Our brain’s ability to respond and adapt to stress is imperative to health, with dysfunctional neuroadaptation being a key trigger for development and exacerbation of a variety of neuropsychiatric disorders like depression, post-traumatic stress disorder (PTSD) and addiction. Endogenous cannabinoids (eCBs) are well established regulators of this stress response, making their sophisticated synaptic signaling mechanisms an area of great interest for neuroscientists. A major contributor to this body of knowledge on eCB biology in stress-related disorders has been Dr. Sachin Patel, Professor of Psychiatry and Molecular Physiology & Biophysics at Vanderbilt University in Nashville, Tennessee. His lab uses a range of cutting-edge circuit techniques including the Inscopix nVista miniscope, to probe deeper into the workings of the brain.
Imagine our excitement, then, when we got to speak with him about his lab, work and life. Thank you for taking your coffee break with us, Dr.Patel, we look forward to continue to support your important work!
What does your lab study?
We’re interested in understanding the mechanisms by which stress affects the brain to increase susceptibility to develop stress-related psychiatric disorders like PTSD and depression. Since I started my lab in 2010, we’ve been focused within this broader context on understanding how endocannabinoid systems are involved in stress responsivity and the synaptic & circuit level mechanisms by which they regulate it. Understanding this could facilitate advances in cannabinoid-based therapeutics for psychiatric disorders.
Does your lab have any favorite circuit neuroscience techniques at the moment?
We use a lot of electrophysiology! We like combining optogenetics, cell-type specific markers, and tracing approaches to define input-outfit pathways within the ex vivo slice preparation. This allows us to understand how distinct inputs/outputs interact with different cell populations, and how those interactions change in response to experience, different stress exposures or environmental manipulations.
We use mouse models for our experiments- genetic models where we can manipulate endocannabinoid signaling components within distinct cell types and circuits using viral approaches, conditional knockout approaches and behavioral paradigms like Pavlovian fear conditioning, extinction and exposure stress to model certain aspects of stress-related disorders.
What’s been your journey to becoming a circuit neuroscientist?
I did my undergrad at UC Santa Barbara in psychology, where my interest in neuroscience first began. Specifically, this was in neuroendocrinology and hypothalamic stress responses. Then I did my MD-PhD at the Medical College of Wisconsin in Milwaukee, where I first became interested in endocannabinoids’ role in regulation of stress responses and used behavioral, biochemical and analytical approaches to understand this. Finally, I came to Vanderbilt in 2006 for my Psychiatry residency, immediately after which I started my lab in 2010. During that time, I also did a postdoc with Danny Winder here at Vanderbilt, where I learned to incorporate ephys approaches to study eCB regulation of stress responsivity and adaptation at the synaptic, circuit level.
Even during my MD-PhD in training, I had always known I wanted to spend the majority of my time doing research. When I started my own lab, I focused our efforts on understanding particular neural pathways and circuits by which eCBs work, as well as the fundamental biology of how neural plasticity within defined circuits is regulated by experience or learning and memory in the form of, say, aversive Pavlovian conditioning. This has required that we incorporate novel techniques from time to time, such as ex vivo optogenetics and activity visualization using the Inscopix miniscopes, for example. Since we’ve now established the nVista system in our lab, there are several ongoing projects using it to look at population-level activity during different types of learning and memory, stress responses and even the effects of pharmacological treatment.
Visualization and signal extraction of prelimbic prefrontal cortical neurons with nVista 2.0 in freely moving mice
What are you currently most excited about in the eCB/stress disorders research area?
Most exciting to me are the inhibitors of eCB degradation that we and others have been examining preclinically, some for over a decade now. Certainly in my lab since the beginning, we’ve been interested in the potential therapeutic value of enhanced eCB signaling through inhibition of several degrading enzymes. We’ve been actively studying inhibitors of 2-AG metabolism, which are presently in Phase II clinical trials.
What advice do you have for early career neuroscientists?
I want to encourage them to take advantage of all the new approaches becoming available to answer the important and innovative questions that they may have. Let the question be your ultimate guide to selecting techniques, so you can approach it in the most sophisticated and in-depth way possible. Don’t be afraid of new technology! Lastly, be rigorous and thorough in your work and learn to be your own worst critic.
And finally, do you have any hobbies/interests outside the lab?
Apart from time with family and personal travels, I play the guitar. I always have for most of my life.
Thank you for stopping by!