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 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.

Acute Clozapine Suppresses Synchronized Pyramidal Synaptic Network Activity by Increasing Inhibition in the Ferret Prefrontal Cortex

2007 ◽  
Vol 97 (2) ◽  
pp. 1196-1208 ◽  
Author(s):  
Wen-Jun Gao
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Suppressive Effect ◽  
Network Activity ◽  
Cortical Circuitry ◽  
Prefrontal Cortical ◽  
Recurrent Excitation ◽  
Whole Cell Recordings

Recent studies have indicated that impaired neural circuitry in the prefrontal cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine is one of the most effective antipsychotic drugs used for this debilitating disease. Despite its effectiveness, the mechanism by which clozapine acts on prefrontal cortical circuitry remains poorly understood. In this study, in vitro multiple whole cell recordings were performed in slices of the ferret prefrontal cortex. Clozapine, which effectively inhibited the spontaneous synchronized network activities in the prefrontal neurons, achieved the suppressive effect by decreasing the recurrent excitation among pyramidal neurons and by enhancing the inhibitory inputs onto pyramidal cells through a likely network mechanism. Indeed, under the condition of disinhibition, the depressing effects were reversed and clozapine enhanced the recurrent excitation. These results suggest that the therapeutic actions of clozapine in alleviating the positive symptoms of schizophrenia are achieved, at least partially, through the readjustment of synaptic balance between the excitation and inhibition in the prefrontal cortical circuitry.

scholarly journals Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N-type Ca2+ channels and release machinery

2014 ◽  
Vol 132 (1) ◽  
pp. 38-50 ◽  
Author(s):  
Fei Luo ◽  
Si-hai Li ◽  
Hua Tang ◽  
Wei-ke Deng ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Glutamate Release ◽  
Ca2 Channels

scholarly journals Direct brain recordings reveal prefrontal cortex dynamics of memory development

2018 ◽  
Vol 4 (12) ◽  
pp. eaat3702 ◽  
Author(s):  
E. L. Johnson ◽  
L. Tang ◽  
Q. Yin ◽  
E. Asano ◽  
N. Ofen
Keyword(s):  
Prefrontal Cortex ◽  
Recognition Memory ◽  
Scene Perception ◽  
Declarative Memory ◽  
Memory Formation ◽  
Developing Brain ◽  
Memory Development ◽  
Temporal Precision ◽  
Frontal Activity

Prevailing theories link prefrontal cortex (PFC) maturation to the development of declarative memory. However, the precise spatiotemporal correlates of memory formation in the developing brain are not known. We provide rare intracranial evidence that the spatiotemporal propagation of frontal activity supports memory formation in children. Seventeen subjects (6.2 to 19.4 years) studied visual scenes in preparation for a recognition memory test while undergoing direct cortical monitoring. Earlier PFC activity predicted greater accuracy, and subsecond deviations in activity flow between subregions predicted memory formation. Activity flow between inferior and precentral sites was refined during adolescence, partially explaining gains in memory. In contrast, middle frontal activity predicted memory independent of age. These findings show with subsecond temporal precision that the developing PFC links scene perception and memory formation and underscore the role of the PFC in supporting memory development.

Electrophysiological Differences Between Neurogliaform Cells From Monkey and Rat Prefrontal Cortex

2007 ◽  
Vol 97 (2) ◽  
pp. 1030-1039 ◽  
Author(s):  
N. V. Povysheva ◽  
A. V. Zaitsev ◽  
S. Kröner ◽  
O. A. Krimer ◽  
D. C. Rotaru ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Input Resistance ◽  
Firing Frequency ◽  
Morphological Features ◽  
Inhibitory Neurons ◽  
Physiological Properties ◽  
Cortical Circuit ◽  
Current Steps ◽  
Constituent Elements ◽  
Whole Cell Recordings

Current dogma holds that a canonical cortical circuit is formed by cellular elements that are basically identical across species. However, detailed and direct comparisons between species of specific elements of this circuit are limited in number. In this study, we compared the morphological and physiological properties of neurogliaform (NGF) inhibitory neurons in the prefrontal cortex (PFC) of macaque monkeys and rats. In both species, NGF cells were readily identified based on their distinctive morphological features. Indeed, monkey NGF cells had only a few morphological features that differed from rat, including a larger soma, a greater number of dendrites, and a more compact axonal field. In contrast, whole cell recordings of the responses to injected current steps revealed important differences between monkey and rat NGF cells. Monkey NGF cells consistently generated a short-latency first spike riding on an initial depolarizing hump, whereas in rat NGF cells, the first spike appeared after a substantial delay riding on a depolarizing ramp not seen in monkey NGF cells. Thus although rat NGF cells are traditionally classified as late-spiking cells, monkey NGF cells did not meet this physiological criterion. In addition, NGF cells in monkey appeared to be more excitable than those in rat because they displayed a higher input resistance, a lower spike threshold, and a higher firing frequency. Finally, NGF cells in monkey showed a more prominent spike-frequency adaptation as compared with rat. Our findings indicate that the canonical cortical circuit differs in at least some aspects of its constituent elements across species.

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