Lea Ziskind-Conhaim

Position title: Professor Emerita, Ph.D.

Email: lziskind@wisc.edu

Phone: (608) 263-3382

RESEARCH INTERESTS - Mechanisms of rhythm generation in locomotor-related interneurons in the mammalian spinal cord

Lea Ziskind-Conhaim

Spinal cord research Symposium (2012)

Spinal cord research Symposium (2009)

Photos from previous Spinal Cord Research Symposia:
2009   2007

Research in my laboratory focuses on identifying interneurons that are functional components of neural networks generating locomotor 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 elucidate the synaptic and intrinsic mechanisms by which the interneurons generate and coordinate locomotor rhythms in the mammalian spinal cord, and to determine their probable functions in the locomotor CPG, and 2) to examine the roles of spontaneous activity and sensory inputs on the assembly of the locomotor circuitry.

In our experiments, interneuronal populations of interest are identified in spinal cords of transgenic mice in which the genetically and functionally distinct interneurons express 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 determine the probable 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. The 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-filled interneurons, possible synaptic connections are identified. The properties of synaptic transmission between functionally identified interneurons are examined using paired intracellular recordings. Findings from these studies will increase our understanding of the cellular and synaptic mechanisms that regulate integrated rhythmic activity in distinct neuronal populations that comprise the CPG circuits in the mouse spinal cord.

Figure: Neurochemically induced locomotor-like voltage oscillations and rhythmic firing in neurobiotin-filled Hb9/GFP-expressing interneuron. ctivity, suggesting that the excitatory interneuron is a functional component of the rhythm-generating network.

Selected Publications

  • 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;240:129-34
  • 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
    Abstract | PDF
  • 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
    Abstract | PDF
  • Ziskind-Conhaim L. and Redman S.J. (2005). Spatiotemporal Patterns of Dorsal Root-Evoked Network Activity in the Neonatal Rat Spinal Cord: Optical and Intracellular Recordings. J Neurophysiol (May 11, 2005). doi:10.1152/jn.00209.2005.
    Abstract | PDF
  • Hinckley C A, Hartley, R, Wu, L, Todd, A and Ziskind-Conhaim, L (2005). Locomotor-Like Rhythms in a Genetically Distinct Cluster of Interneurons in the Mammalian Spinal Cord. J Neurophysiol 93: 1439-1449.
    Abstract | PDF
  • Hinckley CA, Seebach B, and Ziskind-Conhaim L (2005). Distinct roles of glycinergic and GABAergic inhibition in coordinating locomotor-like rhythms in the mouse spinal cord. Neurosci 131:745-758.
    Abstract | PDF
  • Lea Ziskind-Conhaim. Bao-Xi Gao, and Christopher Hinckley (2003). Ethanol dual modulatory actions on spontaneous postsynaptic currents in spinal motoneurons. J Neurophysiol 89:806-813.
    Abstract | Full Text | PDF
  • Rezan Demir, Bao-Xi Gao, Meyer B. Jackson, and Lea Ziskind-Conhaim (2002). Interactions Between Multiple Rhythm Generators Produce Complex Patterns of Oscillation in the Developing Rat Spinal Cord J Neurophysiol 87: 1094-1105.
    Abstract | Full Text | PDF
  • Gao, B-X, Stricker C and Ziskind-Conhaim, L (2001). Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks. J Neuorphysiol 86:492-502.
    Abstract | Full Text | PDF
  • Cheng, G, Gao, B-X, Verbny, Y and Ziskind-Conhaim, L (1999). Ethanol reduces neuronal excitability and excitatory synaptic transmission in the developing rat spinal cord. Brain Res 845:224-231.
  • Ziskind-Conhaim, L (1998). Physiological functions of GABA-induced depolarizations in the developing rat spinal cord. Perspectives on Dev Neurobiol 5: 279-287.
  • Gao, B-X and Ziskind-Conhaim, L (1998). Development of ionic currents underlying changes in action potential waveforms in rat spinal motoneurons. J Neurophysiol 80:3047-3061
    Abstract | Full Text
  • Gao, B-X, Cheng, G and Ziskind-Conhaim, L (1998). Development of spontaneous synaptic transmission in the rat spinal cord. J Neurophysiol 79: 2277-2287.
    Abstract | Full Text
  • Redmond, L, Xie, H, Ziskind-Conhaim, L and Hockfield, S. (1997). Cues intrinsic to the spinal cord determine the pattern and timing of primary afferent growth. Dev Biol 182:205-218.
    Abstract | Full Text
  • Xie, H and Ziskind-Conhaim, L (1995). Blocking Ca2+-dependent synaptic release delays motoneuron differentiation in the rat spinal cord. J Neurosci 15:5900-5911.