The primary goal of our research is 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.
Key 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.
- What is the ligand for dopamine receptors in V1, given that these receptors are found in all layers, but dopaminergic axons are only found in layers 1 and 6? If the ligand is not dopamine from the ventral tegmental area (VTA), this changes profoundly what dopamine signaling in V1 is likely ‘for’. If it *is* dopamine from the VTA, how does this molecule traverse the 1+mm from layer 1 or 6 to receptors in the middle layers of cortex on a time scale relevant for behavior?
- 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?
Other questions we are interested in include the ways that modulatory systems signal to each other to enable homeostatic control of state-specifying extracellular signals in cortex? And how does the extracellular space influence diffusion of modulators beyond synapses? How do gonadal hormones such as estrogen interact with modulatory systems? 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 a novel biosensor that combines classical electrophysiological recording capabilities with the ability to measure the local chemical environment at high spatial and temporal resolution; we also combine electrophysiological recording with pharmacological manipulation to examine causal relationships between neuromodulation, neuronal activity and behavioral performance. 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.