Abstract
Acetylcholine (ACh) plays an essential role in cortical information processing. Cholinergic changes in cortical state can fundamentally change how the neurons encode sensory input and motor output. Traditionally, ACh distribution in cortex and associated changes in cortical state have been assumed to be spatially diffuse. However, recent studies demonstrate a more spatially inhomogeneous structure of cholinergic projections to cortex. Moreover, many experimental manipulations of ACh have been done at a single spatial location, which inevitably results in spatially non-uniform ACh distribution. Such non-uniform application of ACh across the spatial extent of a cortical microcircuit could have important impacts on how the firing of groups of neurons is coordinated, but this remains largely unknown. Here we describe a method for applying ACh at different spatial locations within a single cortical circuit and measuring the resulting differences in population neural activity. We use two microdialysis probes implanted at opposite ends of a microelectrode array in barrel cortex of anesthetized rats. As a demonstration of the method, we applied ACh or neostigmine in different spatial locations via the microdialysis probes while we concomitantly recorded neural activity at 32 locations with the microelectrode array. First, we show that cholinergic changes in cortical state can vary dramatically depending on where the ACh was applied. Second, we show that cholinergic changes in cortical state can vary dramatically depending on where the state-change is measured. These results suggests that previous work with single-site recordings or single-site ACh application should be interpreted with some caution, since the results could change for different spatial locations.
Highlights
The cerebral cortex is dynamic, exhibiting dramatic changes in population neural activity depending on behavioral context
random eye movement (REM) sleep and the awake state are associated with an asynchronous cortical state, while slow-wave sleep is associated with a synchronized cortical state
Stimulation of basal forebrain tends to result in decreased local field potential (LFP) fluctuations[17] and reduced correlations among spiking neurons in the cortex[4], which suggests that the cholinergic neurons in basal forebrain promote the asynchronous cortical state
Summary
The cerebral cortex is dynamic, exhibiting dramatic changes in population neural activity depending on behavioral context. Direct application of acetylcholine (ACh) agonist carbachol abolishes the slow oscillations of the synchronized state in cortex slices[18]. Both cholinergic projections and changes in cortical state have been assumed to be spatially widespread and diffuse in the cortex. Older studies suggest that ACh distribution varies across cortical layers[20,21,22,23] and within layers (e.g. across whisker barrels in rat somatosensory cortex[23,24]) We require a method that can control ACh in at least two different spatial locations within the same cortical circuit We describe such a method based on two microdialysis probes and a microelectrode array. We show that applying ACh at two different spatial locations results in dramatically different changes in cortical state
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