Neuroscience
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The mammalian hippocampus continues to generate new neurons throughout life. Experiences such as exercise, anti-depressants, and stress regulate levels of neurogenesis. Exercise increases adult hippocampal neurogenesis and enhances behavioral performance on rotarod, contextual fear and water maze in rodents. ⋯ Minimal changes in microglia associated with inflammation (using immunohistochemical detection of cd68) were detected at the time of behavioral testing. Irradiation did not reduce gains in performance on rotarod or contextual fear, however it eliminated gain in performance on the water maze. Results support the hypothesis that intact exercise-induced hippocampal neurogenesis is required for improved spatial memory, but not motor performance or contextual fear in C57BL/6J mice.
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In some neurons, muscarinic M(1)-class receptors control L-type (Ca(V)1) Ca(2+)-channels via protein kinase C (PKC) or calcineurin (phosphatase 2B; PP-2B) signaling pathways. Both PKC and PP-2B pathways start with phospholipase C (PLC) activation. In contrast, P/Q- and N-type (Ca(V)2.1, 2.2, respectively) Ca(2+)-channels are controlled by M(2)-class receptors via G proteins that may act, directly, to modulate these channels. ⋯ However, PKC inhibitors (bisindolylmaleimide I and PKC-1936) only block modulation of currents through N and L types Ca(2+) channels; while the modulation of P/Q-type Ca(2+) channels remains unaffected. These results show that different branches of the same signaling cascade can be used to modulate different Ca(2+) channels. Finally, we found no evidence of calcineurin modulating these Ca(2+) channels during M(1)-receptor activation, although, in the same cells, we demonstrate functional PP-2B by activating dopaminergic D(2)-receptor modulation.
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Estradiol modulates dendritic spine morphology and synaptic protein expression in the rodent hippocampus, as well as hippocampal-dependent learning and memory. In the rat, these effects may be mediated through nongenomic steroid signaling such as estradiol activation of the Akt and LIM kinase (LIMK) pathways, in addition to genomic signaling involving estradiol upregulation of brain-derived neurotrophic factor expression (BDNF). Due to the many species differences between mice and rats, including differences in the hippocampal response to estradiol, it is unclear whether estradiol modulates these pathways in the mouse hippocampus. ⋯ Cycle phase also modulated expression of the pre- and post-synaptic markers synaptophysin and post-synaptic density 95. However, cycle phase did not influence performance on an object placement test of spatial memory, although this task is known to be sensitive to the complete absence of ovarian hormones. The findings suggest that endogenous estradiol and progesterone produced by the ovaries modulate specific signaling pathways governing actin remodeling, cell excitability, and synapse formation.