Neuroscience
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The suprachiasmatic nucleus (SCN), the dominant circadian pacemaker in mammalian brain, sends axonal projections to the hypothalamic paraventricular nucleus (PVN), a composite of magno- and parvocellular neurons. This neural network likely offers SCN output neurons a means to entrain diurnal rhythmicity in various autonomic and neuroendocrine functions. Earlier investigations using patch-clamp recordings in slice preparations have suggested differential innervation by SCN efferents to magnocellular versus parvocellular PVN cells. ⋯ At 1 microM where baclofen had no significant postsynaptic effect, evidence of activation of presynaptic GABA(B) receptors included reduction in SCN-evoked IPSCs and EPSCs with no change in their kinetics, and paired-pulse depression that was sensitive to both baclofen and saclofen. Baclofen also induced significant reductions in frequency but not amplitudes of miniature IPSCs and EPSCs. These observations suggest that levels of synaptically released GABA from the terminals of SCN output neurons can influence the relative contribution of pre- versus postsynaptic GABA(B) receptors in modulating both excitatory and inhibitory SCN innervation to parvocellular PVN neurons.
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The neurochemistry of aggression and rage has largely focused on the roles played by neurotransmitters and their receptor mechanisms. In contrast, little attention has been given to the possible functions of other substances. Interleukin-1beta is an immune and brain-derived cytokine that is present in the hypothalamus. ⋯ In the third experiment, pretreatment with a selective 5-HT2 receptor antagonist, LY-53857, blocked the facilitating effects of interleukin-1beta upon defensive rage. These findings reveal for the first time that brain cytokines can dramatically alter aggressive behavior. In particular, interleukin-1beta in the medial hypothalamus potentiates defensive rage behavior elicited from the periaqueductal gray in the cat, and the potentiating effects of interleukin-1beta on this form of emotional behavior are mediated via a 5-HT2 receptor mechanism.
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Comparative Study
Impaired long-term potentiation in obese zucker rats: possible involvement of presynaptic mechanism.
Electrophysiological investigation of basal synaptic transmission and synaptic plasticity in the CA1 region of the hippocampus was carried out in anesthetized obese Zucker rats (OZR). Comparison of the input/output curves of basal field excitatory postsynaptic potential indicates that these are similar in both the OZR and its lean counterpart suggesting that basal synaptic transmission is intact in the OZR. ⋯ Since post-tetanic potentiation and paired pulse facilitation, forms of short-term potentiation of presynaptic origin, are also severely impaired in the OZR, the results imply that impairment of CA1 hippocampal LTP in these obese rats may be due, in part, to impaired presynaptic function. The results emphasize the potential deleterious effect of obesity on learning and memory functions of the CNS.
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Using a rat relapse model, we have shown that infusion of a corticotropin-releasing factor (CRF) receptor antagonist into the median raphe nucleus (MRN) blocks footshock stress-induced reinstatement of alcohol seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured levels of c-fos mRNA in discrete nuclei of the rat brain following exposure to intermittent footshock, which was preceded by intra-MRN infusions of a CRF receptor antagonist, d-Phe CRF (0 or 50 ng). ⋯ Pretreatment with d-Phe CRF in the MRN selectively attenuated the increases in c-fos mRNA induced by footshock in the central nucleus of the amygdala (CeA). These findings are consistent with previous data on the important role for the CeA in stress-induced reinstatement of drug seeking. These results also suggest that inhibition of CeA activity may contribute to the blockade of alcohol-seeking induced by footshock that we have observed following injections of d-Phe into the MRN.
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Focal traumatic injury to the cerebral cortex is associated with early activation of the neuronal isoform of nitric oxide synthase (nNOS), where high concentrations of nitric oxide-derived free radicals elicit extensive DNA damage. Subsequent activation of the nuclear repair enzyme poly(ADP-ribose) polymerase (PARP) causes a severe energy deficit leading to the ultimate demise of affected neurons. Little is known about the temporal relationship of nNOS and PARP activation and the neuroprotective efficacy of their selective blockade in traumatic brain injury. ⋯ In contrast, i.p. AB treatment remained largely ineffective. In conclusion, our data indicate early activation of PARP after cold lesion that is, at least in part, related to nNOS induction and supports the relevance of nNOS and/or PARP inhibition to therapeutic approaches of traumatic brain injury.