Neuroscience
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The basal forebrain (BF) plays an important role in modulating cortical activity and influencing attention, learning and memory. These activities are fulfilled importantly yet not entirely by cholinergic neurons. Noncholinergic neurons also contribute and comprise GABAergic neurons and other possibly glutamatergic neurons. ⋯ Moreover, through the presence of PAG, a proportion of ACh- and GABA-synthesizing neurons also has the capacity to synthesize Glu. In sections dual fluorescent immunostained for vesicular transporters, vesicular glutamate transporter (VGluT) 3 and not VGluT2 was present in the cell bodies of most PAG+ and ChAT+ and half the GAD+ cells. Given previous results showing that VGluT2 and not VGluT3 was present in BF axon terminals and not colocalized with VAChT or VGAT, we conclude that the BF cell population influences cortical and subcortical regions through neurons which release ACh, GABA or Glu from their terminals but which in part can also synthesize and release Glu from their soma or dendrites.
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In the present study we combined FM 1-43 imaging and electrophysiological recording of miniature end-plate currents (MEPCs) to determine the role of extracellular calcium in synaptic vesicle exo- and endocytosis at the frog motor nerve terminals. We replaced extracellular Ca2+ ions with other bivalent cations (Sr2+, Ba2+, Cd2+, Mg2+) or used a calcium-free solution and monitored fluorescent staining of the nerve terminals in the presence of caffeine, which promotes the release of Ca2+ from intracellular stores. Caffeine has induced FM1-43 internalization only in the presence of bivalent cations in the external solution. ⋯ This effect of a calcium-free solution was not due to a decrease in exocytosis, because caffeine-induced FM1-43 unloading from the previously loaded nerve terminals, as well as a degree of the MEPCs frequency increase, was unchanged. We conclude that the presence of Ca2+ or other bivalent cations in extracellular space is necessary for endocytosis but not for exocytosis of synaptic vesicles, while transmitter release is promoted by efflux of Ca2+ from intracellular stores. The effect of extracellular Ca2+ on endocytosis might be driven by the non-specific interactions with membrane lipids.
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Connections of motor areas in the frontal cortex of prosimian galagos (Otolemur garnetti) were determined by injecting tracers into sites identified by microstimulation in the primary motor area (M1), dorsal premotor area (PMD), ventral premotor area (PMV), supplementary motor area (SMA), frontal eye field (FEF), and granular frontal cortex. Retrogradely labeled neurons for each injection were related to architectonically defined thalamic nuclei. Nissl, acetylcholinesterase, cytochrome oxidase, myelin, parvalbumin, calbindin, and Cat 301 preparations allowed the ventral anterior and ventral lateral thalamic regions, parvocellular and magnocellular subdivisions of ventral anterior nucleus, and anterior and posterior subdivisions of ventral lateral nucleus of monkeys to be identified. ⋯ M1 receives major inputs from the posterior subdivision of ventral lateral nucleus while premotor areas receive major inputs from anterior parts of ventral lateral nucleus (the anterior subdivision of ventral lateral nucleus and the anterior portion of posterior subdivision of ventral lateral nucleus). PMD and SMA have connections with more dorsal parts of the ventral lateral nucleus than PMV. The results suggest that galagos share many subdivisions of the motor thalamus and thalamocortical connection patterns with simian primates, while having less clearly differentiated subdivisions of the motor thalamus.
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Men are typically reported to have higher pain thresholds than women. Gonadal hormones, particularly testosterone for males, may contribute to this effect. This study tested whether changes in the male hormonal milieu early or late in development alter the inflammatory pain induced by carrageenan (CARR, 3%, intraarticular). ⋯ Both doses of morphine increased mechanical and thermal thresholds. However, compared with the control group, 1 mg/kg morphine was equally effective in reducing mechanical hyperalgesia among groups of animals gonadectomized as adults, but less effective in males gonadectomized neonatally. The results suggest that in males: 1. the antihyperalgesic effect of testosterone (or its metabolites) in CARR-induced inflammation is established during development and maintained by circulating levels of testosterone in adulthood; 2. the nociception-related interaction between the opioid and gonadal systems influences the sensitivity to mechanical stimuli and is likely established during the period of sexual differentiation.
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Activation of Akt/protein kinase B has been recently reported to play an important role in ischemic tolerance. We here demonstrate that the decreased protein expression and phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co-immunoprecipitation analysis reveals that Akt physically interacts with Rac1, a small Rho family GTPase required for mixed lineage kinase 3 (MLK3) autophosphorylation, and both this interaction and Rac1-Ser-71 phosphorylation induced by Akt are promoted in preconditioned rats. ⋯ Akt activation protects against apoptotic neuronal death as shown in TUNEL staining following IPC. Intracerebral infusion of LY294002 before IPC reverses the increase in Akt phosphorylation and the decrease in JNK signaling activation, as well as the neuroprotective action of IPC. Our results suggest that activation of pro-apoptotic MLK3/JNK3 cascade can be suppressed through activating anti-apoptotic phosphoinositide 3-kinase/Akt pathway induced by a sublethal ischemic insult, which provides a functional link between Akt and the JNK family of stress-activated kinases in ischemic tolerance.