Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice.

Norepinephrine (NE), and specific adrenoceptors, have been reported to influence distinct aspects of adult hippocampal neurogenesis, including latent stem cell activation, progenitor proliferation, and differentiation. These findings are predominantly based on the use of pharmacological approaches in both in vitro and in vivo systems. Here, we sought to assess the consequences of genetic ablation of NE on adult hippocampal neurogenesis, by examining dopamine ß hydroxylase knockout (Dbh -/-) mice, which lack NE from birth. We find that Dbh -/- mice exhibit no difference in adult hippocampal progenitor proliferation and survival. Further, the number of immature newborn neurons, labeled using stage-specific developmental markers within the hippocampal neurogenic niche, was also unaltered in Dbh -/- mice. In contrast, the noradrenergic neurotoxin DSP-4, which had previously been shown to reduce adult hippocampal neurogenesis in rats, also resulted in a decline in hippocampal progenitor proliferation in C57/Bl6N mice. These findings indicate that pharmacological lesioning of noradrenergic afferents in adulthood, but not the complete genetic loss of NE from birth, impairs adult hippocampal neurogenesis in mice.

Neural and behavioral plasticity across the female reproductive cycle.

Sex is fundamental for the evolution and survival of most species. However, sex can also pose danger, because it increases the risk of predation and disease transmission, among others. Thus, in many species, cyclic fluctuations in the concentration of sex hormones coordinate sexual receptivity and attractiveness with female reproductive capacity, promoting copulation when fertilization is possible and preventing it otherwise. In recent decades, numerous studies have reported a wide variety of sex hormone-dependent plastic rearrangements across the entire brain, including areas relevant for female sexual behavior. By contrast, how sex hormone-induced plasticity alters the computations performed by such circuits, such that collectively they produce the appropriate periodic switches in female behavior, is mostly unknown. In this review, we highlight the myriad sex hormone-induced neuronal changes known so far, the full repertoire of behavioral changes across the reproductive cycle, and the few examples where the relationship between sex hormone-dependent plasticity, neural activity, and behavior has been established. We also discuss current challenges to causally link the actions of sex hormones to the modification of specific cellular pathways and behavior, focusing on rodents as a model system while drawing a comparison between rodents and humans wherever possible.

Opposing effects of α2- and ß-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis.

Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and ß-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of ß-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and ß-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis.