The long range goals of this project are to identify the neural circuit basis of gonadal hormone influence over cortical function and dysfunction in man. Psychometric studies in men, women, and patients diagnosed with congenital hormonal dysfunction, e.g., Turner's syndrome, have established that particular cortical functions are targets of the organizing effects of gonadal steroid stimulation. The striking gender differences in facets of incidence, symptoms and/or clinical outcome of psychiatric diseases such as schizophrenia, autism and Tourette's syndrome have also led to the hypothesis that gonadal hormones may have bearing on the cortical dysfunction that is the hallmark of these devastating disorders. Knowledge of the structural endpoints of hormone stimulation in the cerebrum, however, is limited to effects on cortical volume, thickness, and dendritic architecture. This current state of knowledge precludes any precise understanding of the functionally relevant hormonally-induced neural substrates which may mediate expression of gender-specific cortical function. In order to begin to understand the contributions of the structural actions of gonadal steroids to cortical information processing, the studies of this proposal will examine the effects of hormone stimulation on cortical circuit organization. Using quantitative indices of synaptic density, intrinsic circuit organization, neurochemically identified innervation, and dendritic structure as dependent variables, the studies of this proposal will explore the structural consequences, biological underpinnings and timing of gonadal hormone stimulation of cortical circuit organization in functionally specialized cortical domains of the Long Evans rat. By pairing fine-grained anatomical methods with classical hormone manipulation paradigms, it is predicted that evidence for regional laminar, and/or temporal specificity in the actions of gonadal steroids on cortical circuit structure will emerge. These findings should provide foundations for specific, testable hypotheses of cortical circuit vulnerability in particular psychiatric disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS035422-04
Application #
2771962
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Kitt, Cheryl A
Project Start
1995-09-30
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Kritzer, M F (2002) Regional, laminar, and cellular distribution of immunoreactivity for ER alpha and ER beta in the cerebral cortex of hormonally intact, adult male and female rats. Cereb Cortex 12:116-28
Kritzer, M F; Pugach, I (2001) Administration of tamoxifen but not flutamide to hormonally intact, adult male rats mimics the effects of short-term gonadectomy on the catecholamine innervation of the cerebral cortex. J Comp Neurol 431:444-59
Kritzer, M F; McLaughlin, P J; Smirlis, T et al. (2001) Gonadectomy impairs T-maze acquisition in adult male rats. Horm Behav 39:167-74
Kritzer, M F (2000) Effects of acute and chronic gonadectomy on the catecholamine innervation of the cerebral cortex in adult male rats: insensitivity of axons immunoreactive for dopamine-beta-hydroxylase to gonadal steroids, and differential sensitivity of axons immunoreact J Comp Neurol 427:617-33
Kritzer, M F; Kohama, S G (1999) Ovarian hormones differentially influence immunoreactivity for dopamine beta- hydroxylase, choline acetyltransferase, and serotonin in the dorsolateral prefrontal cortex of adult rhesus monkeys. J Comp Neurol 409:438-51
Kritzer, M F; Adler, A; Marotta, J et al. (1999) Regionally selective effects of gonadectomy on cortical catecholamine innervation in adult male rats are most disruptive to afferents in prefrontal cortex. Cereb Cortex 9:507-18
Adler, A; Vescovo, P; Robinson, J K et al. (1999) Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats. Neuroscience 89:939-54
Venkatesan, C; Kritzer, M F (1999) Perinatal gonadectomy affects corticocortical connections in motor but not visual cortex in adult male rats. J Comp Neurol 415:240-65
Finley, S K; Kritzer, M F (1999) Immunoreactivity for intracellular androgen receptors in identified subpopulations of neurons, astrocytes and oligodendrocytes in primate prefrontal cortex. J Neurobiol 40:446-57
Kritzer, M F; Kohama, S G (1998) Ovarian hormones influence the morphology, distribution, and density of tyrosine hydroxylase immunoreactive axons in the dorsolateral prefrontal cortex of adult rhesus monkeys. J Comp Neurol 395:1-17

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