Hollis Lab

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Circuit Repair Laboratory

The Hollis lab studies the reorganization of neural circuits during rehabilitation. Our principal research focus is on the function of cortical motor networks after spinal cord injury. Our studies lie at the intersection of molecular biology and systems neuroscience, with an eye towards translation. We utilize optogenetic stimulation of, and optical recording from, cortical motor networks in order to understand the mechanisms that enable neural circuit remodeling after injury.

Spinal cord injury interrupts not only the transmission of neural signals within the spinal cord, but also disrupts the cortical networks responsible for interpreting and dictating those signals. A limited amount of endogenous dexterous motor recovery is possible, likely the result of a combination of corticospinal axon sprouting in close proximity to the lesion site, and of compensatory function from descending projections originating in the brainstem. The cortical mechanisms supporting this recovery are not understood, nor is it known whether limitations on cortical plasticity underlie the failure of current therapies to restore motor function. Regardless of the approach taken to alleviate the interruption of corticospinal axons, functional recovery will rely on the plasticity of the cortical motor network to incorporate the remodeled or replaced circuit. We are investigating the neuron intrinsic limitations on regeneration and the systems-level integration of circuit changes after spinal cord injury. Our goal is to develop novel therapeutic interventions that take advantage of cortical plasticity to promote recovery from spinal cord injury.

We are investigating the cortical response to spinal cord injury through the following distinct approaches:

  1. We are studying the ability of motor networks to incorporate regenerated axons after injury.
  2. We are examining how the molecular mechanisms of motor learning are engaged after spinal cord injury.
  3. We are determining the changes in intracortical architecture that occur in response to rehabilitation after spinal cord injury.
  4. We are testing an animal model of nerve transfer intervention to determine the limits on current clinical practice.
Hollis Lab: Motor cortex plasticity after spinal cord injury.

Motor cortex plasticity after spinal cord injury. Optical mapping of Thy1-channelrhodopsin mice, shows evoked motor maps (top insets). C5 spinal cord injury results in interruption of corticospinal axons (bottom insets). Early adaptation of maps after descending axon interruption shows increased forelimb flexor map (red) with concomitant reduction of motor responses caudal to C5. Rehabilitation coincident with corticospinal regenerative sprouting promotes motor map reorganization: expansion of proximal extensor maps into denervated hindlimb regions. Serradj, Agger, and Hollis Neurosci Lett 2017.

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Edmund R. Hollis II, Ph.D.

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