The opioid crisis is a public health emergency. The rapid increase in overdose cases combined with the lack of effective therapeutics have necessitated a bold approach to combating this epidemic. Despite this new emphasis, opioids are still readily prescribed for chronic pain management and other conditions, introducing new addiction cases every day. If we could identify at-risk individuals before opioid exposure, it would significantly reduce the number of new opioid abusers.
Our lab aims to identify the neural substrates driving the maladaptive plasticity promoted by repetitive drug taking. We will map which brain circuits are modulated by drugs of abuse, how they are modulated, and how this pathological plasticity can be prevented and reversed through molecular or circuit-based interventions.
The brain is highly complicated. Our understanding of brain function is limited by the technologies we have to interrogate it. While the past two decades have seen rapid development and implementation of a wide variety of technologies, there are many questions we still cannot answer. For example, how does circuit activity change throughout the brain over time and expeirence? Current methods of monitoring neuronal activity are limited to one or a small number of brain sites, and we have limited control over the memories we form, both normal and pathological. Also, our decisions and actions are heavily influenced by the important but difficult to define “brain state”. What circuits and connections determine brain state? How does brain state modulate animal behavior?
Our lab is engineering novel viral-genetic and molecular methodologies to identify how neuronal circuit activity is modulated on a variety of timescales, and how activity in these circuits contributes to a variety of pathological states. We also are building a suite of molecular methodologies to control this plasticity on both local and global scales in an effort to reverse the maladaptive plasticity that drives a wide variety of pathological states.
While neural plasticity is crucial towards our ability to adapt to our environment, the same molecular and structural changes can be maladaptive and promote the development of neuropsychiatric conditions. This is true for a wide spectrum of disorders, including depression, anxiety, and PTSD, among others. Despite decades of research, very little progress has been made in curbing the mental health epidemic. New strategies are clearly needed to accelerate treatments to reduce the emotional and economic burden of these disorders.
Much of the high cost of treating neuropsychiatric conditions is due to their chronic nature. Current treatments can take months and even years to have any effect. A single-shot therapeutic would therefore have immense potential in revolutionizing treatments for a wide spectrum of diseases. As it is not clear for almost any neuropsychiatric disorder which brain sites and neuronal populations are driving particular symptoms, so identifying targets is a crucial first step towards this goal.
The most common neurological disorders, most of which are triggered by aging, cost the US over $800 billion annually. Normal and pathological aging promote cognitive and motor decline, symptoms that typically arise due to degeneration of specific neurons or circuits in the brain. These disorders include, but are not limited to, Alzheimer’s disease, Huntington disease, and Parkinson’s disease.
Using our viral-genetic strategies we aim to identify the neural circuit abnormalities that contribute to these disorders. Importantly, we will elucidate how these circuits are changed before the onset of pathology. These studies will both identify novel molecular and circuit targets for therapeutic development, as well as generate biomarkers for early clinical diagnosis of pathology.
