. Approximately 60% of the IH and IF MN pools are labeled and are a mixture of alpha and gamma-MNs. In addition, because Atoh1 is known developmentally to specify many cerebellar-projecting neurons, we tested the hypothesis that IH and IF MNs can send axon collaterals to the cerebellum as a mechanism of corollary discharge. Using intersectional genetic, viral labeling, and retrograde labeling strategies, we were unable to provide evidence in support of this idea. As a secondary finding of our viral labeling experiments, we report here that injection of both AAV and Lentiviruses in the periphery can cross the blood-brain barrier to infect Purkinje cells within the central nervous system. Altogether, though, we find that labeling of the IH and IF motor neurons using the Atoh1 CRE knock-in mouse suggests that IH and IF MNs have a unique developmental history and that this mouse strain might be a useful tool to target these specific sets of neurons allowing for functional studies of fine motor control. Significance StatementMotor neurons (MNs) of the intrinsic hand and foot (IH and IF) are labeled postnatally using a CRE knock-in mouse line of the basic helix-loop-helix (bHLH) transcription factor Atoh1 indicating a unique developmental history. We tested whether IH and IF MNs send axon collaterals rostrally to the cerebellum as a mechanism of direct corollary discharge from MNs, but the question remains unresolved. As a resource for the community, we report that injection of both AAV and Lentiviruses in the periphery can cross the blood-brain barrier and infect Purkinje cells within the central nervous system.

developmental biology↗