Neuroscience
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Hindbrain-derived stimuli restrain the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) reproductive neuroendocrine axis during energy insufficiency. Interruption of food intake, planned or unplanned, is emblematic of modern life. This study investigated the premise that the hindbrain energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibits reproductive neuroendocrine function in short term, e.g. 18-h food-deprived (FD) estradiol (E)-implanted ovariectomized female rats. ⋯ Lateral ventricular delivery of the NO donor 3-morpholinosydnonimine (SIN-1) reversed inhibitory GnRH and LH responses to FD in high-E rats, and normalized rPO Vglut2, anteroventral periventricular KiSS1, and dorsomedial hypothalamic RFRP-3 mRNA and/or protein profiles. Data show that FD curtails reproductive neuroendocrine outflow by hindbrain AMPK-dependent mechanisms in the presence of peak estrous cycle E levels. Results indicate that neural networks linking this sensor to GnRH neurons likely involve NO signaling, which may function upstream of one or more neurotransmitters identified here by SIN-1-reversible inhibitory responses to FD.
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Electrical coupling mediated by connexin36-containing gap junctions that form electrical synapses is known to be prevalent in the central nervous system, but such coupling was long ago reported also to occur between cutaneous sensory fibers. Here, we provide evidence supporting the capability of primary afferent fibers to engage in electrical coupling. In transgenic mice with enhanced green fluorescent protein (eGFP) serving as a reporter for connexin36 expression, immunofluorescence labeling of eGFP was found in subpopulations of neurons in lumbar dorsal root and trigeminal sensory ganglia, and in fibers within peripheral nerves and tissues. ⋯ Expression of eGFP was also found in various proportions of sensory ganglion neurons containing transient receptor potential (TRP) channels, including TRPV1 and TRPM8. Ganglion cells labeled for isolectin B4 and tyrosine hydroxylase displayed very little co-localization with eGFP. Our results suggest that previously observed electrical coupling between peripheral sensory fibers occurs via electrical synapses formed by Cx36-containing gap junctions, and that some degree of selectivity in the extent of electrical coupling may occur between fibers belonging to subpopulations of sensory neurons identified according to their sensory modality responsiveness.
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The putative strong anti-nociceptive properties of the antidepressant phenelzine (PLZ) have not been widely explored as a treatment for pain. Antinociceptive effects of PLZ were identified in the formalin model of tonic pain (Mifflin et al., 2016) and in allodynia associated with experimental autoimmune encephalomyelitis, (EAE) a mouse model of multiple sclerosis (Potter et al., 2016). Here, we further clarify the specific types of stimuli and contexts in which PLZ modulates nociceptive sensitivity. ⋯ Superfusion with PLZ (100-300 μM) reduced 1 mM glutamate-evoked calcium responses. This was blocked by pretreatment with the 5HT1A-receptor antagonist WAY-100,635, but not the alpha-2 adrenergic antagonist idazoxan. We conclude that PLZ exerts antinociceptive effects through a 5-HT/5HT1AR-dependent inhibition of neuronal responses within nociceptive circuits of the dorsal horn.
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To study the responsive neural activities in the primary visual cortex (V1) of retinal degeneration (RD) models, experiments involving the wild-type (WT) and RD rats were conducted. The neural responses in the V1 were recorded extracellularly, while a visual stimulus with varied light intensity was given to the subjects. First, the firing rate and its relationship with light intensity were compared between the WT and RD groups. ⋯ However, the information transmission performance of the RD model was similar to that of the WT group in the context of LFP activity. Therefore, for the RD rats, the early stage of the visual system was impaired, while the later stage of the visual system, V1, was able to capture the information about the visual stimulus, especially at the population level. Thus, this pathway could be used to restore visual ability, such as by visual prostheses.
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Regulator of G protein signaling (RGS) proteins are negative regulators of heterotrimeric G proteins that act by accelerating Gα-mediated GTPase activity to terminate G protein-coupled receptor-associated signaling. RGS8 is expressed in several brain regions involved with movement and mood. To investigate the role of RGS8 in vivo, we generated transgenic mice overexpressing brain RGS8 (RGS8tg). ⋯ Immunohistochemical analyses revealed significant elongation of MCHR1-positive cilia in the CA1 region of RGS8tg compared with WT. Taken together, these findings suggest that RGS8 participates in modulation of depression-like behavior through ciliary MCHR1 expressed in the CA1 region. The present study may support the possible modulation of RGS8 function in mood disorders.