Neuroscience
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Subpopulations of neurons in the median preoptic nucleus (MnPO) located within the lamina terminalis contribute to thermoregulatory, cardiovascular and hydromineral homeostasis, and sleep-promotion. MnPO is innervated by lateral hypothalamic neurons that synthesize and secrete the arousal-promoting and excitatory orexin (hypocretin) neuropeptides. To evaluate the hypothesis that orexins modulate the excitability of MnPO neurons, we used patch-clamp recording techniques applied in rat brain slice preparations to assess the effects of exogenously applied orexin A and orexin B peptides on their intrinsic and synaptic properties. ⋯ Orexins did not attenuate the properties of excitatory (n=4) or inhibitory (n=7) postsynaptic currents evoked by subfornical organ stimulation. By contrast, orexins applications induce a significant increase in both frequency and amplitude of spontaneous glutamatergic postsynaptic currents (5/7 cells) but had no influence on spontaneous GABAergic currents (6/6 cells). Thus, in addition to a direct postsynaptic receptor-mediated excitation, orexins can also increase the excitability of MnPO neurons via increasing their excitatory inputs, presumably through an orexin receptor-mediated excitation of local glutamatergic neurons whose axons project to MnPO neurons.
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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.