- Professor, Department of Neuroscience
- (608) 263-3382
Ph.D. The Hebrew University, Israel
Mechanisms Underlying Rhythmic Generation in Identified Interneurons in the Mammalian Spinal Cord
Research in my laboratory focuses on identifying interneurons that are functional components of neural networks generating locomotor-like rhythms in the mammalian spinal cord. Locomotion in vertebrates is produced by autonomous spinal circuits, central pattern generators (CPGs) that are responsible for movements and can function independently of descending and peripheral inputs. The long-term goals of our studies are: 1) to examine the electrophysiological and morphological properties of subpopulations of locomotor-related excitatory and inhibitory interneurons, and to determine their probable functions in the locomotor CPG, and 2) to elucidate the synaptic and intrinsic mechanisms by which the interneurons generate and coordinate locomotor-like rhythms in the mammalian spinal cord.
Progress in identifying interneurons that are functionally integrated component of the CPG has been slow, partly because determining synaptic circuitry requires the classification of particular neuronal populations. To overcome some of the technical limitations of interneuron identification in the isolated spinal cord, transgenic mice have been used with the intention of characterizing interneurons with genetic markers. An innovative approach has recently become available with the discovery that subpopulations of ventral interneurons can be distinguished by combinatorial expression of transcription factors. To visualize genetically distinct interneuronal populations, transcription factors are used to control the expression of the reporter gene green fluorescent protein (GFP). GFP expression in specific excitatory and inhibitory interneurons allows us to visually target them for electrophysiological, morphological and immunohistochemical studies. To characterize the role of GFP-expressing interneuronal populations in the locomotor CPG, whole-cell patch clamp recordings are performed to correlate their electrical activity with induced locomotor-like rhythmic motor outputs. Those interneurons are labeled with the intracellular marker neurobiotin to further study their morphological and immunohistochemical characteristics. Based on the pattern of dendritic arborization and axonal projections of neurobiotin-labeled interneurons, possible synaptic connections are identified. The properties of synaptic transmission between functionally identified interneurons are examined using paired intracellular recordings and real-time images of fast voltage-sensitive dyes. Findings from these studies will increase our understanding of the cellular and synaptic mechanisms that underlie integrated rhythmic activity in distinct neuronal populations that constitute the CPG networks.
- Ziskind-Conhaim L.(2013)Neuronal correlates of the dominant role of GABAergic transmission in the developing mouse locomotor circuitry. Ann N Y Acad Sci 2013 Mar;1279:43-53
- Mavlyutov TA, Epstein ML, Verbny YI, Huerta MS, Zaitoun I, Ziskind-Conhaim L, Ruoho AE. (2012) Lack of sigma-1 receptor exacerbates ALS progression in mice. Neuroscience 2013 Jun 14;240:129-3
- Mavlyutov TA, Epstein ML, Liu P, Verbny YI, Ziskind-Conhaim L, Ruoho AE. (2012) Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N,N'-dimethyltryptamine forming enzyme, indole-N-methyl transferase. Neuroscience 2012 Mar 29;206:60-8
- Wu, L, Sonner, PM, Titus, DJ, Wiesner, EP, Alvarez, FJ and Ziskind-Conhaim, L (2011). Properties of a distinct subpopulation of GABAergic commissural interneurons that are part of the locomotor circuitry in the neonatal spinal cord. J Neurosci 31:4821-4833
- Hinckley, CA, Wiesner, EP, Mentis, GZ, Titus DJ and Ziskind-Conhaim, L (2010).Sensory modulation of locomotor-like membrane oscillations in Hb9-expressing interneurons. J Neurophysiol 103:3407-3423
- Ziskind-Conhaim, L, Mentis, GZ, Wiesner, EP and Titus, DJ (2010). Synaptic integration of rhythmogenic neurons in the locomotor circuitry: the case of Hb9 interneurons. Ann N Y Acad Sci 1198: 72-84
- Mavlyutov TA, Epstein ML, Andersen KA, Ziskind-Conhaim L and Ruoho AE (2010). The sigma-1 receptor is enriched in postsynaptic sites of C-terminals in mouse motoneurons. An anatomical and behavioral study. Neurosci 167: 247-55
- Ziskind-Conhaim L, Wu L, Wiesner EP (2008). Persistent sodium current contributes to induced voltage oscillations in locomotor-related Hb9 interneurons in the mouse spinal cord. J Neurophysiol 100: 2254-2264
- Ziskind-Conhaim L, Hinckley CA (2008). Hb9 versus type 2 interneurons. J Neurophysiol 99: 1044-1046
- Hinckley C. and Ziskind-Conhaim L. (2006). Electrical Coupling between Locomotor-Related Excitatory Interneurons in the Mammalian Spinal Cord. J Neurosci August 16, 2006, 26(33):8477-8483; doi:10.1523/JNEUROSCI.0395-06.2006