Nicholas Canaday Spitzer

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 (Spitzer, 2017). We are also investigating neurotransmitter switching generated by environmental mouse models of autism spectrum disorders, depression and schizophrenia.