The goal of this research is to elucidate the neural mechansims by which specific forebrain, brainstem and spinal cord sites coordinate male reproductive behavior. Our new preliminary studies suggest a potential pathway that mediates forebrain influences on L6/S1 cord. This circuit comprises the MPO-->PGi-->spinal cord. The nucleus paragigantocellularis (PGi) in the ventrolateral medulla receives direct input from the MPO and projects heavily to the L6/S1 cord. Our preliminary data show that descending projections from the PGi selectively terminate within the motoneuronal pools that innervate the pelvic viscera.
Aim 1 will test the hypothesis that MPO projections target PGi neruons that project to the lumbosacral spinal cord. A combined approach using both antero and retrograde tracers will be used to delineate the anatomical organization of MPO-->PGi-->spinal cord circuit. Spinal sexual reflexes are under tonic descending inhibition, presumably via input from the PGi. Recent studies suggest that MPO neuronal activity must increase for normal male reproductive behavior to occur. We postulate therefore that increased MPO activity before and during copulation functions, in part, to reduce the tonic inhibition (""""""""disinhibition hypothesis"""""""") on spinal motor reflexes.
Aim 2 employs coordinate neuroanatomical, immunocytochemical and electrophysiological techniques to test this disinhibition hypothesis: MPO activation inhibits PGi-->spinal cord neurons allowing for spinally mediated sexual reflexes to occur. The MPO and its output to the PGi are central for the initiation and maintenance of male sex behavior.
Aim 3 tests the hypothesis that the MPO-->PGi circuit is selectively engaged during male sex behavior; activation of this circuit during copulation inhibits PGi pudendal premotor neurons via the release of GABA. As copulation is a steroid dependent behavior, we predict that the critical neural substrates along this MPO-->PGi-->spinal cord circuit will contain receptors for gonadal steroids. These studies will provide the first functional characterization of the MPO-->PGi-->spinal cord pathway. Together, these studies will provide detailed anatomical and physiological data on a neural circuit regulating male sex behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH059187-04
Application #
6477073
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (01))
Project Start
1998-12-01
Project End
2003-11-30
Budget Start
2001-12-01
Budget End
2003-11-30
Support Year
4
Fiscal Year
2002
Total Cost
$183,368
Indirect Cost
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201