Contact

Department

Cellular and Integrative Physiology

Jeffery A. Boychuk, Ph.D

Assistant Professor

Education

B.Sc., University of Lethbridge, 2005
Ph.D., University of Florida, 2009

Research

Neural Circuit Reorganization of Cortical Structures in Response to Experience and Injury.

We are dedicated to treating the brain after mechanical and vascular trauma in order to improve lives affected by stroke, traumatic brain injury and epilepsy.

Overview: Cortical neurons exhibit profound forms of molecular, structural and biophysical remodeling during learning and following injury to the brain. Our laboratory studies how neural circuits in neocortex and hippocampus are affected by these processes. We seek to understand the function of these circuits and to test how they are modified by brain insults and subsequent interventions. It is an exciting era for this research because of the rapid innovation in transcriptome/proteome profiling, neuroanatomical tracing techniques and mouse genetics. These approaches provide a means to more precisely define populations of cells and to identify how neurons directly signal to one another. This increased level of specificity dramatically increases the number of opportunities to probe these networks in a highly focused manner. Our contribution is to combine these innovations with modern, and emerging, cell patch clamp electrophysiological techniques in order to generate comprehensive data sets of neuronal signaling within these defined cell networks. The central goal of this work is to identify the discrete circuit changes responsible for brain repair. This is carried out in order to generate novel therapeutic targets that can be harnessed to optimize brain recovery.

Motor Cortex & Stroke: Neocortex exhibits a laminar organization that contains several subtypes of glutamatergic-expressing and gamma-aminobutyric (GABA)-expressing cells. Several laboratories have been making key discoveries to identify the circuit architecture of these cells both within and between these cortical layers. We are contributing to this endeavor by directly measuring these circuits in the context of motor learning, ischemic injury and post-injury rehabilitative training. These projects are heavily guided by our previous investigations of large network reorganization of motor cortex during recovery. Previous topics include neuromodulation strategies as well as testing for the roles of serotonin signaling, chloride co-transport and hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in motor cortex dynamics. Recent collaborative efforts have tested the possibility that treatments designed to provide neuroprotection after stroke may also confer brain repair benefits.

Hippocampus & Traumatic Brain Injury/Post-Traumatic Epilepsy: The dentate gyrus (DG) is a site of converging input, and its principle cells, dentate granule cells (DGCs), exhibit properties that make them well suited to restrict excitability and filter incoming signals. Thus, DGCs are often considered a gating mechanism within the hippocampus. We are testing whether preserving or restoring DG function after trauma can support recovery while reducing the likelihood of post-traumatic epilepsy. This work studies structural and physiological modifications both in DGCs and in inhibitory GABA-expressing cells that innervate them. Recent experiments have tested for beneficial effects of pharmacologically inhibiting mammalian (mechanistic) target of rapamycin (mTOR) as well as modifying type A GABA receptor subunit expression.

 

 

 

Publications

HCN channels segregate stimulation-evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents.
Boychuk JA, Farrell JS, Palmer LA, Singleton AC, Pittman QJ, Teskey GC.
J Physiol. 2017 Jan 1;595(1):247-263. doi: 10.1113/JP273068. Epub 2016 Sep 27.
PMID:27568501

Loss of HCN channel mediated Ih current following seizures accounts for movement dysfunction.
Boychuk JA, Teskey GC.
Channels (Austin). 2017 May 4;11(3):176-177. doi: 10.1080/19336950.2016.1256517. Epub 2016 Nov 4. No abstract available.
PMID:27813693

Brain in injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons is Differentially Suppressed by Rapamycin
Butler CR*, Boychuk JA*, Smith BN.
eNeuro. 2017. doi: 10.1523/ENEURO.0134-17.2017. Epub 2017 September 25.
*CRB and JAB contributed equally to this work.

Enhanced Motor Recovery After Stroke With Combined Cortical Stimulation and Rehabilitative Training Is Dependent on Infarct Location.
Boychuk JA, Schwerin SC, Thomas N, Roger A, Silvera G, Liverpool M, Adkins DL, Kleim JA.
Neurorehabil Neural Repair. 2016 Feb;30(2):173-81. doi: 10.1177/1545968315624979. Epub 2015 Dec 29.
PMID:26719353

Enduring changes in tonic GABAA receptor signaling in dentate granule cells after controlled cortical impact brain injury in mice.
Boychuk JA, Butler CR, Halmos KC, Smith BN.
Exp Neurol. 2016 Mar;277:178-189. doi: 10.1016/j.expneurol.2016.01.005. Epub 2016 Jan 6.
PMID:26772635

Differential effects of rapamycin treatment on tonic and phasic GABAergic inhibition in dentate granule cells after focal brain injury in mice.
Butler CR, Boychuk JA, Smith BN.
Exp Neurol. 2016 Jun;280:30-40. doi: 10.1016/j.expneurol.2016.03.022. Epub 2016 Mar 25.
PMID:27018320

Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.
Hussin AT, Boychuk JA, Brown AR, Pittman QJ, Teskey GC.
Brain Stimul. 2015 Jul-Aug;8(4):742-50. doi: 10.1016/j.brs.2015.03.003. Epub 2015 Mar 27.
PMID:25892002

Effects of Rapamycin Treatment on Neurogenesis and Synaptic Reorganization in the Dentate Gyrus after Controlled Cortical Impact Injury in Mice.
Butler CR, Boychuk JA, Smith BN.
Front Syst Neurosci. 2015 Nov 27;9:163. doi: 10.3389/fnsys.2015.00163. eCollection 2015.
PMID:26640431

Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.
Xu H, Boychuk JA, Boychuk CR, Uteshev VV, Smith BN.
J Neurophysiol. 2015 Feb 15;113(4):1165-74. doi: 10.1152/jn.00614.2014. Epub 2014 Nov 26.
PMID:25429117

Serotonin 1A receptors alter expression of movement representations.
Scullion K*, Boychuk JA*, Yamakawa GR, Rodych JT, Nakanishi ST, Seto A, Smith VM, McCarthy RW, Whelan PJ, Antle MC, Pittman QJ, Teskey GC.
J Neurosci. 2013 Mar 13;33(11):4988-99. doi: 10.1523/JNEUROSCI.4241-12.2013.
PMID:23486969
*KS and JAB contributed equally to this work.

Distributed versus focal cortical stimulation to enhance motor function and motor map plasticity in a rodent model of ischemia.
Boychuk JA, Adkins DL, Kleim JA.
Neurorehabil Neural Repair. 2011 Jan;25(1):88-97. doi: 10.1177/1545968310385126. Epub 2010 Nov 9.
PMID:21062949

Rat models of upper extremity impairment in stroke.
Kleim JA, Boychuk JA, Adkins DL.
ILAR J. 2007;48(4):374-84. Review.
PMID:17712223

Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord.
Adkins DL, Boychuk J, Remple MS, Kleim JA.
J Appl Physiol (1985). 2006 Dec;101(6):1776-82. Epub 2006 Sep 7. Review.
PMID:16959909

Neural circuit mechanisms of post-traumatic epilepsy.
Hunt RF, Boychuk JA, Smith BN.
Front Cell Neurosci. 2013 Jun 18;7:89. doi: 10.3389/fncel.2013.00089. eCollection 2013.
PMID:23785313