Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis: A role for retrograde motors.

Mutations in the genes for components of the dynein-dynactin complex disrupt axon path finding and synaptogenesis during metamorphosis in the Drosophila central nervous system. In order to better understand the functions of this retrograde motor in nervous system assembly, we analyzed the path finding and arborization of sensory axons during metamorphosis in wild-type and mutant backgrounds. In wild-type specimens the sensory axons first reach the CNS 6-12 h after puparium formation and elaborate their terminal arborizations over the next 48 h. In Glued1 and Cytoplasmic dynein light chain mutants, proprioceptive and tactile axons arrive at the CNS on time but exhibit defects in terminal arborizations that increase in severity up to 48 h after puparium formation. The results show that axon growth occurs on schedule in these mutants but the final process of terminal branching, synaptogenesis, and stabilization of these sensory axons requires the dynein-dynactin complex. Since this complex functions as a retrograde motor, we suggest that a retrograde signal needs to be transported to the nucleus for the proper termination of some sensory neurons.

Estradiol and progesterone influence the response of ventromedial hypothalamic neurons to tactile stimuli associated with female reproduction.

Stimulation of the vagina and cervix, provided by the male during copulation or manually with a probe, causes many behavioral and endocrine changes associated with female reproduction in rats. Previously, we found that vaginal-cervical stimulation (VCS), by mating or manual probing, increases the expression of Fos-immunoreactivity (Fos-IR) in discrete populations of neurons in the preoptic area, mediobasal hypothalamus and midbrain, suggesting that these neurons respond to VCS. The purpose of the present study was to determine if hormonal priming would increase the number of Fos-IR cells following VCS. Contrary to our hypothesis, in Experiment 1 priming animals with a behaviorally effective dose of 17 beta-estradiol benzoate followed 48 h later by progesterone caused a trend towards a decrease in the number of VCS-induced Fos-IR cells in the ventromedial hypothalamus. In Experiment 2, which was done to confirm this decrease in VCS-induced Fos-IR neurons by hormones, this effect was found to be statistically significant. Furthermore, this hormone-induced decrease in VCS-responsive cells was localized to the ventromedial nucleus of the hypothalamus, an area rich in estrogen and progestin receptors. No effects of hormone treatment on VCS-induced Fos-IR were observed in any other brain regions analyzed. These findings suggest that steroid hormones may elicit some of their effects on female reproductive behavior and physiology by altering the responsiveness of ventromedial nucleus neurons to vaginal-cervical stimulation.

Fos expression in the rat brain following vaginal-cervical stimulation by mating and manual probing.

Vaginal-cervical stimulation (VCS), provided by mating or manual probing, induces many reproductive behavioral and endocrine changes in female rats. These changes include an increase in lordosis duration, heat termination and pseudopregnancy. Electrophysiological and [14C]2-deoxy-D-glucose studies collectively show that neurons in the medial preoptic area, ventromedial hypothalamus and midbrain central gray respond to manual VCS. In the present study we immunocytochemically labeled brain sections for Fos, the protein product of the immediate early gene c-fos, to detect VCS-responsive neurons in hormone-primed animals receiving VCS by mating or manual probing. In Experiment 1, females receiving mounts and intromissions were compared to: 1) vaginally-masked females receiving mounts but no VCS, 2) females exposed to an intact anesthetized male or 3) females not exposed to males or the testing arena. Those animals receiving VCS showed a dramatic increase in the number of Fos-immunoreactive cells in the medial preoptic area, posterodorsal portion of the medial amygdala and bed nucleus of the stria terminalis, as well as the dorsomedial hypothalamus, ventromedial hypothalamus and midbrain central gray. These effects of VCS were confirmed in Experiment 2 in animals receiving manual vaginal-cervical probing. These findings extend previous electrophysiological and [14C]2-deoxy-D-glucose studies by providing evidence that additional brain areas respond to VCS by mating, as well as manual probing.