Cholinergic manipulations affect sensory responses but not attentional enhancement in macaque MT

Abstract

Background: Attentional modulation in the visual cortex of primates is characterized by multiplicative changes of sensory responses with changes in the attentional state of the animal. The cholinergic system has been linked to such gain changes in V1. Here, we aim to determine if a similar link exists in macaque area MT. While rhesus monkeys performed a top-down spatial attention task, we locally injected a cholinergic agonist or antagonist and recorded single-cell activity.

Results: Although we confirmed cholinergic influences on sensory responses, there was no additional cholinergic effect on the attentional gain changes. Neither a muscarinic blockage nor a local increase in acetylcholine led to a significant change in the magnitude of spatial attention effects on firing rates.

Conclusions: This suggests that the cellular mechanisms of attentional modulation in the extrastriate cortex cannot be directly inferred from those in the primary visual cortex.

Fig. 1

a Schematic trial structure of the spatial attention task. The three attention conditions, attend-fix, attend-in, and attend-out, were shown in random order. In the attend-fix trials, the monkey had to respond to a luminance change of the centrally presented fixation point. In attend-in and attend-out trials, the monkey had to respond to a direction change of the cued dot pattern. ISI inter-stimulus interval. b Experimental design. One full cycle of the main experiment consists of control, injection, and recovery blocks. Injection and recovery could be performed several times during one experiment. The black horizontal bar depicts the assignment of trials to the control block. The light gray horizontal bar depicts the assignment of trials to the injection block. The depicted concentration of the substance is speculative

Fig. 2

a Effect of spatial attention on neuronal firing rate across trial time course for monkey P (average AMI 0.094, i.e., 20.7%). Peristimulus time histograms were calculated for the control block for the scopolamine cell population of each monkey separately for the three attentional conditions. The analysis period (used to determine the AMI) is defined as 300–800 ms after RDP onset (gray shaded area). The initial firing rate modulation in the attend-in condition is due to the cue, which was present in the receptive field only during the attend-in condition. b Effect of spatial attention on neuronal firing rate across trial time course for monkey O (average AMI 0.047, i.e., 9.9%). c, d Effect of spatial attention on example MT cells (c s1-pie-035-01+01_2a, d s3-pie-020-01+02_1a), both of which showed a significant effect of scopolamine injection on firing rates in the fixation condition

Fig. 3

a PSTH of full scopolamine population of two monkeys showing neuronal spiking dynamics for the three attentional conditions during control block (solid lines, composed of the data shown in Fig. 2a and b) and injection block (dashed lines). b Distribution of injection modulation indices (IMI) for the sensory condition (attend-fix). Light gray depicts the full population fulfilling the first inclusion criterion, and dark gray depicts the subpopulation of cells with significant influence of injection on their firing rate. The red vertical dashed line indicates the median injection modulation for the full population. Shown data contains neuronal responses of single units from two monkeys for the preferred stimulus only. c, d Histogram of attentional modulation index for control (upper histograms) and scopolamine injection blocks (lower histograms) for cells showing a significant decrease (c) or increase (d) in firing rate at the single-cell level due to scopolamine injection. Paired differences are illustrated in insets. Red vertical dashed lines indicate the median change of the population

Fig. 4

a PSTH of full acetylcholine population of two monkeys showing neuronal spiking dynamics for the three attentional conditions (attend-in: red, attend-out: blue, fixation: light blue) during control block (solid line) and injection block (dashed line). b Distribution of injection modulation indices (IMI) for the sensory condition. Light gray depicts the full population fulfilling the first inclusion criteria, and dark gray depicts a subpopulation of cells with significant influence of injection on their firing rate during the fixation condition. Red vertical dashed line indicates median injection modulation for the full population. Shown data is derived from neuronal responses of single units from two monkeys for the preferred stimulus only. c, d Distribution of attentional modulation index (AMI) for control and acetylcholine injection block of the significantly affected cells, showing a decrease (c) or an increase (d) in firing rate. Red vertical dashed lines indicate median attentional modulation