Research

Our group’s overall research goals are centered on elucidating the neurobiological mechanisms underlying motivated behaviors and behavioral deficits associated with neuropsychiatric disorders, such as depression. At present, we are focused on determining how drugs of abuse modulate brain circuitries involved in the emergence and maintenance of drug seeking behaviors that characterize addiction. While the vast majority of research in the field has focused on the mesocorticolimbic dopamine ‘reward’ pathway, much less is known about the involvement of other motivation-related circuits in addiction. Further, given the high comorbidity between depression and substance abuse, it has been proposed that similar mechanisms may mediate both disease states, and/or individuals with depression may consume drugs of abuse to modulate symptoms associated with the disorder. 

Recently, we established a key role for the medial habenula (MHb) and its major afferent target, the interpeduncular nucleus (IPN), in controlling the addictive properties of nicotine. Specifically, we found that nicotinic acetylcholine receptors (nAChRs) in the MHb-IPN, particularly those containing α5 subunits, control the aversive effects of nicotine and thereby limit consumption of the drug. This finding likely explains why human allelic variation in the gene encoding the α5 subunit gene (CHRNA5) dramatically increases vulnerability to tobacco dependence and smoking related diseases in humans, such as lung cancer. Moreover, these data have promoted the pharmaceutical development of novel small molecule α5 nAChR ligands that will potentially be used as smoking cessation agents. 

Currently, my laboratory is focused on defining the epigenetic and neurobiological mechanisms mediating gene expression in the habenula-IPN circuitry and its downstream targets. One line of research focuses on defining the influence of extracellular-derived RNAs on neuronal function and the subsequent effect on behaviors underlying addiction and depression. Our second line of research utilizes DREADD and optogenetic approaches to define the circuits downstream from the habenula-IPN pathway for their involvement in nicotine reinforcement, reinstatement, and withdrawal.