Reproductive success in the male rat depends on the ability to recognize appropriate sexual cues, motivation to respond to those cues, and coordination of the necessary motor sequences required to optimize sexual performance and an ejaculatory response. Early maternal environment is important in the normal development of copulatory behavior. Manipulation of this early social stimulation results in alterations in male sexual behavior and in the functioning of mediating endocrine and neurotransmitter systems. The present series of studies were designed to explore the effects of early life maternal deprivation and replacement maternal licking-like stimulation on the development of male rat sexual behavior and the neurophysiological mechanisms which mediate sexual performance with specific attention to the dopamine (DA) and androgen systems. Long-Evans male rats were reared with or without their mothers through the use of the artificial rearing (AR) paradigm. Half of the AR rats were provided with licking-like stimulation, consisting of periodic stroking with a paintbrush. In study 1, AR and maternally-reared (MR) rats were tested in adulthood for sexual behavior. Neuronal activation in response to copulation was assessed using an antibody against the protein product of the immediate early gene c-fos in brain regions that sub-serve sexual behavior. Study 2 explored whether sexual behavioral deficits observed in AR males can be reversed by later sexual experience. In this study, animals were sacrificed following a ninth copulatory trial and Fos immunoreactivity, androgen and estrogen-α receptors were assessed. In study 3, the effects of early maternal deprivation on partner preference in both males that are differentially reared, and, female preference towards these males were investigated. This explored if any behavioral deficits observed in AR males could be attributed to differences in their attractivity to females. Study 4 investigated the effects of early maternal deprivation on androgen sensitivity in adult males. Copulatory response to a receptive female was examined post-castration in AR and MR males and again following testosterone replacement. In study 5, levels of extracellular DA were investigated in the nucleus accumbens, an area critical in motivation, prior to and during copulation in sexually experienced AR and MR males using Microdialysis.

Reproductive success in the male rat depends on the ability to recognize appropriate sexual cues, motivation to respond to those cues, and coordination of the necessary motor sequences required to optimize sexual performance and an ejaculatory response. Early maternal environment is important in the normal development of copulatory behavior. Manipulation of this early social stimulation results in alterations in male sexual behavior and in the functioning of mediating endocrine and neurotransmitter systems. The present series of studies were designed to explore the effects of early life maternal deprivation and replacement maternal licking-like stimulation on the development of male rat sexual behavior and the neurophysiological mechanisms which mediate sexual performance with specific attention to the dopamine (DA) and androgen systems. Long-Evans male rats were reared with or without their mothers through the use of the artificial rearing (AR) paradigm. Half of the AR rats were provided with licking-like stimulation, consisting of periodic stroking with a paintbrush. In study 1, AR and maternally-reared (MR) rats were tested in adulthood for sexual behavior. Neuronal activation in response to copulation was assessed using an antibody against the protein product of the immediate early gene c-fos in brain regions that sub-serve sexual behavior. Study 2 explored whether sexual behavioral deficits observed in AR males can be reversed by later sexual experience. In this study, animals were sacrificed following a ninth copulatory trial and Fos immunoreactivity, androgen and estrogen-α receptors were assessed. In study 3, the effects of early maternal deprivation on partner preference in both males that are differentially reared, and, female preference towards these males were investigated. This explored if any behavioral deficits observed in AR males could be attributed to differences in their attractivity to females. Study 4 investigated the effects of early maternal deprivation on androgen sensitivity in adult males. Copulatory response to a receptive female was examined post-castration in AR and MR males and again following testosterone replacement. In study 5, levels of extracellular DA were investigated in the nucleus accumbens, an area critical in motivation, prior to and during copulation in sexually experienced AR and MR males using Microdialysis.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock that is critical in the temporal organization of circadian activity. The SCN coordinates the rhythmic secretion of gonadal hormones, and in turn, reproductive hormones may act on their receptors within the SCN to alter circadian function. Using transgenic mice that over-express androgen receptor (AR) only in neurons, the current study investigated the influence of neural AR on the function of the SCN. In particular, it addressed the effects of androgens on circadian behaviours as well as physiological responses to light within the SCN by measuring Fos response after a phase-shifting light pulse. It was found that transgenic mice demonstrate a smaller increase in Fos expression in response to a light pulse than do wildtypes. Interpretations of our findings, including the possible functional significance of AR within the SCN, are discussed.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock that is critical in the temporal organization of circadian activity. The SCN coordinates the rhythmic secretion of gonadal hormones, and in turn, reproductive hormones may act on their receptors within the SCN to alter circadian function. Using transgenic mice that over-express androgen receptor (AR) only in neurons, the current study investigated the influence of neural AR on the function of the SCN. In particular, it addressed the effects of androgens on circadian behaviours as well as physiological responses to light within the SCN by measuring Fos response after a phase-shifting light pulse. It was found that transgenic mice demonstrate a smaller increase in Fos expression in response to a light pulse than do wildtypes. Interpretations of our findings, including the possible functional significance of AR within the SCN, are discussed.

Learning and memory are complex phenomena; numerous biochemical and neurobiological mechanisms subserving these functions have been identified. A key molecular component involved in learning and memory, the NMDA-R (N-Methyl-D-Aspartate Receptor) is impaired by MK-801(dizocilpine), an antagonist compound. Here I analyze the effects of MK-801 on the performance characteristics of zebrafish (Danio rerio) as these in turn can significantly influence the outcome of learning tasks. Subsequently, I study the effects of MK-801 on the acquisition, consolidation, and recall of memory in a plus maze, a new task I adapted from zebrafish literature. Although MK-801 seemed to have no effect on acquisition of memory in zebrafish, it disrupted their ability to consolidate and recall in the plus maze, echoing results found in rodent literature. Combined, these results suggest that zebrafish can be used as a tool to further advance the discovery of learning and memory.

Learning and memory are complex phenomena; numerous biochemical and neurobiological mechanisms subserving these functions have been identified. A key molecular component involved in learning and memory, the NMDA-R (N-Methyl-D-Aspartate Receptor) is impaired by MK-801(dizocilpine), an antagonist compound. Here I analyze the effects of MK-801 on the performance characteristics of zebrafish (Danio rerio) as these in turn can significantly influence the outcome of learning tasks. Subsequently, I study the effects of MK-801 on the acquisition, consolidation, and recall of memory in a plus maze, a new task I adapted from zebrafish literature. Although MK-801 seemed to have no effect on acquisition of memory in zebrafish, it disrupted their ability to consolidate and recall in the plus maze, echoing results found in rodent literature. Combined, these results suggest that zebrafish can be used as a tool to further advance the discovery of learning and memory.

Excitatory M5 muscarinic acetylcholine receptors are expressed at the highest level in the brain, in the ventromedial hypothalamus (VMH). M5 knockout (KO) mice emit fewer ultrasonic vocalizations (USVs) during mating, and show 40-50% lesser morphine-induced locomotion as compared to wild-type (WT) mice. Following viral transfection of M5 muscarinic receptors in the ventral tegmentum (VTA), KO mice depict restored mating-induced USVs and enhanced morphine-induced locomotion. The VMH is important for motivational processes, such as, feeding and producing USVs in rats. With a Herpes simplex virus (HSV), the M5 receptor gene was transfected into the VMH of WT mice. M5 transfection into neurons of the VMH increased locomotion in mice injected with 10mg/kg morphine. When a D2-selective dopamine blocker was injected into the same mice, locomotion was drastically reduced. There were no significant differences in amount of USVs produced. VMH may exert its effects on morphine through a DA dependent VTA pathway.

Excitatory M5 muscarinic acetylcholine receptors are expressed at the highest level in the brain, in the ventromedial hypothalamus (VMH). M5 knockout (KO) mice emit fewer ultrasonic vocalizations (USVs) during mating, and show 40-50% lesser morphine-induced locomotion as compared to wild-type (WT) mice. Following viral transfection of M5 muscarinic receptors in the ventral tegmentum (VTA), KO mice depict restored mating-induced USVs and enhanced morphine-induced locomotion. The VMH is important for motivational processes, such as, feeding and producing USVs in rats. With a Herpes simplex virus (HSV), the M5 receptor gene was transfected into the VMH of WT mice. M5 transfection into neurons of the VMH increased locomotion in mice injected with 10mg/kg morphine. When a D2-selective dopamine blocker was injected into the same mice, locomotion was drastically reduced. There were no significant differences in amount of USVs produced. VMH may exert its effects on morphine through a DA dependent VTA pathway.

Research suggests that brain growth follows an abnormal trajectory in children with autism spectrum disorders (ASD). A better understanding of when and how patterns of brain development diverge from that seen in typically developing children could yield insight into the etiology of the disorder, and resulting symptomatology. To investigate this hypothesis, three studies examined the relation between structural and functional brain measures and age in a group of children with an ASD, aged 6 to 14 years. Age by group interactions were found in all three studies, providing further evidence that brain development may follow an atypical trajectory in ASD. Study 1: Differences in the relation between structural indices and age were found in grey matter volume, surface area and thickness, as well as in cortical thickness of specific regions in the left inferior frontal gyrus (BA 44) and left precuneus. These measures of grey matter structure generally decreased with age in the ASD children, compared to little or no change with age in the typically developing children. Study 2: Differences in the relation between age and measures of longitudinal, radial and mean diffusivity were found in frontal, long distant, interhemispheric and posterior white matter tracts; diffusivity decreased with age in the typically developing group, but showed little or no change in the ASD group. Study 3: Differences in the relation between BOLD activation on a set-shifting task and age were found in brain regions important for cognitive flexibility, such as areas of prefrontal, right insula and parietal cortex. These effects were mainly due to decreasing activation with age for the ASD group, but increasing or no age-related change in the TD group. The findings of these three studies provide converging evidence in support of an hypothesis of dysregulated brain development in this population, which could have significant, compounding effects on the development of neural connectivity, and contribute to atypical cognitive development in children with ASD.

Research suggests that brain growth follows an abnormal trajectory in children with autism spectrum disorders (ASD). A better understanding of when and how patterns of brain development diverge from that seen in typically developing children could yield insight into the etiology of the disorder, and resulting symptomatology. To investigate this hypothesis, three studies examined the relation between structural and functional brain measures and age in a group of children with an ASD, aged 6 to 14 years. Age by group interactions were found in all three studies, providing further evidence that brain development may follow an atypical trajectory in ASD. Study 1: Differences in the relation between structural indices and age were found in grey matter volume, surface area and thickness, as well as in cortical thickness of specific regions in the left inferior frontal gyrus (BA 44) and left precuneus. These measures of grey matter structure generally decreased with age in the ASD children, compared to little or no change with age in the typically developing children. Study 2: Differences in the relation between age and measures of longitudinal, radial and mean diffusivity were found in frontal, long distant, interhemispheric and posterior white matter tracts; diffusivity decreased with age in the typically developing group, but showed little or no change in the ASD group. Study 3: Differences in the relation between BOLD activation on a set-shifting task and age were found in brain regions important for cognitive flexibility, such as areas of prefrontal, right insula and parietal cortex. These effects were mainly due to decreasing activation with age for the ASD group, but increasing or no age-related change in the TD group. The findings of these three studies provide converging evidence in support of an hypothesis of dysregulated brain development in this population, which could have significant, compounding effects on the development of neural connectivity, and contribute to atypical cognitive development in children with ASD.