DA recordings in the NAcc by fast-scan voltammetry during electrical stimulation of the medial forebrain bundle confirmed that the NAcc contains a patchwork of fast and slow domains showing significantly different rates of evoked DA release and DA clearance. Moreover, the NAcc domains are substantially different from those in the dorsal striatum. There were no AZD5363 cost signs in the NAcc of short-term plasticity of DA release during multiple consecutive stimuli, and no signs of a domain-dependent autoinhibitory tone. Thus, the NAcc domains are distinct from

each other and from the domains of the dorsal striatum. “
“How the number of docked vesicles is regulated is still unclear. Following chronic activity blockade the number of docked vesicles increases, providing a model through which to address this issue. We tested the hypotheses that the number of docked vesicles is regulated Osimertinib with the size of the terminal, and by the level of Rab3-interacting molecule 1/2 (RIM1/2). We immobilized mouse hippocampal slice

cultures by high-pressure freezing after 3 days of tetrodotoxin treatment and analysed them by electron microscopy. The number of docked vesicles, the size of the active zones and the amount of GluA2 were increased after activity blockade. However, there was no modification of either the total number of synaptic vesicles or the area of presynaptic profiles. Surprisingly, immunocytochemistry showed no change in the mean level of RIM1/2 per terminal but its distribution was modified. Additionally, there was no modification of the mean frequency or amplitude of miniature excitatory postsynaptic currents, but the distribution of amplitudes was modified. These results indicate a specific homeostatic regulation of the synaptic junction. The number of docked vesicles does not seem to be regulated by the amount of RIM1/2. The modification of the distribution, but not the amount, of RIM1/2 may explain the contradiction between the morphological and electrophysiological findings. “
“We have

evaluated the possibility SPTLC1 that the action of voluntary exercise on the regulation of brain-derived neurotrophic factor (BDNF), a molecule important for rat hippocampal learning, could involve mechanisms of epigenetic regulation. We focused the studies on the Bdnf promoter IV, as this region is highly responsive to neuronal activity. We have found that exercise stimulates DNA demethylation in Bdnf promoter IV, and elevates levels of activated methyl-CpG-binding protein 2, as well as BDNF mRNA and protein in the rat hippocampus. Chromatin immunoprecipitation assay showed that exercise increases acetylation of histone H3, and protein assessment showed that exercise elevates the ratio of acetylated : total for histone H3 but had no effects on histone H4 levels.