2. Modulatory glutamate signaling: impact on motor function, novelty, and cocaine addiction

Glutamate is the major excitatory neurotransmitter in the brain, but also has a modulatory role by signaling through metabotropic glutamate receptors (mGluRs). Recent work from our laboratory revealed that mGluR5 expression in DA neurons is required for DA signaling and several DA-dependent behaviors including motor learning and cocaine reward. However, the circuit- and mechanistic-specific underpinnings of these processes are unkonwn. Using a novel conditional knockout model, we are leveraging genetically encoded DA sensors to determine how DAergic mGluR5 impacts DA neuron function and DA-dependent behaviors in mice. Rotation students will learn to behaviorally assess cocaine addiction in this mouse model, and will learn immunohistochemical approaches to validate viral expression

Cocaine Fails to increase DA in mGluR5-DA-silenced mice. Fiber photometry using genetically-encoded DA sensors during cocaine response. Control or mGluR5-DA-silenced mice were injected with 7.5 mg/kg cocaine and DA signals were recorded in the nucleus accumbens using dLight 1.2 sensor. Control mice: Cocaine caused a significant increase in the total DA signal from 3-5 min post-injection as compared to saline-injections. mGluR5-DA-silenced mice: Cocaine failed to significantly increase DA signals. *p<0.05, paired Student's t test, n=4-5.