Modulation of stretch-induced enhancement of neuronal NMDA receptor current by mGluR1 depends upon presence of glia.
Stretching of cultured neurons has been used to model diffuse axonal injury associated with brain trauma. N-Methyl-D-aspartate receptor (NMDAR) activation and group I metabotropic glutamate receptors (mGluRs) are implicated in the pathophysiology of such injury. Here we detail the effects of culture condition and mGluR1 modulation on stretch-enhanced NMDA receptor activity, and show the presence of mGluR1 in addition to mGluR5 in glia. In cortical neurons grown in the absence (PN) or presence (NG) of a glial monolayer, stretch injury (5.7 mm) enhances NMDAR activity by increasing maximal NMDAR current, decreasing the voltage-dependent Mg(2+) block, and altering the kinetic behavior of these receptors. In PN cultures, activation of mGluR1 increases stretch-enhanced NMDAR activity, whereas in NG cultures, such activity is reduced. In contrast, inhibition of mGluR1 in PN cultures limits stretch-enhanced NMDAR activity, whereas in NG cultures activity is increased. MGluR1 modulate stretch-enhanced NMDAR activity through multiple mechanisms including: altering peak or steady state current, affecting Mg(2+) blockade of the NMDAR, or by changing NMDAR kinetics. The presence of glia significantly alters the nature of mGluR1-mediated modulation of NMDAR activity and stretch-induced injury. Together these data indicate a significant neuronal/glial interaction between glial mGluR1 and neuronal NMDA receptor activity.
Lea
Paul M
PM
Department of Neuroscience, Georgetown University, Washington, D.C. 20057-1464, USA.
Custer
Stephanie J
SJ
Stoica
Bogdan A
BA
Faden
Alan I
AI
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology; D016466:CHO Cells; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006224:Cricetinae; D004195:Disease Models, Animal; D015151:Immunoblotting; D008564:Membrane Potentials / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013314:Stress, Mechanical
D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104077:metabotropic glutamate receptor type 1