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Nicholas C. Spitzer

Research

The brain is capable of a rich variety of forms of plasticity, changing its structure and function in response to changes in the environment. We study neurotransmitter switching, a newly appreciated form of neuroplasticity in which neurons change the transmitters that they make and release in response to sustained sensory or motor activity. Transmitter identity shifts from excitatory to inhibitory or vice versa, with matching changes in postsynaptic receptors, both in the developing amphibian nervous system and in the adult rodent brain. Perhaps unsurprisingly the reversal of the sign of synaptic transmission is accompanied by changes in the animals’ behavior.

Our work is focused on understanding the cues that stimulate neurotransmitter switching in the developing and adult mouse brain, the prevalence and forms of this plasticity, and its functions. We want to learn the molecular mechanisms that regulate neurotransmitter switching and the mechanisms by which the appropriate, matching transmitter receptors are expressed on postsynaptic cells. We are investigating neurotransmitter switching in response to normal physiological stimuli and to aversive stimuli such as stress that lead to neurological disorders like depression and schizophrenia.

Our recent studies have demonstrated the roles of sensory stimuli and direct manipulations of activity in neurotransmitter switching in the developing Xenopus hypothalamus, brainstem, and accessory olfactory bulb (Dulcis & Spitzer, 2008; Demarque & Spitzer, 2010; Dulcis et al., in review) and in the adult rat hypothalamus (Dulcis et al. 2013) that change specific behaviors. Ongoing projects address the role of motor activity in neurotransmitter switching in the adult mouse midbrain and hippocampus that may regulate procedural learning and neurogenesis. We are also investigating neurotransmitter switching generated by environmental mouse models of autism spectrum disorders.

Publications

  • Spitzer, N.C. (2015) Neurotransmitter switching? No surprise. Neuron 86: 1131-1144.
  • Güemez-Gamboa, A. Xu, L., Meng, D., Spitzer, N.C. (2014) Non-cell-autonomous mechanism of activity-dependent neurotransmitter switching. Neuron 82: 1004-1016.
  • Dulcis, D., Jamshidi, P., Leutgeb, S. and Spitzer, N.C. (2013) Neurotransmitter switching in the adult brain regulates behavior. Science 340: 449-453.
  • Plazas, P.V., Nicol, X. and Spitzer, N.C. (2013) Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3. Proc. Nat. Acad. Sci. USA. 110: 1524-1529.
  • Spitzer, N.C. (2012) Activity-dependent neurotransmitter respecification. Nature Reviews Neurosci. 13: 94-106.
  • Dulcis, D. and Spitzer, N.C. (2012) Reserve pool neuron transmitter respecification: novel neuroplasticity. Dev. Neurobiol. 72: 465-474.
  • Demarque, M. and Spitzer, N.C. (2012) Neurotransmitter phenotype plasticity: an unexpected mechanism in the toolbox of network activity homeostasis. Dev. Neurobiol. 72: 22-32.
  • Nicol, X., Hong, K.P. and Spitzer, N.C. (2011) Spatial and temporal second messenger codes for growth cone turning. Proc. Nat. Acad. Sci. USA. 108: 13776-13781.
  • Velázquez-Ulloa, N.A., Spitzer, N.C. and Dulcis, D. (2011) Context-dependent dopamine specification by calcium activity across the central nervous system. J. Neurosci. 31: 78-88.
  • Demarque, M. and Spitzer, N.C. (2010) Activity-dependent expression of Lmx1b regulates specification of serotonergic neurons modulating swimming behavior. Neuron 67: 321-334.
  • Marek, K.W., Kurtz, L.M. and Spitzer, N.C. (2010) cJun integrates calcium spike activity and tlx3 expression to regulate neurotransmitter specification. Nature Neurosci. 13: 944-950.
  • Xiao, Q., Xu, L. and Spitzer, N.C. (2010) Muscle-dependent regulation of neurotransmitter specification and embryonic neuronal calcium spike activity. J. Neurosci. 30: 5792-5801.
  • Chang, L.W. and Spitzer, N.C. (2009) Spontaneous calcium spike activity in embryonic spinal neurons is regulated by developmental expression of the Na+, K+-ATPase β3 subunit. J. Neurosci. 29: 7877-7885.
  • Dulcis, D. and Spitzer, N.C. (2008) Illumination controls dopaminergic differentiation regulating behavior. Nature 456: 195-201.
  • Root, C.M., Velazquez-Ulloa, N.A., Monsalve, G.C., Minakova, E. and Spitzer, N.C. (2008). Embryonically expressed GABA and glutamate drive electrical activity regulating neurotransmitter specification. J. Neurosci. 28: 4777-4784.
  • Sann, S.B., Xu, L., Nishimune, H., Sanes, J.R. and Spitzer, N.C. (2008). Neurite outgrowth and in vivo sensory innervation mediated by a CaV2.2-laminin beta-2 stop signal. J. Neurosci. 28: 2366-2374.
  • Borodinsky, L.N. and Spitzer, N.C. (2007). Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction. Proc. Natl. Acad. Sci. 104: 335-340.
  • Spitzer, N.C. (2006). Electrical activity in early neuronal development. Nature 444: 707-712.
  • Conklin, M.W., Lin, M.S. and Spitzer, N.C. (2005). Local calcium transients contribute to disappearance of pFAK, focal complex removal and deadhesion of neuronal growth cones and fibroblasts. Dev. Biol. 287: 201-212.
  • Borodinsky, L.N., Root, C.M., Cronin, J.A., Sann, S.B., Gu, X. and Spitzer, N.C. (2004). Actiity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429: 523-530.
  • Gorbunova, Y.V. and Spitzer, N.C. (2002). Dynamic interactions of cAMP transients and spontaneous calcium spikes. Nature 418: 93-96.
  • Gomez, T.M., Robles, E., Poo, M. and Spitzer, N.C. (2001). Filipodial calcium transients promote substrate-dependent growth cone turning. Science 291: 1983-1987.

Biography

Nick Spitzer received his Ph.D. from Harvard University and was a postdoctoral fellow at Harvard and University College, London. He joined the faculty in 1972 and has been the recipient of a Sloan Fellowship, a Javits Neuroscience Investigator Award and a Guggenheim Fellowship. He was founding editor-in-chief of BrainFacts.org, and is a fellow of the American Association for the Advancement of Science, a member of the American Academy of Arts and Sciences and the National Academy of Sciences and co-director of the Kavli Institute for Brain and Mind.