Acetylcholine contributes through muscarinic receptors to attentional modulation in V1

Abstract

Attention exerts a strong influence over neuronal processing in cortical areas. It selectively increases firing rates and affects tuning properties, including changing receptive field locations and sizes. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.

Figure 1. Drug effects on attentional modulation

a, Attentional enhancement by application of ACh. We recorded the effect of attention on firing rates when no ACh was applied (16 trials) for three bar lengths in the attend-inside receptive field (RF) versus attend-outside (away) condition (box 1). Thereafter we recorded the effect of attention when ACh was applied (16 trials; box 2) followed by recovery (16 trials; box 3). The bottom plot shows the average activity (from 200 ms to 500 ms after stimulus onset) for the different stimulus, attention and drug conditions. ACh increased attentional modulation. b, Effect of scopolamine application on neuronal attentional modulation. All conventions are as in a. Drug application and recovery were repeated three times (boxes 1–6). Scopolamine reduced attentional modulation. Error bars represent s.e.m.

Figure 2. Acetylcholine effects on attentional modulation

a, Quantification of attentional modulation by mean population ROC for different bar length with (black line) or without (red line) ACh application (86 cells; error bars denote s.e.m.). b, Normalized population response depending on ACh application, stimulus (bar length; indicated at the top of each subplot) and attention condition. Activity levels were normalized relative to the peak activity of each neuron and averaged across the population. The red lines indicate activity without ACh application; green lines represent activity with ACh application. The upper line of each colour plot shows the normalized activity when attention was directed to the neuron’s receptive field, the lower line when it was directed away from the receptive field. Widths of the coloured areas show strength of attentional modulation. ACh increased attentional modulation.

Figure 3. Effect of the muscarinic antagonist scopolamine on attentional modulation

a, Quantification of attentional modulation by mean population ROC when scopolamine was (black line) and was not (red line) applied (n = 41 cells, error bars represent s.e.m.). ROC values were significantly reduced on scopolamine application, demonstrating that muscarinic receptors are involved in mediating the effects of attention in V1. b, Normalized population response depending on scopolamine application, bar length (indicated at the top of each subplot) and attention. The widths of the red and green shaded areas show the strengths of attentional modulation as a function of scopolamine application (green lines represent activity with scopolamine application; red lines denote activity without scopolamine application). Attentional modulation was reduced when scopolamine was applied.

Figure 4. Effect of the nicotinic antagonist mecamylamine on attentional modulation

Attentional modulation was quantified by calculating the population ROC for the different bar lengths when mecamylamine was (black line) and was not (grey line) applied (n = 65 cells). ROC values were not significantly affected by mecamylamine application. Error bars show the s.e.m.