We take a multidisciplinary approach to study the neurobiology of motivation using tools spanningsystems, molecular, cellular, & behavioral neuroscience.
Intersectional genetics
We use viral and intersectional genetic methods to restrict expression of reporters and effector molecules to anatomically and genetically defined neuronal populations. These methods allow us to uncover the diverse roles of specific cell types in motivated behavior.
In vivo recordings using genetically encoded calcium indicators (e.g., GCaMP) or neurotransmitter sensors (e.g., norepinephrine sensor) allow us to measure the activity patterns of defined neuronal populations in behaving mice. By leveraging a custom-built system that uses two spectrometers, we are able to simultaneously monitor fluorescent activity in up to two brain regions. Our lab uses this fiber photometry system to understand how temporally-specific changes in neuronal activity is involved in encoding appetitive and consummatory behavior.
We are performing single-cell, single-photon imaging of calcium and neurotransmitter activity with fluorescence based sensors (e.g., GCaMP, GRAB-NE sensor) recorded using implantable miniature microscopes in freely behaving mice. The Inscopix nVue system enables dual color imaging of two distinct cell populations, whereas the nVoke system enables single color imaging with simultaneous optogenetic manipulation to causally link neural circuit activity with behavior. We are applying these technologies to determine the neuromodulatory effects of locus coeruleus activity on forebrain neurons regulating feeding and taste.
Optogenetics
Optogenetic technologies allow us to manipulate neuronal activity in precise cells and circuits with high-temporal resolution. The optogenetic toolbox includes different types of ion gated channels, including channelrhodopsin and halorhodopsin, that are activated by blue and yellow light respectively and rapidly lead to bidirectional changes in neuronal activity. We use wired and wireless optogenetic technologies that couple light- and drug-delivery in the same device, providing an ability to manipulate neuronal activity on fast and longer timescales.
We leverage chemogenetics to non-invasively control activity of diverse cell types to uncover their function in motivational processes. This technique uses Designer Receptors Exclusively Activated by Designer Drugs (DREADDS), which are G-protein coupled receptors that have been mutated in such a way that they are no longer responsive to the innate ligand acetylcholine, but instead are activated by designer drugs. We deliver these drugs peripherally or directly into the brain to understand the function of different brain cell types and their signaling processes in motivated behavior.
Electrophysiological recordings allow us to examine changes in synaptic and firing activities of neurons that play an important role in consummatory processes. We combine electrophysiological recordings with optogenetic and chemogenetic manipulation methods, to provide insight into neural circuit function. We perform different variations of the patch clamp technique, including cell-attached and whole cell-patch recordings to study electrical behavior of individual ion channels and the entire neuron.
We use in vivo microdialysis to quantify neurotransmitters, including the catecholamines norepinephrine (NE) and dopamine (DA), as well as their metabolites, in discrete brain regions during behavior. In vivo microdialysis uses a probe to sample extracellular fluid from the brain, and can be used in combination with many other techniques in the lab to understand how neurotransmitter release is related to variations in neural activity and behavior.
We use a variety of histological techniques, including immunohistochemistry for protein labeling and fluorescent in situ hybridization for mRNA labeling in mouse brain tissues. We then visualize our samples using confocal and epifluorescence microscopy.
Our work focuses on motivated behaviors which have distinct phases. The appetitive phase is directed towards seeking a desired stimulus (e.g., Seeking food or drugs of abuse), and the consummatory phase includes sensory, motor and reward processes related to obtaining the desired outcome (e.g., eating food, self-administering drugs). We also study aversion, another motivated behavior, characterized by agitation and defense due to the presence of a stressor (e.g. predator). By monitoring behavior at high temporal resolution using state-of-the art tracking systems (e.g., DeepLabCut, Noldus Ethovision), we are able to link changes in behavior to neural activity.
