Mechanisms underlying rhythm generation in identified interneurons in the mammalian spinal cord.
Office Phone: (608) 263-3382, (608) 262-7820
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.
- Hinckley, C.A. and L. Ziskind-Conhaim. 2006. Electrical coupling between locomotor-related excitatory interneurons in the mammalian spinal cord. J. Neurosci. 26: 8477-8483.
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- Hinckley, C., B. Seebach and L. Ziskind-Conhaim. 2005. Distinct roles of glycinergic and GABAergic inhibition in coordinating locomotor-like rhythms in the mouse spinal cord. Neurosci. 131: 745-758.
- Ziskind-Conhaim, L., B-X. Gao, and C. Hinckley. 2003. Ethanol dual modulatory actions on spontaneous postsynaptic currents in spinal motoneurons. J. Neurophysiol. 89: 806-813.
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- Cheng, G., B-X. Gao, Y. Verbny, and L. Ziskind-Conhaim. 1999. Ethanol reduces neuronal excitability and excitatory synaptic transmission in the developing rat spinal cord. Brain Res. 845: 224-231.
- Gao, B-X, G. Cheng, and L. Ziskind-Conhaim. 1998. Development of spontaneous synaptic transmission in the rat spinal cord. J. Neurophysiol. 79: 2277-2287.
- Gao, B-X. and L. Ziskind-Conhaim. 1998. Development of ionic currents underlying changes in action potential waveforms in rat spinal motoneurons. J. Neurophysiol. 80: 3047-3061.
- Ziskind-Conhaim, L. 1998. Physiological functions of GABA-induced depolarizations in the developing rat spinal cord. Prospect. Dev. Neurobiol. 5: 279-287.
- Redmond, L., H. Xie, L. Ziskind-Conhaim, and S. Hockfield. 1997. Cues intrinsic to the spinal cord determine the pattern and timing of primary afferent growth. Dev. Biol. 182: 205-218.