One thing that I think is cool about the brain is that it’s the only organ that studies itself. The brain operates through a series of complex networks composed of neurons. The neurons transmit signals by sending electrical impulses to one another and releasing neurotransmitters. Neurotransmitters are chemical proteins that bind to receptors to activate the systems responsible for our perception, behavior, and other bodily functions. Different parts of the brain are connected by these circuits, and although we’ve learned a lot about how neural circuits work, there’s still much that remains unknown.
This summer, I’ll be working to better understand the role of specific types of neurons (parvalbumin-expressing (PV) interneurons) in the neural circuits of a specific part of the brain (primary visual cortex (V1)). We’re using a technique called Drugs Acutely Restricted Tethering (DART) to manipulate the activity of PV interneurons. DART works by using a “buddy system” where the drug we’re using is paired with a DART protein. The two proteins are linked together so that, when DART binds to a receptor, the drug is subsequently confined and can only bind to nearby receptors. The type of receptor we’re studying is found all throughout the brain, so using this technique allows us to be more specific in what area of the brain we’re treating and minimize off-target effects.
However, in order for this technique to work, the DART protein needs a specific receptor to bind to that is only expressed in the areas where we want DART to bind. Thus, we are first injecting a virus that will facilitate the expression of the HaloTag receptor on the surface of PV interneurons. Ultimately, HaloTag will serve as an anchor for DART which is connected to a drug that will in-turn be confined so that it can only bind to certain receptors so that we can manipulate the overall activity of the cells. This will not only give us a better understanding of the role of PV interneurons in neural circuits but also validate the use of a new technique for interneuronal manipulation that could aid in the development of clinical therapies for neurological disorders.