Glycine at the NMDA receptor in cat visual cortex: saturation and changes with age

1996 ◽  
Vol 75 (1) ◽  
pp. 311-317 ◽  
Author(s):  
D. Czepita ◽  
N. W. Daw ◽  
S. N. Reid
Keyword(s):  
Visual Cortex ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Visual Response ◽  
Glycine Site ◽  
Positive Evidence ◽  
Cat Visual Cortex ◽  
Site Of Action

1. Saturation of the glycine site at the N-methyl-D-aspartate (NMDA) receptor in cat visual cortex was tested by iontophoresing D-serine, and the contribution of this site to the visual response was tested by iontophoresing 7-chlorokynurenic acid (7-Cl-KYNA). Animals were tested at ages 3 wk, 6 wk, 5 mo, and adult. 2. In at least 40% of cells (24/57), D-serine increased the response significantly, showing that the glycine site was not saturated. However, the increase was rarely > 100%. 3. The amount by which D-serine increased the response did not vary significantly with age. 4. In five cases there was positive evidence for saturation of the glycine site. D-Serine did not increase the response significantly; however, when D-serine was applied on top of 7-Cl-KYNA, it did increase the response compared with that seen with 7-Cl-KYNA alone. These cases were all in 3-wk-old animals. In other cases (28/57), D-serine did not increase the response significantly, but we could not be absolutely certain that the D-serine had reached the site of action. 5. The effect of 7-Cl-KYNA was largest in 3-wk animals, in agreement with previous findings that the effect of D-2-amino-5-phosphonovalerate (APV) is largest at this age. 6. These results may provide a small part of the explanation for the finding that the NMDA receptor-mediated component of the visual response decreases between 3 and 6 wk of age, while the number of NMDA receptors is increasing. However, the magnitude of the results make it likely that other factors are more important.

The effect of varying stimulus intensity on NMDA-receptor activity in cat visual cortex

1990 ◽  
Vol 64 (5) ◽  
pp. 1413-1428 ◽  
Author(s):  
K. Fox ◽  
H. Sato ◽  
N. Daw
Keyword(s):  
Visual Cortex ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Activation ◽  
Visual Response ◽  
Background Luminance ◽  
Stimulus Contrast ◽  
Cat Visual Cortex ◽  
Low Levels ◽  
Nmda Receptor Activation

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)

A Model for the Action of NMDA Conductances in the Visual Cortex

1992 ◽  
Vol 4 (1) ◽  
pp. 59-83 ◽  
Author(s):  
Kevin Fox ◽  
Nigel Daw
Keyword(s):  
Visual Cortex ◽  
Steady State ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Excitatory Amino Acid ◽  
Membrane Conductance ◽  
Hill Coefficient ◽  
Visual Response ◽  
State Equations ◽  
Response Curves

A model is presented for the behavior of N-methyl-D-aspartate (NMDA) receptors during neuronal responses to visual stimuli in visual cortex based on classical steady-state equations for membrane conductance, and for binding of transmitter with NMDA and non-NMDA receptors. Constraints in the equations and the equation for voltage dependency of the NMDA receptors come from measurements in hippocampus, embryonic CNS neurons, and cortex. An excitatory amino acid transmitter released from terminals in the visual cortex is assumed to be related to the contrast of the stimulus by a hyperbolic tangent formula. The transmitter is assumed to be glutamate. The model is a two compartment representation of a single neuron at steady state. The model fits results obtained from contrast-response curves measured in the visual cortex in control conditions and with iontophoresis of NMDA and non-NMDA agonists or antagonists. The model shows how NMDA receptors contribute to the visual response in a graded multiplicative fashion at all levels of contrast. NMDA receptors do not show switch behavior, that is, they are not turned on at high levels of stimulation only. The difference in NMDA receptor current between low and high levels of stimulation cannot be accounted for solely by the voltage dependency of the NMDA receptor. One needs, in addition, another factor, such as a difference in the Hill coefficient for binding of glutamate at the NMDA receptor.

Effect of longer periods of dark rearing on NMDA receptors in cat visual cortex

1994 ◽  
Vol 72 (3) ◽  
pp. 1220-1226 ◽  
Author(s):  
D. Czepita ◽  
S. N. Reid ◽  
N. W. Daw
Keyword(s):  
Visual Cortex ◽  
Nmda Receptor ◽  
Firing Rate ◽  
Spontaneous Activity ◽  
Visual Response ◽  
Visual Responses ◽  
Level Of Activity ◽  
Direction Of Movement ◽  
Excitatory Drive ◽  
Dark Rearing

1. Cats were reared in the dark to 3, 5, and 11 mo. We studied the N-methyl-D-aspartate (NMDA) receptor contribution to the visual response in the cortex, defined as the percentage reduction in visual response after application of 2-amino-5-phosphonovaleric acid (APV). We also studied the firing rate in response to the optimal visual stimulus and the spontaneous activity. We made comparisons of all these properties between light-reared and dark-reared animals. 2. The NMDA receptor contribution to the visual response in layers IV, V, and VI of dark-reared animals was substantially above that in light-reared animals at all ages tested. 3. The specificity of receptive field properties in dark-reared animals showed some degeneration between 6 wk and 3 mo of age. At > or = 3 mo, almost no cells were specific for orientation and direction of movement. 4. Firing rate was lower in dark-reared animals at all ages, suggesting a decrease in excitatory drive to the visual cortex. 5. Spontaneous activity was equal in dark- and light-reared animals, suggesting that the overall level of activity (including visual responses as well as spontaneous activity) in light-reared animals is higher than in dark-reared animals. This should tend to upregulate glutamate receptors in general in dark-reared animals.

Dependence of retinogeniculate transmission in cat on NMDA receptors

1990 ◽  
Vol 63 (2) ◽  
pp. 347-355 ◽  
Author(s):  
A. M. Sillito ◽  
P. C. Murphy ◽  
T. E. Salt ◽  
C. I. Moody
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Visual Response ◽  
Visual Responses ◽  
Receptor Agonists ◽  
Selective Blockade ◽  
X And Y Cells ◽  
X 24 ◽  
Y Cells

1. We have examined the possibility that N-methyl-D-aspartate (NMDA) receptors may be involved in the visual response of relay cells in the cat dorsal lateral geniculate nucleus (dLGN). The selective NMDA receptor antagonists D-2-amino-5-phosphonovalerate (APV) and 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) have been iontophoretically applied to X and Y cells in the dLGN and their effects on the visual response to a light spot flashed within the receptive field center determined. 2. The antagonist effects were assessed at ejection current levels producing a selective blockade of the responses to iontophoretically applied NMDA with respect to those elicited by the non-NMDA receptor agonists quisqualate and kainate. These selective effects were determined in an experimental paradigm where the visual response and responses to NMDA and the non-NMDA receptor agonists were compared in the same test run. The data refer to a total population of 52 cells (28 X, 24 Y). 3. Application of APV abolished or greatly reduced the visual responses of both X and Y cells. The mean percentage reduction in the visual response for the X cells studied was 59 +/- 10% (SE; n = 7) and for the Y cells 66 +/- 8% (SE; n = 11). Both the early onset transient and the sustained component of the visual response to the flashed stimulus were equally affected. 4. The antagonist CPP produced a similar pattern of effect to APV, substantially reducing or abolishing the visual response in both X and Y cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotransmitter receptors mediating excitatory input to cells in the cat lateral geniculate nucleus. I. Lagged cells

1990 ◽  
Vol 63 (6) ◽  
pp. 1347-1360 ◽  
Author(s):  
P. Heggelund ◽  
E. Hartveit
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Lateral Geniculate Nucleus ◽  
Transient Response ◽  
Visual Response ◽  
Response Component ◽  
Gaba Antagonists ◽  
Gaba A ◽  
Lagged Cells

1. Synaptic mechanisms that might explain the functional properties of the recently discovered class of lagged cells in the dorsal lateral geniculate nucleus (LGN) were analyzed with electrophysiological and pharmacologic techniques. To study the type of excitatory amino acid (EAA) receptor that mediates visual responses of lagged cells, we recorded the response of single cells to a stationary flashing light spot before, during, and after microiontophoretic application of antagonists and agonists to EAA receptors. 2. The visual response of the lagged cells could be almost completely blocked by an antagonist to the N-methyl-D-aspartate (NMDA) receptor. The degree of suppression was dose dependent, and the average maximum degree of suppression for all the cells was 94%. NMDA enhanced the response, and this enhancement was antagonized by NMDA antagonists. A quisqualate/kainate receptor antagonist had no significant effect on the lagged cells. 3. These findings indicate that the visual response in lagged cells is dependent upon activation of NMDA receptors, which may directly result from activation of retinal inputs. 4. No pharmacologic difference was seen between lagged X- and Y-cells, or between lagged ON- and OFF-center cells. 5. gamma-Aminobutyric acid-A (GABA-A) receptor antagonists were used to study whether the characteristic lag of the visual response and the suppression of the initial transient response component of the lagged cells are dependent on geniculate inhibition. Beside enhancement of the visual response, the GABA antagonists strongly reduced the lag of the visual response, and an initial transient response component occurred instead of the initial suppression. The lag remained slightly longer than for nonlagged cells, and the peak firing rate of the transient was below values typical for nonlagged cells, indicating that the lagged cell properties are dependent on other factors beside GABA-A receptor-mediated inhibition. 6. The enhanced visual response during iontophoresis of GABA antagonists could be completely blocked by simultaneous iontophoresis of an NMDA-receptor antagonist. This gives further support to the hypothesis that the retinal input to these cells is mediated by NMDA receptors. 7. The NMDA-receptor/ionophore complex mediates excitatory postsynaptic potentials (EPSPs) characterized by slow rise and decay times and long duration. The ionophore is characterized by a voltage-dependent blockade that makes these receptors particularly sensitive to inhibitory input. The temporal interplay between the slow NMDA receptor-mediated EPSPs and the fast GABA receptor-mediated inhibitory postsynaptic potentials (IPSPs) may explain the characteristic response properties of the lagged cells.

Effect of the Group I Metabotropic Glutamate Agonist DHPG on the Visual Cortex

2001 ◽  
Vol 86 (4) ◽  
pp. 1622-1631 ◽  
Author(s):  
Xiao-Tao Jin ◽  
Christopher J. Beaver ◽  
Qinghua Ji ◽  
Nigel W. Daw
Keyword(s):  
Visual Cortex ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Visual Response ◽  
Excitatory Effect ◽  
Partial Explanation ◽  
Metabotropic Glutamate ◽  
Cat Visual Cortex ◽  
Group I

Metabotropic glutamate receptors have a variety of effects in visual cortex that depend on the age of the animal, the layer of the cortex, and the group of the receptor. Here we describe these effects for group I receptors, using both in vivo and in vitro preparations. The metabotropic group I glutamate receptor agonist 3,5 dihydroxyphenylglycine (DHPG) potentiates the responses to N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in slices of rat visual cortex. It also increases, initially, the visual response in the cat visual cortex. Both these effects are largest at 3–4 wk of age and decline to insignificance by 10 wk of age. Both are also largest in lower layers of cortex, which explains why the facilitatory effects found with the general metabotropic glutamate agonist 1S,3R aminocyclopentane-1,3-dicarboxylic acid (ACPD) are observed only in lower layers. Prolonged application of DHPG in the cat visual cortex, after the initial excitatory effect, produces depression. We also found that DHPG facilitates the NMDA response in fast-spiking cells, which are inhibitory, providing a partial explanation for this. Thus there are multiple effects of group I metabotropic glutamate receptors, which vary with layer and age in visual cortex.

Activation of metabotropic glutamate receptors has different effects in different layers of cat visual cortex

1997 ◽  
Vol 14 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Silvia N.M. Reid ◽  
Nigel W. Daw
Keyword(s):  
Visual Cortex ◽  
Dicarboxylic Acid ◽  
Glutamate Receptors ◽  
Spontaneous Activity ◽  
Primary Visual Cortex ◽  
Metabotropic Glutamate Receptors ◽  
Visual Response ◽  
Single Neurons ◽  
Metabotropic Glutamate ◽  
Cat Visual Cortex

AbstractSingle neurons were recorded in cat primary visual cortex, and the effect of iontophoresis of the metabotropic glutamate agonist 1S,3R-aminocyclopentane-1.3-dicarboxylic acid (ACPD) was observed. In nearly all cases (41/43), ACPD reduced the visual response. In some cases ACPD also reduced spontaneous activity (24/43), and in other cases ACPD increased spontaneous activity (18/43). Increases were generally seen in infragranular layers (V and VI), and decreases in supragranular layers (II and III). The reduction in the visual response was also largest in supragranular layers. We conclude that activation of metabotropic glutamate receptors has both facilitatory and depressive effects in visual cortex, and the effect depends on the layer of the cell recorded.

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