This application is directed at better understanding how the brain serotonin system functions under normal conditions. Only through such an understanding will we be able to appreciate (and ameliorate) how its dysfunction is manifested in a variety of clinical pathologies, including, depression, anxiety, obsessive-compulsive disorders, and myoclonus. In order to achieve a necessary level of experimental precision, the proposed experiments focus on single cell recordings in behaving animals. Previous studies have characterized the activity of brain serotonergic neurons across the sleep-wake-arousal cycle, and their response to a variety of environmental and physiological challenges. The proposed studies will extend these analyses to an examination of the activity of these neurons during complex mammalian behavior. In particular, pilot experiments indicate that serotonergic neurons in the rostral (pontine) raphe groups are dramatically activated (2-5 fold) during central pattern generator (CPG) mediated rhythmic behaviors, especially those involving oral-buccal responses (chewing, licking, grooming). Reciprocally, the activity of many (all) of the same neurons is strongly inhibited during orienting responses (as indicated by head and eye movements, hippocampal theta activity, PGO waves, and heart rate deceleration). These initial observations will be tested rigorously, and expanded to encompass the caudal (medullary) group of serotonergic neurons. Three sets of studies are proposed, utilizing single unit recordings, multibarrel microiontophoresis, and in vivo brain microdialysis. I) SEROTONERGIC NEURONAL ACTIVITY AND CPG MEDIATED BEHAVIORS. a) Does a definitive positive relationship exist between the activity of pontine serotonergic neurons and rhythmic behaviors, especially those involving the oral-buccal region? b) Do the medullary groups of serotonergic neurons display a relation to rhythmic behaviors which does not include oral-buccal movements, but that does include movements mediated by more caudal aspects of the neuraxis? c) Are CPG-related increases in neuronal activity accompanied by increased release of serotonin preferentially in those brain regions directly related to the behavior? II) RELATION OF SEROTONERGIC NEURONAL ACTIVITY TO ORIENTING RESPONSES. a) Does a definitive inverse relationship exist between the activity of pontine, but not medullary, serotonergic neurons and orienting behavior? b) Is this decrease in neuronal activity related to eye or head movements, or to afferent inputs? III) ROLE OF THE SOMATODENDRITIC AUTORECEPTOR UPON SEROTONERGIC NEURONAL ACTIVITY UNDER PHYSIOLOGICAL CONDITIONS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH023433-26
Application #
2890265
Study Section
Special Emphasis Panel (NSS)
Project Start
1976-06-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
26
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Princeton University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Kochman, Linda J; Fornal, Casimir A; Jacobs, Barry L (2009) Suppression of hippocampal cell proliferation by short-term stimulant drug administration in adult rats. Eur J Neurosci 29:2157-65
Yap, Jasmine J; Takase, Luiz F; Kochman, Linda J et al. (2006) Repeated brief social defeat episodes in mice: effects on cell proliferation in the dentate gyrus. Behav Brain Res 172:344-50
Kochman, Linda J; Weber, E Todd; Fornal, Casimir A et al. (2006) Circadian variation in mouse hippocampal cell proliferation. Neurosci Lett 406:256-9
Fornal, Casimir A; Martin-Cora, Francisco J; Jacobs, Barry L (2006) ""Fatigue"" of medullary but not mesencephalic raphe serotonergic neurons during locomotion in cats. Brain Res 1072:55-61
Tung, A; Takase, L; Fornal, C et al. (2005) Effects of sleep deprivation and recovery sleep upon cell proliferation in adult rat dentate gyrus. Neuroscience 134:721-3
Martin-Cora, Francisco J; Fornal, Casimir A; Jacobs, Barry L (2005) Single-unit responses of serotonergic medullary raphe neurons to cardiovascular challenges in freely moving cats. Eur J Neurosci 22:3195-204
Takase, Luiz F; Nogueira, Maria Ines; Bland, Sondra T et al. (2005) Effect of number of tailshocks on learned helplessness and activation of serotonergic and noradrenergic neurons in the rat. Behav Brain Res 162:299-306
Takase, Luiz F; Nogueira, Maria Ines; Baratta, Michael et al. (2004) Inescapable shock activates serotonergic neurons in all raphe nuclei of rat. Behav Brain Res 153:233-9
Jacobs, Barry L; Martin-Cora, Francisco J; Fornal, Casimir A (2002) Activity of medullary serotonergic neurons in freely moving animals. Brain Res Brain Res Rev 40:45-52
Martin-Cora, Francisco J; Fornal, Casimir A; Metzler, Christine W et al. (2002) Insulin-induced hypoglycemia decreases single-unit activity of serotonergic medullary raphe neurons in freely moving cats: relationship to sympathetic and motor output. Eur J Neurosci 16:722-34

Showing the most recent 10 out of 68 publications