Cholinergic Modulation of Visual Cortical Processing

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DESCRIPTION (provided by applicant): The cholinergic system of basal forebrain (nucleus basalis, NB) has been implicated in important cognitive functions such as arousal, attention, and memory, yet little is known of how this system affects cortical processing. Previous studies have shown that NB stimulation causes bi-directional changes in the overall firing rate of cortical neurons. Additionally, the laminar distributions of different subtypes of acetylcholine (ACh) receptors suggest that ACh can selectively boost feedforward thalamocortical inputs while suppressing recurrent intracortical interactions. Thus, although cortical cholinergic input does not carry sensory information, it may act to modulate neural excitability and effective connectivity in the cortex. These changes in the cortical circuit may in turn affect visual processing by dynamically altering cortical receptive field (RF) properties. I have generated a series of hypotheses on the effect of NB stimulation on visual cortical RFs. In the proposed project, I will test these hypotheses by stimulating the NB while making multielectrode recordings from neurons in the adult rat visual cortex. Specifically, I will characterize the effects of NB stimulation on (i) V1 orientation tuning, direction selectivity, and spatiotemporal receptive field (STRF) properties (ii) spatial phase sensitivity of visual responses (which differs between simple and complex cells), and (iii) response characteristics to natural scenes. Determining the effects of NB stimulation on cortical RFs will provide important insights into the modulation of ongoing sensory processing that potentially underlies higher-level cognitive processes. PUBLIC HEALTH RELEVANCE Nucleus Basalis is one of the first and most severely damaged areas affected by Alzheimer's disease. Thus, understanding what effect it has on sensory processing represents an important step in understanding the pathologies associated with Alzheimer's disease. The proposed research will elucidate the receptor types involved in specific changes to sensory processing as well as suggest potential treatment strategies using pharmacological agents.