scholarly journals Different composition of glutamate receptors in corticothalamic and lemniscal synaptic responses and their roles in the firing responses of ventrobasal thalamic neurons in juvenile mice

2006 ◽  
Vol 575 (1) ◽  
pp. 161-174 ◽  
Author(s):  
Mariko Miyata ◽  
Keiji Imoto
Keyword(s):  
Glutamate Receptors ◽  
Thalamic Neurons ◽  
Synaptic Responses

Role of Group I Metabotropic Glutamate Receptors in the Patterning of Epileptiform Activities In Vitro

1997 ◽  
Vol 78 (1) ◽  
pp. 539-544 ◽  
Author(s):  
Lisa R. Merlin ◽  
Robert K. S. Wong
Keyword(s):  
Guinea Pig ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group I Mglurs ◽  
Synaptic Responses

Merlin, Lisa R. and Robert K. S. Wong. Role of group I metabotropic glutamate receptors in the patterning of epileptiform activities in vitro. J. Neurophysiol. 78: 539–544, 1997. In guinea pig hippocampal slices, picrotoxin elicited spontaneous epileptiform bursts 300–550 ms in duration. Additional application of ( R,S)-3,5-dihydroxyphenylglycine or ( S)-3-hydroxyphenylglycine, agonists specific for group I metabotropic glutamate receptors(mGluRs), or (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylicacid, a broad-spectrum mGluR agonist, converted picrotoxin-induced interictal bursts into prolonged discharges measured on the order of seconds. The prolonged discharges induced by selective group I mGluR agonist continued to be produced for hours after agonist removal. The antagonists ( S)-4-carboxyphenylglycine and (+)-α-methyl-4-carboxyphenylglycine had no effect on the duration of picrotoxin-induced interictal bursts. However, after agonist exposure, the persistent prolonged discharges occurring in the absence of agonist were reversibly suppressed by the antagonists, suggesting that the activity is maintained via endogenous activation of group I mGluRs by synaptically released glutamate. Our results suggest that, under some conditions, activation of group I mGluRs produces long-lasting enhancement of synaptic responses, mediated at least in part by autopotentiation of the group I mGluR response itself, which may result in the production of seizure discharges and contribute to epileptogenesis.

Physiology and Pharmacology of Corticothalamic Stimulation-Evoked Responses in Rat Somatosensory Thalamic Neurons In Vitro

1997 ◽  
Vol 77 (5) ◽  
pp. 2661-2676 ◽  
Author(s):  
Chang-Qing Kao ◽  
Douglas A. Coulter
Keyword(s):  
Nmda Antagonist ◽  
Excitatory Postsynaptic Potential ◽  
Evoked Responses ◽  
Thalamic Neurons ◽  
Low Frequencies ◽  
Mixed Response ◽  
Postsynaptic Potential ◽  
Synaptic Responses

Kao, Chang-Qing and Douglas A. Coulter. Physiology and pharmacology of corticothalamic stimulation-evoked responses in rat somatosensory thalamic neurons in vitro. J. Neurophysiol. 77: 2661–2676, 1997. Whole cell current- and voltage-clamp recording techniques were employed in a rat thalamocortical slice preparation to characterize corticothalamic stimulation-evoked responses in thalamic neurons. Three types of corticothalamic stimulation-evoked responses were observed in thalamic neurons. Of thalamic neurons, 57% responded to corticothalamic stimulation with purely excitatory synaptic responses, whereas 27% had inhibitory synaptic responses and 16% had mixed excitatory/inhibitory responses. This suggested corticothalamic activation of multiple distinct synaptic circuits, presumably involving both nucleus reticularis thalami (NRT) and thalamus, because the rat ventrobasal complex is virtually devoid of GABAergic interneurons. Corticothalamic-stimulation-evoked excitatory postsynaptic currents (EPSCs) were predominantly slow rising currents that showed nonlinear voltage dependence, characteristics of an N-methyl-d-aspartate (NMDA)-receptor-mediated synaptic current. These slow rising EPSCs were blocked by the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV). A minority of corticothalamic EPSCs had faster kinetics, and were blocked by 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX). Corticothalamic stimulation of varying frequency optimally activated burst responses in thalamic neurons at low frequencies (3–6 Hz). The optimal 3- to 6-Hz response was reduced by ethosuximide, by APV, and by detaching the neocortex from the thalamocortical slice, suggesting that T current, NMDA receptors, and neocortical properties all contributed to generation of this 3- to 6-Hz frequency preference. In contrast to corticothalamic EPSCs, medial-thalamic-stimulation-evoked responses consisted of fast CNQX-sensitive EPSCs that were predominantly voltage insensitive, with no 3- to 6-Hz frequency preference. In thalamic neurons in which corticothalamic stimulation evoked predominantly inhibitory synaptic responses, this inhibitory postsynaptic potential (IPSP) had early and late phases, often followed by a rebound burst. The early IPSP reversed at −95 mV and was bicuculline sensitive, whereas the late IPSP reversed at −113 mV and was blocked by the γ-aminobutyric acid-B (GABAB) antagonist 3- N[1-(S)-(3,4-dic h l o r o p h e n y l ) e t h y l ] a m i n o - 2 - ( S ) - h y d r o x y p r o p y l - P - b e n z y l phoshinic acid (CGP-55845A). In thalamic neurons in which corticothalamic stimulation evoked a mixed excitatory postsynaptic potential (EPSP)/IPSP response, repetitive corticothalamic stimulation rapidly reduced IPSPs and enhanced EPSPs at higher frequencies. This resulted in burst firing being triggered in these mixed response neurons at frequencies >6 Hz. Corticothalamic feedback onto thalamic relay neurons activated diverse responses due to differing relative activation of NRT and “feedforward” inhibitory responses. These multiple in vitro corticothalamic responses differ from responses encountered in other in vitro thalamic preparations lacking a synaptically connected neocortex, but are similar to results evident in thalamic neurons in response to cortical stimulation in vivo. In addition, the thalamocortical 3- to 6-Hz frequency preference was conserved, suggesting that many factors critical for this emergent property of the thalamocortical system are maintained in vitro.

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

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