scholarly journals Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xing Wang ◽  
Xuan Sun ◽  
Hou-Cheng Zhou ◽  
Fei Luo
Keyword(s):  
Prefrontal Cortex ◽  
Molecular Mechanisms ◽  
Glutamate Release ◽  
Myosin Ii ◽  
Pyramidal Cells ◽  
Brain Structures ◽  
Current Data ◽  
Glutamatergic Transmission ◽  
Beneficial Effects ◽  
Layer V

AbstractIt is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activation of β3-AR exerts beneficial effects on cognitive function, the underlying cellular and molecular mechanisms have not been fully determined. In this study, whole cell patch-clamp recordings were employed to investigate the glutamatergic transmission of layer V/VI pyramidal cells in slices of the rat PFC. Our result demonstrated that SR58611A increased AMPA receptor-mediated excitatory postsynaptic currents (AMPAR-EPSCs) through activating pre-synaptic β3-AR. SR58611A enhanced the miniature EPSCs (mEPSCs) and reduced paired-pulse ratio (PPR) of AMPAR-EPSCs suggesting that SR58611A augments pre-synaptic glutamate release. SR58611A increased the number of readily releasable vesicle (N) and release probability (Pr) with no effects on the rate of recovery from vesicle depletion. Influx of Ca2+ through L-type Ca2+ channel contributed to SR58611A-mediated enhancement of glutamatergic transmission. We also found that calmodulin, myosin light chain kinase (MLCK) and myosin II were involved in SR58611A-mediated augmentation of glutamate release. Our current data suggest that SR58611A enhances glutamate release by the Ca2+/calmodulin/MLCK/myosin II pathway.

scholarly journals miR-98-5p plays a critical role in depression and antidepressant effect of ketamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaoli Huang ◽  
Yuanyuan Wang ◽  
Zifeng Wu ◽  
Jiali Xu ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Rapid Onset ◽  
Therapeutic Strategies ◽  
Antidepressant Effect ◽  
Depression Treatment ◽  
Chronic Social Stress ◽  
Beneficial Effects

AbstractKetamine has been demonstrated to be a rapid-onset and long-lasting antidepressant, but its underlying molecular mechanisms remain unclear. Recent studies have emerged microRNAs as important modulators for depression treatment. In this study, we report that miR-98-5p is downregulated in the prefrontal cortex and hippocampus of mice subjected to chronic social stress, while overexpressing it by its agonist alleviates depression-like behaviors. More importantly, we demonstrate that miR-98-5p is upregulated by ketamine administration, while inhibition of it by its antagonist blocks the antidepressant effect of ketamine. Our data implicate a novel molecular mechanism underlying the antidepressant effect of ketamine, and that therapeutic strategies targeting miR-98-5p could exert beneficial effects for depression treatment.

scholarly journals Regulation of glutamate release by heteromeric nicotinic receptors in layer V of the secondary motor region (Fr2) in the dorsomedial shoulder of prefrontal cortex in mouse

Synapse ◽  
2013 ◽  
Vol 67 (6) ◽  
pp. 338-357 ◽  
Author(s):  
Patrizia Aracri ◽  
Alida Amadeo ◽  
Maria Enrica Pasini ◽  
Umberto Fascio ◽  
Andrea Becchetti
Keyword(s):  
Prefrontal Cortex ◽  
Nicotinic Receptors ◽  
Glutamate Release ◽  
Motor Region ◽  
Layer V

Asynchronous Glutamate Release at Autapses Regulates Spike Reliability and Precision in Mouse Neocortical Pyramidal Cells

2020 ◽  
Author(s):  
Junlong Li ◽  
Suixin Deng ◽  
Quansheng He ◽  
Wei Ke ◽  
Yousheng Shu
Keyword(s):  
Prefrontal Cortex ◽  
Glutamate Release ◽  
Pyramidal Cells ◽  
Essential Elements ◽  
Temporal Precision ◽  
Spike Reliability ◽  
Asynchronous Release ◽  
Whole Cell Recordings ◽  
Ca2 Channels ◽  
Cortical Information Processing

Abstract Autapses are self-synapses of a neuron. Inhibitory autapses in the neocortex release GABA in 2 modes, synchronous release and asynchronous release (AR), providing precise and prolonged self-inhibition, respectively. A subpopulation of neocortical pyramidal cells (PCs) also forms functional autapses, activation of which promotes burst firing by strong unitary autaptic response that reflects synchronous glutamate release. However, it remains unclear whether AR occurs at PC autapses and plays a role in neuronal signaling. We performed whole-cell recordings from layer-5 PCs in slices of mouse prefrontal cortex (PFC). In response to action potential (AP) burst, 63% of PCs showed robust long-lasting autaptic AR, much stronger than synaptic AR between neighboring PCs. The autaptic AR is mediated predominantly by P/Q-type Ca2+ channels, and its strength depends on the intensity of PC activity and the level of residual Ca2+. Further experiments revealed that autaptic AR enhances spiking activities but reduces the temporal precision of post-burst APs. Together, the results show the occurrence of AR at PC autapses, the delayed and persistent glutamate AR causes self-excitation in individual PCs but may desynchronize the autaptic PC population. Thus, glutamatergic autapses should be essential elements in PFC and contribute to cortical information processing.

scholarly journals Cannabinoids Modulate Synaptic Strength and Plasticity at Glutamatergic Synapses of Rat Prefrontal Cortex Pyramidal Neurons

2000 ◽  
Vol 83 (6) ◽  
pp. 3287-3293 ◽  
Author(s):  
Nathalie Auclair ◽  
Satoru Otani ◽  
Philippe Soubrie ◽  
Francis Crepel
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Cannabinoid Receptors ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Type I ◽  
Glutamatergic Synaptic Transmission ◽  
Layer V ◽  
Stimulation Of

Cannabinoids receptors have been reported to modulate synaptic transmission in many structures of the CNS, but yet little is known about their role in the prefrontal cortex where type I cannabinoid receptor (CB-1) are expressed. In this study, we tested first the acute effects of selective agonists and antagonist of CB-1 on glutamatergic excitatory postsynaptic currents (EPSCs) in slices of rat prefrontal cortex (PFC). EPSCs were evoked in patch-clamped layer V pyramidal cells by stimulation of layer V afferents. Monosynaptic EPSCs were strongly depressed by bath application (1 μM) of the cannabinoid receptors agonists WIN55212-2 (−50.4 ± 8.8%) and CP55940 (−42.4 ± 10.9%). The CB-1 antagonist SR141716A reversed these effects. Unexpectedly, SR141716A alone produced a significant increase of glutamatergic synaptic transmission (+46.9 ± 11.2%), which could be partly reversed by WIN55212-2. In the presence of strontium in the bath, the frequency but not the amplitude of asynchronous synaptic events evoked in layer V pyramidal cells by stimulating layer V afferents, was markedly decreased (−54.2 ± 8%), indicating a presynaptic site of action of cannabinoids at these synapses. Tetanic stimulation (100 pulses at 100 Hz, 4 trains) induced in control condition, no changes ( n = 7/18), long-term depression (LTD; n = 6/18), or long-term potentiation (LTP; n = 5/18) of monosynaptic EPSCs evoked by stimulation of layer V afferents. When tetanus was applied in the presence of WIN 55,212-2 or SR141716-A (1 μM) in the bath, the proportion of “nonplastic” cells were not significantly changed ( n = 7/15 in both cases). For the plastic ones ( n = 8 in both cases), WIN 55,212-2 strongly favored LTD ( n = 7/8) at the apparent expense of LTP ( n = 1/8), whereas the opposite effect was observed with SR141716-A (7/8 LTP; 1/8 LTD). These results demonstrate that cannabinoids influence glutamatergic synaptic transmission and plasticity in the PFC of rodent.

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