Ryan Logan

Circadian rhythms are ~24-hour oscillations essential to nearly every biological process in the mammalian brain and body. Circadian rhythms are governed by a myriad of genetic (e.g.,gene variants) and environmental (e.g., light-dark cycles, mealtimes) factors. Alterations to these genetic and environmental factors can lead to circadian dysfunction. Disruption of circadian rhythms is strongly associated with a higher risk for psychiatric disorders, including mood and substance use disorders. Chronic stress and repeated substance use also have detrimental consequences on circadian rhythms, which likely contribute to psychiatric vulnerabilities. Despite these relationships, much of the current work linking psychiatric disorders to circadian dysfunction is correlational, with few causal, mechanistic findings of therapeutic value.

Our work focuses on the identification of mechanisms underlying the relationships between sleep, circadian rhythms, and mood (e.g., depression and bipolar) and substance use disorders. By integrating various approaches across humans and animals, we aim to discover the molecular, cellular, and neural circuit mechanisms that contribute to the development and progression of depression, bipolar, and substance use disorders. For example, we use postmortem brain tissue from humans to identify molecular and cellular pathways associated with opioid use disorder that we can further investigate in our animal models of opioid dependence. We are pursuing novel molecular targets identified in humans that regulate opioid reward, craving and relapse behaviors in mice. Notably, several of these proteins provide a molecular ‘bridge’ between sleep, circadian rhythms, and opioid dependence. In people with opioid use disorder, sleep and circadian disruptions are among the top complaint during abstinence and withdrawal and these disruptions are believed to be key drivers of craving and subsequent relapse to opioids. Given this, our research may provide viable biological targets for the development of novel, more effective treatments for opioid use disorder and other substance use disorders.

To investigate these mechanisms, we use a combination of approaches and techniques to cut across multiple biological scales – from genetics to molecular signaling pathways within specific cell-types connected among neural circuits that ultimately regulate complex behaviors that are related to psychiatric disorders. We use a variety of approaches, including functional genomics, transcriptomics, proteomics, and computational biology, along with in vivo viral-mediated gene manipulation, intersectional genetics and genome editing, and large-volume whole organ imaging. We aim to integrate these approaches to further understand the mechanisms of complex behaviors related to stress, anhedonia, reward, and motivation, at the intersection of sleep and circadian rhythms, and mood and substance use disorders.