Pathological dysfunctions that disrupt the circuitry of the prefrontal cortex and impair so-called “executive functions” and behavioral flexibility have been implicated in several psychiatric disorders and drug addiction. Current projects in the Kroener lab examine how drugs of abuse (specifically cocaine and alcohol) can alter the interaction of the PFC with other brain structures such as the amygdala or nucleus accumbens.
All of our projects use a combination of behavioral, electrophysiological, and immunohistochemical techniques. We also use many genetic tools, including viruses and transgenic animals, in order to characterize and manipulate specific neurons and connections.
Alcohol
We use various models of alcohol exposure (i.e., operant responding on various reinforcement schedules, or chronic intermittent ethanol exposure in vapor chambers) to study changes in glutamatergic synaptic transmission and NMDA receptor function in the PFC of mice. Chronic ethanol exposure induces homeostatic increases in NMDA receptors, which alters synaptic plasticity, contributing to a loss of response inhibition during the development and maintenance of addiction to alcohol.
Extinction Learning and VNS
A second line of work uses vagus nerve stimulation (VNS) as a tool to increase extinction from drug seeking and to prevent relapse. We currently explore how VNS-induced release of the brain-derived neurotrophic factor (BDNF) affects glutamatergic signaling and cell morphology in the PFC.
Mitochondrial Dysfunction in Schizophrenia
Our previous work in a murine developmental NMDA receptor-hypofunction model of schizophrenia indicated that the mitochondrial matrix protein Cyclophilin-D (CypD) regulates mitochondrial function and oxidative stress in PFC neurons. Using tissue from NIH’s NeuroBioBank we use immunohistochemical and molecular approaches in postmortem PFC tissue from patients with schizophrenia to determine if the disease correlates with abnormal levels of CypD.