There are two broad branches of research in our lab:
The main thrust of our lab’s work is our Discovery Science Program which aims to determine the role(s) that neuromodulators such as acetylcholine, noradrenaline, serotonin, and oxytocin play in specifying functional connectivity across the wired circuitry of the brain, and how this dynamic circuit specification supports flexible behavior in the healthy brain. In this work, we use methods from neuroanatomy, neurophysiology and pharmacology, and neurochemistry. We are particularly interested in thinking about these problems in terms of Complex Systems Theory, and Adaptive Control Theory.
We also have a small Disease-Focused Research Program that aims to understand neurochemical changes that occur across the menopause transition and in the pre-clinical phase (i.e 20-30 years before symptom onset and diagnosis) of late-onset (or spontaneous) Alzheimer’s Disease. Late onset AD accounts for >95% of the disease burden for AD but because it is not genetically determined and so is not well-modeled by the transgenic mice commonly used in AD research, it is far less well understood than familial AD.
Key Discovery Science questions we are working on in the lab at the moment include:
- When and how do acetylcholine and serotonin determine which information makes it into the primary visual cortex (V1) from the thalamus? This is a critical question because you’re very limited in the ways that you can make decisions based on visual information that does not make it into the cortex.
- Which neuromodulators modulate feedback into V1 from higher visual areas? What form does the modulation take? (How) Does modulation of feedback modify V1 receptive fields?
- Over what spatial and temporal scale is acetylcholine released into V4 during a visual attention task? And how does this relate to attention-related changes in spiking activity?
- How to neural networks read out and integrate the information carried in neuromodulatory signals?
Other questions we are interested in include the ways that modulatory systems signal to each other in cortex? How does the extracellular space influence diffusion of modulators beyond synapses? How do networks learn to properly self-modulate? What happens to neuromodulatory signaling as we age?
We are a question-driven lab, and so the techniques we employ are diverse. Where the technique we need in order to answer our question doesn’t exist, we work to develop it.
Our current tools include psychophysics and behvaioral analysis, electrophysiological and electrochemical recording combined with pharmacological manipulation and task-based behavioral control to examine causal relationships between neuromodulation, neuronal activity and behavioral performance. Our current analysis methods include the tools of analytic chemistry, including mass spectrometry-based proteomics and metabolomics. Because we believe that structure constrains function, we anchor all of our research in a solid understanding of cortical anatomy. Where these data don’t exist, we generate them which means we also study the anatomy of neuromodulatory systems in cortex from a comparative perspective at both the light and electron microscopic levels.
