Northwestern University Feinberg School of Medicine

Ryan Drenan Lab

Opto-Pharmacology Approaches to Cholinergic Neurobiology

Pharmacology is a powerful discipline the seeks to understand how drugs and biologics interact withbiological systems such as receptors, cells, networks, and behaving animals. Optical techniques are useful in pharmacology, as light can often be harnessed and delivered to experimental system in ways that overcome certain challenges and allow new insights to be made.

In the Drenan lab, we are employing several advanced optical approaches in our studies of nicotinic acetylcholine receptor neurobiology. We use 2-photon laser scanning microscopy (2PLSM) to image important types of neurons that contribute to nicotine reward and withdrawal. Typically, this is done during simultaneous electrophysiological (patch clamp) recordings. The image at fdright shows a medial habenula neuron imaged via 2PLSM during patch clamp recording.

We also combine 2PLSM with “uncaging” approaches that allow us to precisely interrogate nicotinic receptor function in neurons, with subcellular resolution. We are gauncovering new details pertaining to cholinergic biology and nicotine addiction with these new tools and approaches. This graphic (at left) illustrates one version of this approach. In collaboration with Dr. Luke Lavis (JaneliaFarms HHMI), we are characterizing photoactivatable nicotine molecules during imaging/recording. These probes can be "uncaged" with 405 nm light from epi-illumination sources, or lasers.