Welcome to the Plotkin Lab-
At any given moment, our brain is confronted with the formidable task of sorting through a slew of possible actions that can be performed. Some of these actions are beneficial and should be green lit. Some are inappropriate and must be suppressed. The inability to properly do this is at the crux of many neurological disorders- perhaps most notably obsessive compulsive disorder (OCD).
The brain region that is most intimately associated with this type of "action selection" is called the basal ganglia, a collection of nuclei located under the cerebral cortex. It has the daunting task of receiving large amounts of information from diverse regions of the brain and, based on what has worked in the past and what has not, making a recommendation about which tasks should be performed and which should not.
Despite the central role the basal ganglia plays in action selection and habit learning, a major obstacle has limited our understanding of how it functions. This obstacle is the anatomy of the basal ganglia itself. The portion of the basal ganglia that receives nearly all of the inputs from other parts of the brain (known as the "striatum") is made up of many different types of intermingled neurons- the vast majority of these neurons look identical under a traditional light microscope, but respond to neuromodulators differently and have opposing effects on basal ganglia output. Furthermore, each of these types of neurons receives thousands of synaptic inputs encoding different information- but these inputs overlap, making it challenging to tease apart how a striatal neuron receives and integrates information from specific origins.
Our lab is using cutting edge optical imaging techniques to overcome this obstacle. Using a combination of 2-photon laser scanning microscopy, electrophysiology, localized delivery of neurotransmitters with laser-induced photolysis, optogenetics, surgical manipulations and transgenic mice, we are beginning to dissect the functional microcircuitry of the basal ganglia at a level that was previously not possible. We are exploiting this technology to interrogate the physiological underpinnings of action selection and habit learning, and how basal ganglia circuitry and function are altered in mouse models of obsessive compulsive disorder.