The effect of varying stimulus intensity on NMDA-receptor activity in cat visual cortex.
1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the visual responses of cells in different layers of the cat visual cortex at different levels of excitatory drive (which was varied by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells in area 17 of cat cortex. Cells were characterized to determine the optimal visual stimulus, the brightness of which was then varied relative to background luminance to construct a contrast-response (C-R) curve for each cell. Curves were made during control conditions and during application of agonists (NMDA and quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid components of the visual response. 3. Threshold responses were obtained with stimuli between 1/60 and 1.8 X background luminance. The cell response, measured by firing rate, was linearly related to stimulus contrast over 1-2 decades and saturated at higher contrasts. 4. Application of APV reduced the slope of the linear portion of the C-R curve for cells located in layers II and III (average reduction, 59% of control). APV did not decrease the threshold to stimulation. The "just suprathreshold" responses to stimulation were reduced by the same proportion as the saturation responses for individual cells. The principal effect was therefore to reduce the gain of the C-R curve in these layers. 5. Application of APV reduced the spontaneous activity of cells located in layers IV, V, and VI with little if any effect on the gain of the C-R curve. This suggests a tonic background level of NMDA-receptor activation in these layers, which is not directly related to the visual response. 6. Low levels of NMDA increased the gain of the C-R curve in layers II/III and V/VI. On the other hand, low levels of quisqualate increased the overall level of firing without affecting the gain of the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These experiments show that visual stimuli that produce just suprathreshold responses activate NMDA receptors. The degree of activation is proportionally the same for small responses and large responses for an individual cell. Rather than finding a threshold for NMDA-receptor activation, a continuous range of NMDA-receptor influence was observed over the entire response range.(ABSTRACT TRUNCATED AT 250 WORDS)
Fox
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Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Sato
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Daw
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D004566:Electrodes; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007478:Iontophoresis; D009474:Neurons / Q000502:physiology; D010775:Photic Stimulation; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D014793:Visual Cortex / Q000502:physiology*
D000596:Amino Acids; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; C031231:2-amino-7-phosphonoheptanoic acid