Kentucky Spinal Cord Injury Research Center

Jeffrey Petruska, Ph.D.

Assistant Professor
Department of Anatomical Sciences & Neurobiology
Department of Neurological Surgery

Biography

Recent Publications

Contact

Laboratory of Neural Physiology and Plasticity

Research

In terms of biological principles, we investigate the cellular and molecular mechanisms regulating anatomical and electrophysiological plasticity of neurons, focusing on the peripheral nervous system and spinal cord. We are particularly interested in the interaction between, and co-regulation of, the anatomical and electrophysiological properties of neurons. We study these principles in the context of the spinal pain system and spinal cord injury.

In terms of biomedical questions, we investigate:

1) Effects of spinal cord injury and post-SCI treatments on the function of motor and sensory neurons

2) Mechanisms and consequences of sensory neuron responses to tissue damage

These hypothesis-driven projects are well-coordinated when viewed in the context of my long-term vision – understanding how sensory input to the spinal cord below an injury influences the function of the remaining circuitry. It is my proposition that the combined effects of spinal cord injury and inflammatory secondary conditions act in concert to induce “circuit dysfunction” in the spinal cord caudal to an injury due to an unchecked, overactive, and highly plastic spinal nociceptive system. Unfortunately, SCI-related secondary conditions are rarely considered in basic neuroscience research, in spite of their high degree of clinical relevance and importance to the SCI community. On the other hand, the status of spinal circuits below an injury is a topic of a great deal of basic science study, but principally in the context of acute lacerations intended to determine the role of specific tracts, and much less-so in the context of clinically-modelled SCI. The status of these circuits after SCI is increasingly more important with the accumulation of data demonstrating the efficacy of activity-dependent task-specific training (i.e., physical therapy), and the reliance of that therapy on both appropriate sensory input and “healthy” caudal spinal cord circuitry.

Biomedical hypothesis-driven projects

1) Effects of spinal cord injury and post-SCI treatments on motoneuron function

This project investigates the effects of graded contusion SCI on the electrophysiological properties of hindlimb motoneurons. Secondarily, the electrophysiological parameters of motoneurons are related directly (i.e. from the same animals) to behavioral measures (step/swim kinematics, weight-support capacity) and molecular measures (levels of neurotrophins and neurotrophin receptors in relevant muscles, DRG, and spinal cord segments). Further, we determine the effects of post-SCI viral vector-mediated delivery of neurotrophic factors on these same parameters.

2) Mechanisms and consequences of sensory neuron responses to tissue damage

This project investigates the mechanisms by which sensory neurons innervating injured/inflamed tissue are induced to express injury/regeneration-like genes. It also investigates the effects of this gene expression on the anatomical and electrophysiological properties of the affected sensory neurons.

3) Mechanisms and consequences of adult axonal collateral sprouting

This project investigates the molecular-level regulation of adult axonal collateral sprouting – the extension of new axonal branches from non-injured neurons. Putative regulatory factors and pathways were identified principally from analysis of the transcriptome (mRNA microarray) using a “spared dermatome” model, where non-injured sensory neurons extend their axons into adjacent denervated skin. This project has identified factors regulated specifically in sprouting, as opposed to regeneration, which represent a rational pathway from external signal to internal cytoskeletal response and transcriptional regulation.

Projects developing model systems and tools

1) “Functional reporter” gene for use with intracellular electrophysiology

This project aims to develop “functional reporters” – genes that can report on the genetic status of single cells to electrophysiological probes independent of optical detection. For example, frequently-used reporters such as GFP are undetectable by electrodes. Further, for applications such as in vivo electrophysiology in rodents and larger animals many targets are simply too deep to employ microscopy in parallel with electrophysiology. Thus, to enhance the throughput and analytical power of “blind” single-cell electrophysiology, I am developing a reporter gene that will signal in real time in a manner detectible by intracellular electrodes.

2) CTM reflex as a model system

This project characterizes the organization of the cutaneus trunci muscle (CTM) reflex system and develops it as a model system for testing hypotheses, particularly those related to spinal nociception/pain, propriospinal neuron function, and plasticity in sensory and motor neurons. It is already validated as a monitor for sensory neuron collateral sprouting through skin and for efficacy of anesthetic and analgesic agents.