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

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.

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β1- and β2-Adrenergic activations enhance excitatory synaptic transmission in layer V/VI pyramidal neurons of the medial prefrontal cortex of rats

Neuroscience Research ◽

10.1016/j.neures.2010.07.1989 ◽

2010 ◽

Vol 68 ◽

pp. e449

Author(s):

Zejun Feng

Keyword(s):

Prefrontal Cortex ◽

Synaptic Transmission ◽

Medial Prefrontal Cortex ◽

Pyramidal Neurons ◽

Excitatory Synaptic Transmission ◽

Layer V

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Curcumin inhibits glutamate release in nerve terminals from rat prefrontal cortex: Possible relevance to its antidepressant mechanism

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2011.06.012 ◽

2011 ◽

Vol 35 (7) ◽

pp. 1785-1793 ◽

Cited By ~ 41

Author(s):

Tzu Yu Lin ◽

Cheng Wei Lu ◽

Chia-Chuan Wang ◽

Ying-Chou Wang ◽

Su-Jane Wang

Keyword(s):

Prefrontal Cortex ◽

Glutamate Release ◽

Nerve Terminals

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Activation of Presynaptic Group III Metabotropic Receptors Enhances Glutamate Release in Rat Entorhinal Cortex

Journal of Neurophysiology ◽

10.1152/jn.2000.83.5.2519 ◽

2000 ◽

Vol 83 (5) ◽

pp. 2519-2525 ◽

Cited By ~ 27

Author(s):

D. Ieuan Evans ◽

Roland S. G. Jones ◽

Gavin Woodhall

Keyword(s):

Synaptic Transmission ◽

Entorhinal Cortex ◽

Metabotropic Glutamate Receptors ◽

Glutamate Release ◽

Facilitatory Effect ◽

Metabotropic Receptors ◽

Patch Clamp Technique ◽

Group Iii ◽

Bath Application ◽

Layer V

The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 μM) resulted in a marked facilitation of both spontaneous and activity-independent “miniature” (s/mEPSC) event frequency. The facilitatory effect of L-AP4 (100 μM) on sEPSC frequency prevailed in the presence ofdl−2-amino-5-phosphonopentanoic acid (100 μM) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 μM). These data confirmed that group III mGluRs, and not N-methyl-d-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (20 μM) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.

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Layer V neurons bear the majority of mRNAs encoding the five distinct dopamine receptor subtypes in the primate prefrontal cortex

Synapse ◽

10.1002/(sici)1098-2396(199801)28:1<10::aid-syn2>3.0.co;2-f ◽

1998 ◽

Vol 28 (1) ◽

pp. 10-20 ◽

Cited By ~ 72

Author(s):

Michael S. Lidow ◽

Feng Wang ◽

Yang Cao ◽

Patricia S. Goldman-Rakic

Keyword(s):

Prefrontal Cortex ◽

Dopamine Receptor ◽

Receptor Subtypes ◽

Dopamine Receptor Subtypes ◽

Layer V

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The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa074 ◽

2020 ◽

Vol 46 (6) ◽

pp. 1471-1481 ◽

Cited By ~ 2

Author(s):

Martina Ulivieri ◽

Joanna Monika Wierońska ◽

Luana Lionetto ◽

Katiuscia Martinello ◽

Paulina Cieslik ◽

...

Keyword(s):

Prefrontal Cortex ◽

Metabotropic Glutamate Receptors ◽

Systemic Treatment ◽

Glutamate Release ◽

Ultra Performance Liquid Chromatography ◽

Human Brain Tissue ◽

Metabotropic Glutamate ◽

Chromatography Tandem Mass Spectrometry ◽

Highly Sensitive ◽

Liquid Chromatography Tandem Mass

Abstract Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using a highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found that CA is present in trace amounts in human brain tissue. CA levels were largely reduced in the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication and might, therefore, represent a trait of schizophrenia. Interestingly, systemic treatment with low doses of CA (<1 mg/kg, i.p.) showed robust efficacy in several behavioral tests useful to study antipsychotic-like activity in mice and rats and attenuated MK-801-evoked glutamate release. CA failed to display antipsychotic-like activity and inhibit excitatory synaptic transmission in mice lacking mGlu4 receptors. These findings suggest that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.

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The functional influence of nicotinic cholinergic receptors on the visual responses of neurones in the superficial superior colliculus

Visual Neuroscience ◽

10.1017/s0952523800172116 ◽

2000 ◽

Vol 17 (2) ◽

pp. 283-289 ◽

Cited By ~ 30

Author(s):

K.E. BINNS ◽

T.E. SALT

Keyword(s):

Superior Colliculus ◽

Nicotinic Receptors ◽

Visual Stimulation ◽

Glutamate Release ◽

Drug Application ◽

Receptor Activation ◽

Visual Input ◽

Visual Response ◽

Visual Responses ◽

Parabigeminal Nucleus

In the rat, the superficial gray layer (SGS) of the superior colliculus receives glutamatergic projections from the contralateral retina and from the visual cortex. A few fibers from the ipsilateral retina also directly innervate the SGS, but most of the ipsilateral visual input is provided by cholinergic afferents from the opposing parabigeminal nucleus (PBG). Thus, visual input carried by cholinergic afferents may have a functional influence on the responses of SGS neurones. When single neuronal extracellular recording and iontophoretic drug application were employed to examine this possibility, cholinergic agonists were found to depress responses to visual stimulation. Lobeline and 1-acetyl-4-methylpiperazine both depressed visually evoked activity and had a tendency to reduce the background firing rate of the neurones. Carbachol depressed the visual responses without any significant effect on the ongoing activity, while the muscarinic receptor selective agonist methacholine increased the background activity of the neurones and reduced their visual responses. Lobeline was chosen for further studies on the role of nicotinic receptors in SGS. Given that nicotinic receptors are associated with retinal terminals in SGS, and that the activation of presynaptic nicotinic receptors normally facilitates transmitter release (in this case glutamate release), the depressant effects of nicotinic agonists are intriguing. However, many retinal afferents contact inhibitory neurones in SGS; thus it is possible that the increase in glutamate release in turn facilitates the liberation of GABA which goes on to inhibit the visual responses. We therefore attempted to reverse the effects of lobeline with GABA receptor antagonists. The depressant effects of lobeline on the visual response could not be reversed by the GABAA antagonist bicuculline, but the GABAB antagonist CGP 35348 reduced the effects of lobeline. We hypothesize that cholinergic drive from the parabigeminal nucleus may activate presynaptic nicotinic receptors on retinal terminals, thereby facilitating the release of glutamate onto inhibitory neurones. Consequently GABA is released, activating GABAB receptors, and thus the ultimate effect of nicotinic receptor activation is to depress visual responses.

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