The central goal of this project is to determine the structural, physiological, and behavioral consequences of allosteric modulation of GABAA-receptors by neurosteroids in the mitral cell layer of the accessory olfactory bulb (AOB) in defined endocrine environments. Neurosteroids have been implicated in affective disorders that seem to be sensitive to hormonal environments, including depression, postpartum depression, and anxiety. In addition, neurosteroids can modulate the expression of sexual behaviors and may increase the vulnerability to develop psychiatric disease, This study will take advantage of a simple experimental assay to determine the effects of neurosteroids on GABAergic neurotransmission.
In Specific Aim 1, GABAA-currents to three neurosteroids, juvenile, and adult, male and female rats. The sensitivity of GABAA-currents to three neurosteroids; 3alpha, 5alpha- THP, 3alpha-DIOL, and DHEA will be tested. Similarly, in Specific Aim 2 GABAA-currents will be recorded and assessed for neurosteroid sensitivity during different stages of pregnancy and early after parturition.
These aims will determine whether neurosteroids produce sex-specific and hormone-dependent effects or systemic administration or neurosteroids will be provided during neonatal development to determine if these compounds contribute to the sexually dimorphic structure of the AOB mitral cell layer. These experiments will establish whether neurosteroids have an impact in setting up the structure of brain regions associated with sex specific behaviors. Finally, in Specific Aim 4, neurosteroids will be infused into the AOB directly to determine if these compounds can modulate the expression of maternal behaviors in parturient rats.
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