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Lynn Kirby , PhD

Associate Professor, Anatomy and Cell Biology

Telephone:  215-707- 8556

Fax:  215-707-9468

Email: lkirby@temple.edu

Department of Anatomy and Cell Biology

Center for Substance Abuse Research

Swarthmore College, Swarthmore, PA
B.A., Psychobiology

University of Pennsylvania, Philadelphia , PA
Ph.D., 1997, Neuroscience
Advisor: Irwin Lucki, Ph.D.

MCP Hahnemann University, Philadelphia, PA
Postdoctoral Fellowship
(Sponsor: Rita J. Valentino, Ph.D.)

Children’s Hosp. of Philadelphia, Philadelphia, PA
Postdoctoral Fellowship
(Sponsor: Sheryl G. Beck , Ph.D.)

 

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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. One current project is an investigation of the effects of chemokine immune molecules in the brain and their interactions with traditional neurotransmitter (5-HT, dopamine) and neuropeptide (opiate) systems. In another current project, we are examining the potential role that 5-HT circuits play in opiate addiction and relapse.

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). 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. In the chemokine project, interactions between chemokines and neurotransmitter or neuropeptide systems are examined with a combination of anatomical and electrophysiological techniques. Future work will examine the impact of chemokines on the 5-HT system in vivo including their effects on 5-HT-related behavior. Current studies testing the role of the serotonergic DRN in opiate 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. 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.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

23812764. Li C, Staub DR, Kirby LG, Role of GABA_A receptors in dorsal raphe nucleus in stress-induced reinstatement of morphine-conditioned place preference in rats. Psychopharmacology (Berl) :()2013 Jun 28

23478745. Giannopoulos PF, Chu J, Joshi YB, Sperow M, Li JG, Kirby LG, Praticò D, Gene knockout of 5-lipoxygenase rescues synaptic dysfunction and improves memory in the triple-transgenic model of Alzheimer's disease. Mol Psychiatry :()2013 Mar 12

22047957. Staub DR, Lunden JW, Cathel AM, Dolben EL, Kirby LG, Morphine history sensitizes postsynaptic GABA receptors on dorsal raphe serotonin neurons in a stress-induced relapse model in rats. Psychoneuroendocrinology 37:6(859-70)2012 Jun

21569838. Chen X, Kirby LG, Palma J, Benamar K, Geller EB, Eisenstein TK, Adler MW, The effect of gp120 on morphine's antinociceptive and neurophysiological actions. Brain Behav Immun 25:7(1434-43)2011 Oct

21466815. Kirby LG, Zeeb FD, Winstanley CA, Contributions of serotonin in addiction vulnerability. Neuropharmacology 61:3(421-32)2011 Sep

21402095. Schneider AM, Simson PE, Atapattu RK, Kirby LG, Stress-dependent impairment of passive-avoidance memory by propranolol or naloxone. Pharmacol Biochem Behav 98:4(539-43)2011 Jun

21160465. Lemos JC, Zhang G, Walsh T, Kirby LG, Akanwa A, Brooks-Kayal A, Beck SG, Stress-hyperresponsive WKY rats demonstrate depressed dorsal raphe neuronal excitability and dysregulated CRF-mediated responses. Neuropsychopharmacology 36:4(721-34)2011 Mar

20981413. Freeman-Daniels E, Beck SG, Kirby LG, Cellular correlates of anxiety in CA1 hippocampal pyramidal cells of 5-HT1A receptor knockout mice. Psychopharmacology (Berl) 213:2-3(453-63)2011 Feb

20974247. Heinisch S, Palma J, Kirby LG, Interactions between chemokine and mu-opioid receptors: anatomical findings and electrophysiological studies in the rat periaqueductal grey. Brain Behav Immun 25:2(360-72)2011 Feb

20363293. Huang P, Liu-Chen LY, Kirby LG, Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze. Neurosci Lett 475:3(165-8)2010 May 21

19755127. Heinisch S, Kirby LG, SDF-1alpha/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus. Neuropharmacology 58:2(501-14)2010 Feb

19748551. Heinisch S, Kirby LG, Fractalkine/CX3CL1 enhances GABA synaptic activity at serotonin neurons in the rat dorsal raphe nucleus. Neuroscience 164:3(1210-23)2009 Dec 15

19523491. Schneider AM, Simson PE, Spiller K, Adelstein J, Vacharat A, Short KR, Kirby LG, Stress-dependent enhancement and impairment of retention by naloxone: evidence for an endogenous opioid-based modulatory system protective of memory. Behav Brain Res 205:1(290-3)2009 Dec 14

19036986. Kirby LG, Freeman-Daniels E, Lemos JC, Nunan JD, Lamy C, Akanwa A, Beck SG, Corticotropin-releasing factor increases GABA synaptic activity and induces inward current in 5-hydroxytryptamine dorsal raphe neurons. J Neurosci 28:48(12927-37)2008 Nov 26

17602840. Kirby LG, Pan YZ, Freeman-Daniels E, Rani S, Nunan JD, Akanwa A, Beck SG, Cellular effects of swim stress in the dorsal raphe nucleus. Psychoneuroendocrinology 32:6(712-23)2007 Jul

14573555. Beck SG, Pan YZ, Akanwa AC, Kirby LG, Median and dorsal raphe neurons are not electrophysiologically identical. J Neurophysiol 91:2(994-1005)2004 Feb

12573710. Kirby LG, Pernar L, Valentino RJ, Beck SG, Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies. Neuroscience 116:3(669-83)2003

12172694. Price ML, Kirby LG, Valentino RJ, Lucki I, Evidence for corticotropin-releasing factor regulation of serotonin in the lateral septum during acute swim stress: adaptation produced by repeated swimming. Psychopharmacology (Berl) 162:4(406-14)2002 Aug

11919622. Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, Kirby L, Santarelli L, Beck S, Hen R, Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416:6879(396-400)2002 Mar 28

10649828. Kirby LG, Rice KC, Valentino RJ, Effects of corticotropin-releasing factor on neuronal activity in the serotonergic dorsal raphe nucleus. Neuropsychopharmacology 22:2(148-62)2000 Feb

10591883. Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I, Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology (Berl) 147:2(162-7)1999 Nov

9876256. Kirby LG, Lucki I, The effect of repeated exposure to forced swimming on extracellular levels of 5-hydroxytryptamine in the rat. Stress 2:4(251-63)1998 Dec

9571657. Price ML, Curtis AL, Kirby LG, Valentino RJ, Lucki I, Effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology 18:6(492-502)1998 Jun

9262365. Kirby LG, Lucki I, Interaction between the forced swimming test and fluoxetine treatment on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the rat. J Pharmacol Exp Ther 282:2(967-76)1997 Aug

9237538. Kirby LG, Chou-Green JM, Davis K, Lucki I, The effects of different stressors on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 760:1-2(218-30)1997 Jun 20

7552310. Kirby LG, Allen AR, Lucki I, Regional differences in the effects of forced swimming on extracellular levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 682:1-2(189-96)1995 Jun 5

7570349. Kirby LG, Kreiss DS, Singh A, Lucki I, Effect of destruction of serotonin neurons on basal and fenfluramine-induced serotonin release in striatum. Synapse 20:2(99-105)1995 Jun

7862845. Kirby LG, Rowan GA, Smith RL, Lucki I, Discriminative stimulus properties of the benzodiazepine receptor inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). Psychopharmacology (Berl) 113:3-4(351-60)1994 Jan

22677142. Reyes BAS, Szot P, Sikkema C, Cathel AM, Kirby LG, Van Bockstaele EJ, Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure, Exp Neurol 236:2(327-35)2012 Aug

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University of Pennsylvania

Intro. Biological Basis of Behavior lecture on Anxiety and Affective Disorders, 1994

Behavioral Pharmacology lecture on Behavioral Models of Anti-Anxiety Drugs,1995

Adv. Topics Neuropsychopharmacology lecture on Stress and Affective Disorders, 2004

Molecular Pharmacology lecture on Introduction to Neuropeptides, 2002-2005

 

Temple University School of Medicine

Medical Neuroscience lectures on Neurochemistry of Behavior: Motivation, Feeding and Selective Attention, Neurochemistry of Behavior: The Sleep/Wake Cycle, Limbic System and Emotion, Autonomic Nervous System, Gonadal Hormones and Mood; 2006- present

 

Pharmacology of Drugs of Abuse lecture on Benzodiazepines and Sedatives, 2006-present

 

Neuropharmacology lecture on Serotonin, Stress and Psychopathology, 2007-present

 

Translational Neuroscience lecture on Mood Disorders and Substance Abuse: Basic Science, 2011-present

 

Seminars in Cell Biology, faculty moderator, 2005-present

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Postdoctoral Fellows

Margaret Sperow, 2012-present

Chen Li, 2011-present
Rani Vasudeva, 2011-present

Daniel Staub, 2007-2011

Graduate Students

Jason Lunden (PhD Program), 2007-present

Silke Heinisch (MD/PhD Program), 2005 - 2008

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