Different glutamate receptors convey feedforward and recurrent processing in macaque V1

Abstract

Neurons in the primary visual cortex (V1) receive feedforward input from the thalamus, which shapes receptive-field properties. They additionally receive recurrent inputs via horizontal connections within V1 and feedback from higher visual areas that are thought to be important for conscious visual perception. Here, we investigated what roles different glutamate receptors play in conveying feedforward and recurrent inputs in macaque V1. As a measure of recurrent processing, we used figure-ground modulation (FGM), the increased activity of neurons representing figures compared with background, which depends on feedback from higher areas. We found that feedforward-driven activity was strongly reduced by the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas this drug had no effect on FGM. In contrast, blockers of the NMDA receptor reduced FGM, whereas their effect on visually driven activity varied with the subunit specificity of the drug. The NMDA receptor blocker 2-amino-5-phosphonovalerate (APV) caused a slight reduction of the visual response, whereas ifenprodil, which targets NMDA receptors containing the NMDA receptor NR2B subunit, increased the visual response. These findings demonstrate that glutamate receptors contribute differently to feedforward and recurrent processing in V1 and suggest ways to selectively disrupt recurrent processing so that its role in visual perception can be elucidated.

Fig. 1.

Behavioral task and recording method. (A) Example of a figure–ground texture with a figure composed of 135°-oriented lines on a background of lines oriented at 45°. The red circle in the center of the display is the fixation point. (B) Schematic representation of the main conditions with the multiunit RF inside or outside the figure. In the ground condition, the figure was placed at one of two possible locations at an angle of 120° from the RF position, at the same eccentricity. The task of the monkey was to make a saccade into a target window centered on the figure, after the fixation point was extinguished.

Fig. 2.

Example drug effects on neuronal activity in area V1. (A) Multiunit neuronal responses at an electrode situated in the superficial layers before and after the injection of 40 nL of APV. Thick and thin traces show MUAe responses evoked by the figure and background, respectively, and the shaded regions indicate the FGM. The data shown here were normalized by the maximum response across conditions in the predrug period. The data from the recovery period were obtained 1 h after the injection. The bar graphs on the right show the effect of the drug on the peak response, which was defined as the average activity evoked by figure and background from 50 to 100 ms after stimulus onset (upper graph) and on FGM, which was defined as the difference between the response evoked by figure and background in a window from 100 to 200 ms after stimulus onset. The error bars show the SEM. (B) Effects of a 30-nL injection of ifenprodil at a layer 4 electrode that caused an increase in peak response and a decrease in FGM that did not recover, although the session was continued for 1.5 h postinjection. (C) Example of a 30-nL injection of CNQX that produced a decrease in the peak response but did not reduce FGM; the electrode was situated in the superficial layers. The data from the recovery epoch were recorded more than 90 min after the injection.

Fig. 3.

Drug effects on visual responsivity across recording sites. (A) Average change in overall response (from 0 to 200 ms after stimulus onset, averaged across figure and ground conditions) across all recording sites after injections of APV (blue), ifenprodil (green), CNQX (red), and aCSF (black). The graph shows the change in response compared with the predrug baseline. (Negative numbers indicate a decrease in response.) Yellow bars indicate the response in the recovery epoch. Error bars denote SEM across recording sites. (B) Effect of the different drugs on the activity during the peak response window (50–100 ms after stimulus onset) for the figure (squares), ground (circles), and catch trials (triangles). The predrug activity has been subtracted, and negative values, therefore, indicate that the drug reduced the response. The effects of the drugs on the responses evoked by the figure and background were identical in this time window. (C) Change in response during the modulation period (100–200 ms after stimulus onset). The difference between the effect of the drugs on activity evoked by the figure and ground corresponds to the drug effect on FGM (reported in Fig. 4A). ***P < 0.001 (paired t test).

Fig. 4.

Drug effects on figure–ground modulation. (A) Average change in FGM (in a window from 100 to 200 ms after stimulus onset) across all recording sites after injections of APV (blue), ifenprodil (green), CNQX (red), and aCSF (black). Negative numbers indicate a decrease in FGM. Yellow bars indicate FGM in the recovery epoch, and error bars denote SEM across recording sites. (B) Change in MI caused by the drugs. (C) Effects of APV on FGM per penetration. x axis, average predrug FGM across recording sites of one penetration; y axis, postdrug FGM. Error bars show SEM. Penetrations with a nonsignificant effect may have been the result of failed injections. (D) Effect of ifenprodil across penetrations.