Neuroscience
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The encoding of reward-predictive stimuli by neurons in the nucleus accumbens (NAcc) depends on integrated synaptic activity from the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) afferent inputs. In a previous study, we found that single electrical stimulation pulses applied to the BLA facilitate mPFC-evoked spiking in NAcc neurons in a timing-dependent manner, presumably by a fast glutamatergic mechanism. In the present study, the ability of repetitive BLA activation to modulate synaptic inputs to NAcc neurons through dopamine- or N-methyl-D-aspartate (NMDA)-dependent mechanisms is characterized. ⋯ This was not attributable to mechanisms involving NMDA or dopamine D1, D2, D3 or D5 receptors, since blockade of these receptors did not affect the BLA-mediated depression. BLA-mediated depression was only evident when the BLA stimulation evoked spikes in the recorded neuron; thus, depolarization of the recorded neuron may be critical for this effect. The ability of the BLA to suppress mPFC-to-NAcc signaling may be a mechanism by which normal or pathologically heightened emotional states disrupt goal-directed behavior in favor of emotionally-driven responses.
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Cerebral glucose hypometabolism is common in temporal lobe epilepsy (TLE). The temporospatial evolution of these metabolic changes during epileptogenesis remains to be determined. We measured the regional normalized cerebral metabolic rate for glucose (nCMRglc) with (18)F-fluorodeoxyglucose (FDG)-small animal positron emission tomography (microPET) in animals receiving systemic pilocarpine application. ⋯ Conversely, the hippocampus and thalamus presented with persistent hypometabolism during epileptogenesis. The cerebellum and pons maintained normal glucose utilization during this process. We also found that severe glucose hypometabolism in the entorhinal cortex during the early phase was correlated with epileptogenesis, indicating the critical role of the entorhinal cortex in the early stages of TLE.
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Antidepressant action may involve stimulation of brain-derived neurotrophic factor (BDNF). BDNF also regulates long-term potentiation (LTP). We hypothesized that the 5-HT and norepinephrine reuptake inhibitor, venlafaxine, would stimulate BDNF expression and alter LTP more effectively than the selective 5-HT reuptake inhibitor, citalopram. ⋯ Input/output function was significantly but equally reduced after 3 weeks of citalopram, venlafaxine, or control treatment. Decreased BDNF protein in citalopram and vehicle control animals, and decreased input/output function may be consequences of individual housing of animals, which we used to ensure proper dosing. Venlafaxine stimulation of BDNF and inhibition of LTP may be related to the reported effectiveness of venlafaxine in treatment of depression.
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The unilateral microinjection of noradrenaline (NA), but not vehicle solution, into the rostromedial preoptic area (POA) elicited simultaneous increases in cutaneous temperatures of the tail and sole of the foot and decreases in the whole-body O(2) consumption rate, heart rate, and colonic temperature in urethane-chloralose-anesthetized rats, suggesting a coordinate increase in heat loss and decrease in heat production. The magnitude of these responses increased dose-dependently over the range of 1-100 pmol, except for the metabolic and bradycardic responses. Similar hypothermic responses were elicited by the microinjection of 40 pmol methoxamine (an alpha(1)-adrenergic agonist), but not by that of clonidine (an alpha(2)-agonist) or isoproterenol (a beta-agonist). ⋯ The microinjection of 130 fmol prostaglandin (PG) E(2) into the NA-sensitive site always elicited thermogenic, tachycardic, and hyperthermic responses. Furthermore, the PGE(2)-induced febrile responses were greatly attenuated by prior administration of NA at the same site. These results demonstrate that NA in the rostromedial POA exerts alpha(1)-adrenoceptor-mediated hypothermic effects and opposes PGE(2)-induced fever.
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Leptin is critical for normal food intake and energy metabolism. While leptin receptor (ObR) function has been well studied in hypothalamic feeding circuitries, the functional relevance of ObR in extrahypothalamic areas is largely unknown. Central regulatory pathways involved in food intake utilize various neuropeptides, such as urocortin 1 (Ucn1), cocaine- and amphetamine-regulated transcript peptide (CART) and nesfatin-1. ⋯ However, their peptide levels were not significantly changed. The peptide level and mRNA of nesfatin-1 were unaffected by fasting. We conclude that npEW-neurons containing Ucn1, CART and nesfatin-1 co-express ObR, and may be involved in leptin-mediated feeding control in male rats only.