Neuroscience
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Frontal areas are thought to be the coordinators of working memory processes by controlling other brain areas reflected by oscillatory activities like frontal-midline theta (4-7 Hz). With aging substantial changes can be observed in the frontal brain areas, presumably leading to age-associated changes in cortical correlates of cognitive functioning. The present study aimed to test whether altered frontal-midline theta dynamics during working memory maintenance may underlie the capacity deficits observed in older adults. 33-channel EEG was recorded in young (18-26 years, N=20) and old (60-71 years, N=16) adults during the retention period of a visual delayed match-to-sample task, in which they had to maintain arrays of 3 or 5 colored squares. ⋯ Old participants showed reduced frontal theta activity during both tasks compared to the young group. In the young memory maintenance-related frontal-midline theta activity was shown to be sensitive both to the increased memory demands and to efficient subsequent memory performance, whereas the old adults showed no such task-related difference in the frontal theta activity. The decrease of frontal-midline theta activity in the old group indicates that cerebral aging may alter the cortical circuitries of theta dynamics, thereby leading to age-associated decline of working memory maintenance function.
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Experiences with a high degree of emotional salience are better remembered than events that have little emotional context and the amygdala is thought to play an important role in this enhancement of memory. Visual recognition memory relies on synaptic plasticity in the perirhinal cortex but little is known about the mechanisms that may underlie emotional enhancement of this form of memory. There is good evidence that noradrenaline acting via β-adrenoceptors (β-ADRs) can enhance memory consolidation. ⋯ However, at the LA-PRh input, combining stimulation that is subthreshold for LTP induction with isoprenaline results in long-lasting potentiation. Isoprenaline-induced and isoprenaline plus subthreshold stimulation-induced potentiation in the PRh-PRh and LA-PRh inputs, respectively were both dependent on activation of NMDARs (N-methyl-D-aspartate receptors), voltage-gated calcium channels and PKA (protein kinase A). Understanding the mechanisms of amygdala-perirhinal cortex plasticity will allow a greater understanding of how emotionally-charged events are remembered.
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Somatostatin (SRIF) modulates neurotransmitter release by activating the specific receptors (sst1-sst5). Our previous study showed that sst5 receptors are expressed in rat retinal GABAergic amacrine cells. Here, we investigated modulation of GABA release by SRIF in cultured amacrine cells, using patch-clamp techniques. ⋯ However, SRIF persisted to suppress the sIPSCs in the presence of KT5823, a protein kinase G (PKG) inhibitor. Moreover, pre-incubation with Bis IV, a protein kinase C (PKC) inhibitor, or pre-application of xestospongin C, an inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor, SRIF still suppressed the sIPSC frequency. All these results suggest that SRIF suppresses GABA release from the amacrine cells by inhibiting presynaptic Ca2+ channels, in part through activating sst5/sst2 receptors, a process that is mediated by the intracellular cAMP-PKA signaling pathway.
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Interactions between neurotransmitters and the immune system represent new prospects for understanding neuroinflammation and associated neurological disease. GABA is the chief inhibitory neurotransmitter but its actions on immune pathways in the brain are unclear. In the present study, we investigated GABAergic transport in conjunction with neuroinflammation in models of multiple sclerosis (MS). ⋯ In vivo GNX treatment reduced Gat-2, Cd3ε, MhcII, and Xbp-1/s expression in spinal cords following EAE induction (p<0.05), which was correlated with improved neurobehavioral outcomes and reduced neuroinflammation, demyelination and axonal injury. These findings highlight altered GABAergic transport through GAT-2 induction during neuroinflammation. GABA transport and neuroinflammation are closely coupled but regulated by GNX, pointing to GABAergic pathways as therapeutic targets in neuroinflammatory diseases.
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Memantine (MEM) is used for improving the cognitive impairments of the patients suffering from Alzheimer's disease (AD) by multiple neuroprotective mechanisms. However, it is still not clear whether nerve growth factor (NGF) signaling is involved in the mechanisms of MEM. The present study investigated the neuroprotective effects of MEM treatment on the cognitive performance and amyloidosis in APP/PS1 transgenic mice, and disclosed the NGF-related mechanism of MEM. ⋯ Simultaneously, MEM also inhibited NGF/p75(NTR) signaling via decreasing the cleavage substrate of p75(NTR), increasing the JNK2 phosphorylation and decreasing the levels of p53 and cleaved-caspase 3. Therefore, the dual-regulation on NGF signaling was attributed to the improvements of cognitive deficits and Aβ depositions in APP/PS1 mice. In conclusion, MEM treatment activated the NGF/TrkA signaling, and inhibited the p75(NTR) signaling in APP/PS1 mice to ameliorate the behavioral deficits and amyloidosis, indicating that NGF signaling was a new potential target of MEM treatment for AD therapy.