# Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $551,250

## Abstract

Project Summary Abstract:
Our perceptions, behaviors, emotions, memories and intelligence depend on the appropriate synthesis and
release of specific neurotransmitters in the brain. Transmitter identity is initially established by genetic
programs. It has been thought that transmitters are fixed and invariant throughout life and that the plasticity of
the nervous system consists largely of changes in the strength and number of synapses. We have found that
experimental perturbations of spontaneous electrical activity and natural changes in sustained sensory stimuli
such as ambient light or odors respecify transmitter identity in the spinal cord and brain in the developing
nervous system, leading to matching changes in postsynaptic transmitter receptor specification and changes in
animal behavior. Strikingly we found that transmitter switching and receptor matching also occur in the adult
mammalian brain in response to sustained sensory stimuli and can regulate behavior. These discoveries
contrast sharply with the general view of transmitter constancy and identify another way that the nervous
system adapts to the environment.
Here we describe experiments to determine how many transmitter switches are induced by a single
environmental stimulus and how many brain regions are affected. There is increasing understanding that the
brain is a widely linked network and that single perturbations alter activity throughout the brain. It is important
to address this issue in order to understand better the basis of changes in behavior in response to the
sustained stimuli that are major determinants of our conduct. A major part of our behavioral and cognitive
repertoire is habitual and results from sustained experience. We will also analyze the mechanisms that
promote and modulate transmitter switching. Although it is clear that neurotransmitter switching is activity-
dependent, the features of activity that are necessary to achieve switching remain unknown. In the future this
knowledge may have clinical utility for driving or preventing transmitter switching in patients.
The immediate goals of this research are to test specific hypotheses about the effect of activity in generating a
novel form of plasticity that involves changes in transmitter identity in the adult mammalian brain. The long-
term goals are to understand the role of neurotransmitter switching in regulating behaviors.

## Key facts

- **NIH application ID:** 9984794
- **Project number:** 1R35NS116810-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** NICHOLAS CANADAY SPITZER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $551,250
- **Award type:** 1
- **Project period:** 2020-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984794

## Citation

> US National Institutes of Health, RePORTER application 9984794, Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals (1R35NS116810-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984794. Licensed CC0.

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