UCSF

Neuromodulation encompasses a large array of mechanisms that regulate the excitability and dynamics of neuronal circuits. Activation of neuromodulatory receptors can regulate intrinsic neuronal excitability, synaptic transmission, activity-dependent neuroplasticity, homeostasis, gene transcription and other cell biological functions. These pathways are engaged both in healthy animals and during disease, and have been exploited by bioengineers to develop new experimental tools for controlling neuronal subpopulations in vivo. In this dissertation, we will describe several efforts to understand neuromodulation at multiple levels of analysis, from synapses to circuits. First, we will dissect the mechanisms underlying the regulation of vesicle release in prefrontal cortex by the neuromodulators dopamine and GABA. Then, we will develop an analytical pipeline for studying synaptic inputs in noisy electrophysiological recordings and apply this system to study how synapses are modulated by pathological conditions in a mouse model of autism. Finally, we validate a technique that allows for experimenter-controlled neuromodulation of genetically-identified cell populations and use it to study how the amygdala and hypothalamus regulate aggressive and mating behaviors in both sexes. Taken together, this dissertation sheds light on the physiological mechanisms, functional implications and technical applications of neuronal modulation in the mouse brain.