Lynn Kirby, PhD
Professor, Anatomy and Cell Biology
Associate Professor, Center for Substance Abuse Research
- Contact Information
- About Me
Dr. Kirby’s research focuses on the effects of stress and stress hormones on the serotonin (5-HT) system. Serotonin is a brain neurotransmitter that is involved in a wide range of behaviors, including emotional behaviors. Long-term exposure to stress is known to play a role in psychiatric disorders such as anxiety and depression. Stress is also a potent initiator of relapse in abstinent subjects with a prior history of substance abuse. Some of these clinical effects of stress may in part be mediated by 5-HT. In the laboratory, we have examined the effects of stress and stress hormones on the electrical activity of 5-HT-containing cells in the brain and the release of 5-HT from nerve terminals. We have found that stress has qualitatively different effects on 5-HT neurotransmission depending on the brain region examined and the particular stressor that is employed. We have also examined the role of 5-HT in anxiety using a knockout mouse model in which a particular 5-HT receptor subtype (5-HT 1A) has been removed from the brain, resulting in an anxious behavioral phenotype. Previous studies also included investigation of the effects of chemokine immune molecules in the brain and their interactions with traditional neurotransmitter (5-HT, dopamine) and neuropeptide (opiate) systems. Currently, we are examining the potential role that 5-HT circuits play in opiate and cocaine addiction and relapse. Through collaborations with other laboratories we are also exploring cannabinoid effects on cognition, synaptic plasticity and inflammation produced in a model of stroke.
Dr. Kirby’s laboratory uses a combination of behavioral, neurochemical, electrophysiological and anatomical techniques in rodents. We employ both in vivo extracellular single-unit recording and in vitro whole cell recording techniques in a brain slice preparation to examine the effects of stress and the stress neurohormone corticotropin-releasing factor (CRF) on neuronal activity in the serotonergic dorsal raphe nucleus (DRN). We also conduct field recordings in hippocampal brain slices to examine drug effects on long-term synaptic plasticity. In addition, we have used in vivo microdialysis techniques to examine stress effects on 5-HT release in target sites. We use immunohistochemical and tract-tracing methods to examine the neural circuits whereby stress and stress hormones modulate the 5-HT system. To experimentally induce stress, we frequently employ the forced swimming test: a behavioral screen for antidepressant efficacy that potently activates the hypothalamopituitary-adrenal axis as well as producing biphasic, region-specific changes in 5-HT neurotransmission. Current studies testing the role of the serotonergic DRN in opiate and cocaine addiction and relapse also employ behavioral as well as electrophysiological measures. Opiate modulation of 5-HT DRN neurons and their synaptic afferents are compared to the effects of CRF in vitro. The role of these DRN circuits in stress-induced opiate relapse are examined using a behavioral model in which swim stress is used to induce reinstatement of previously extinguished morphine conditioned place preference or cocaine self-administration. We are now in the process of generating transgenic mice with conditional deletion of GABA genes in the DRN or in 5-HT neurons. We are testing the hypothesis that lack of GABAergic inhibition of the 5-HT DRN system will produce resistance to stress-induced opioid or cocaine reinstatement in our behavioral models. All of these studies integrate electrophysiological, neurochemical, anatomical and behavioral techniques in order to elucidate the neurobiological substrates of depression, anxiety and substance abuse with a long-term goal of identifying novel targets for their treatment.
- Education, Training & Credentials
- Postdoctoral Fellowship, Children’s Hospital of Philadelphia, Philadelphia, PA
- Postdoctoral Fellowship, MCP Hahnemann University, Philadelphia, PA
- PhD, Neuroscience, University of Pennsylvania, Philadelphia, PA, 1997
- BA, Psychobiology, Swarthmore College, Swarthmore, PA