Katinka Stecina, Ph.D.
Assistant Professor, Physiology & Pathophysiology
University of Manitoba
- The in vivo, adult mouse lab in my laboratory is a unique development in the field of neuroscience: it is using a combination of classical electrophysiological techniques for brains stimulation and intraspinal recording of neural activity. The electrophysiology data and post-hoc neuroanatomical methods to identify the stimulated and/or the recorded regions is used to improve our understanding on the organization of spinal cord circuits involved in the generation of motor actions and the sensory control of locomotion.
The interactions between the brain and spinal interneuron classes (some related to the central pattern generator network) and the interneurons contributing to autonomic functions are the two main lines of research in my lab. My work is mainly basic science studies with potential future implications and breakthroughs in the rehabilitation of motor function following injury to the central nervous system, including spinal cord injury or stroke.
The current research projects are the following:
- Characterization of adult commissural neurons in the murine lumbar segments: the goal is to utilize activity dependent labeling based on a the cfos early gene activation driven expression of enhanced green fluorescent protein in a genetically modified strain of mice (cfos-EGFP mice). These animals have been successfully used for labeling of locomotor-related spinal neurons in neonatal animals, and the applications of similar methods followed by cellular-level investigations of the green networks in decerebrate animals during fictive locomotor activity have been also successful. During these studies, we aim to develop a way to label neurons being activated during a crossed-extension reflex, which is a smaller scale network (and probably of sub-set of) that related to locomotion. This work has been further supported by the Discovery grant program from NSERC (2015- 2020) and novel activity dependent markers are to be tested soon in relation to this project. In addition, optogenetic tools for selective activation of distinct neuronal circuits will be used in mature, murine spinal networks in the in vivo electrophysiology laboratory with capabilities for studying functionally mature mouse spinal cords in an integrated stereotaxic brain and spinal frame. In decerebrated mice, motor output can be generated in several ways, including via reflex and voluntary loops. By the use of optical stimulation applied to the cholinergic interneurons, their ability to generate locomotor output or to modify already existing locomotor activity and the output of voluntary or reflex loop induced activity will be investigated.
- The interplay between orexinergic and monoaminergic transmission in the spinal cord (in collaboration with Dr. Jordan and X. Chen): the role of monoamines in motor control has been a centre of attention since the discovery of the monoaminergic system. Up to date, however, only few classes of spinal interneurons have been examined in terms of motor function and their response to monoaminergic receptor activation. We combine these studies with another neuro-active protein, orexin that is linked strongly to motor control. The aim is the localization of receptors for orexin, it has been suggested that these systems may interplay to balance motor drive. The characterization of monoamine and orexin receptors in the lumbar spinal segments, the co-localization and the quantification of neurons with these receptors and the electrophysiological examination of the role orexin has on spinal interneuron populations is the main goal. This work relates to the characterization of spinal neural networks co-controlling respiratory, cardiac and locomotor output (supported by a one-year grant support from The Paul T. H. Thorlakson Foundation Fund, University of Manitoba). This work will utilize designer drugs exclusively activated by designer receptors delivered by the use of AAV-vectors and examine how activation of selected spinal neural clusters contributes to the simultaneous alteration of respiration, locomotion (fictive) and blood pressure changes in rats and mice.
- The role of connexin36 in the mature nervous system (in collaboration with J. Nagy): the family of connexin proteins have been linked to gap junction formation not only in the developing but also in the mature nervous system. Among twenty distinct connexins, it is well established that connexin36 (Cx36) is expressed in neurons and forms gap junctions that are the substrate of electrical synapses but their physiological relevance has only been inferred. In order to establish the functional role of electrical synapses in the neuronal circuitry of three relatively well-defined physiological systems, we performed pilot studies to establish the feasibility of examining the role of connexin specifically in the peripheral nervous system of mice in relation to the axon reflex. By the use of a Cx36 knock out mouse line, we propose to further investigate the physiological role of this protein (Nagy’s 2015 NSERC support). Both the peripheral and the central nervous system may utilize Cx36 and several different mechanisms can be involved, requiring several detailed functional studies in relation to the anatomical verification of the protein. One series of investigations is focusing on autonomic nerveous system output after spinal cord injury (supported by a one-year grant from the Manitoba Spinal Cord Injury Research Committee).
- Propriospinal networks contributing to locomotor activity generated in the lumbar spinal cord (in collaboration with B. Schmidt): the goal is to examine how a chain of neurons located in the thoraco-lumbar spinal cord contribute to the generation of locomotor activity. The pharmacological profiling of this network will be done in the mature rat to complement the decades of work on this system in the neonatal rat preparation (by B. Schmidt) and to better understand the development of locomotor control networks from neonatal to mature states.
- Human electrophysiology tests for the investigations of the role spinal neural networks in motor coordination: spinal networks allow the fastest left-right coordination during movement. They manifest as short reflex responses that are relatively easy to test clinically. How they can be used as therapeutic markers during rehabilitation of motor function after injury to the central nervous system such as stroke or spinal cord injury is yet unclear. The goals of these studies to utilize some of the known information about spinal networks in animal studies that have not yet been confirmed in humans or have not been explored in terms of motor control to establish basic clinical tests informative on left-right motor coordination. Alterations of other spinal neural function manifesting as facilitation or inhibition (in healthy and in spinal cord injured subject) is another unexplored field for its use in clinical tests. This work is partly conducted in collaboration with other researchers at the University of Manitoba but I am in the process of organizing a basic human electrophysiology laboratory, including surface electromyography recording set-ups, electrical simulators and a treadmill on which locomotor activity can be performed for future works on spinal networks and their control by the brain.
- Areas of Expertise
- Electrophysiology, brain, spinal cord, function network analysis, interneurons, sensory-motor coordination, reflex, surface EMGs, nerve stimulation, transcranial magnetic stimulation.
- Search PubMed for publications by Stecina K