Assessing the spatial and temporal scales of attention effects and attention-dependent cholinergic release in macque V4.

Explicitly or implicitly, there are currently three competing models for the role of the neuromodulator acetylcholine
(ACh) in attention. The first asserts that the cholinergic system is spatially imprecise and contributes to a
mechanism for arousal but not attention. The second states that the cholinergic system is spatially imprecise
and is one component of the mechanism for attention. The third states that the cholinergic system is at the center
of the mechanism for attention (implying the system is sufficiently spatially precise to play such a role). In this
study, I will test these three competing models, employing electrochemistry and electrophysiology in the visual
cortex of macaque monkeys performing a cued orientation-change-detection task. If the release of any
neuromodulator is required for the circuit-implementation of attentive effects, the expectation is that the task will
drive release of that molecule into V4, and more specifically that release will occur after presentation of a spatial
cue, and in the vicinity of neurons whose receptive fields (RFs) represent the cued location. The RF of neurons
in visual cortical area V4 will be mapped, then during the task, the cued location will be varied from trial to trial
with respect to this RF location. This will be done, first, at a coarse scale (i.e., attend to the recorded quadrant
or to one of the other three quadrants) and then at a finer scale, attending to different positions along an iso-
eccentricity curve through the RF within the recorded quadrant. Along this iso-eccentricity curve, as the cued
location increasingly overlaps the RF location, the prediction is that there will be a corresponding increase in the
observed effects of attention on spiking activity (e.g., spike rate increases). A custom dual electrochemistry-
electrophysiology recording system will be used to concurrently record both spiking activity and sub-second
changes in local ACh concentration. A measure of the spatial extents of attention-dependent spike rate changes
and attention-dependent ACh release will be derived by plotting these two metrics over stimulus location. These
spatial extent measures (spiking activity changes and ACh concentration changes) will then be compared to rule
in or out each of the three competing models for the role of ACh in attention. In addition to offering the first
rigorous test of the hypothesis that ACh release supports attention, this study will provide the first measurements
of the concentration, timing, and spatial extent of ACh release during an attention task in a primate.

Grant Number: 5F31EY035522-03
NIH Institute/Center: NIH
Principal Investigator: John Amodeo