Probing D2 and 5HT-2A mechanisms in early visual processing in V1

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PROJECT SUMMARY Little is known about the modulatory mechanisms contributed by extra-retinal inputs to primary visual cortex (V1), despite their substantial contribution to visual information processing. While a systematic search across neuromodulators and their receptors is possible, clinical literature provides an avenue to narrow the search of potential receptors contributing to these circuits. Schizophrenia (SZ) is one example, where patients exhibit visual processing deficits. Data suggests these deficits are specific to the magnocellular pathway and not the parvocellular pathway, with shifted contrast sensitivity for sinusoidal grating stimuli at low but not high spatial frequencies and reduced BOLD signal in V1. Magnocellular and parvocellular inputs from the lateral geniculate nucleus of the thalamus are known to show distinct patterns of innervation in V1, but whether there are differences in modulatory mechanisms between these pathways is unknown. Interestingly, there are reports of both typical and atypical antipsychotic medications improving visual deficits in SZ patients. It is known these drugs target a variety of receptors for multiple neuromodulators, providing very little insight into how these drugs may improve symptoms, but showing us that neuromodulation has a profound impact on early visual processing. Research in SZ has emphasized the role of dopamine and serotonin systems, as the early typical antipsychotics show very high affinity for dopamine D2 receptors and drugs with psychedelic effects that may mimic some positive symptoms of SZ target serotonin 5HT-2A receptors. Anatomical studies have reported both receptor types in V1, with clear laminar patterns, though precise localization of these receptors on excitatory or inhibitory neurons remains unknown. Here, we propose to study the role of D2 and 5HT-2A receptors in magnocellular and parvocellular pathways in layer IVC, and in center-surround mechanisms in layers II/III. Aim 1 will test whether magnocellular and parvocellular inputs to V1 show differences in response to activating or blocking dopamine D2 receptors and 5HT-2A receptors. Aim 2a will determine if manipulations to D2 or 5HT-2A receptors impact center-surround mechanisms as a function of stimulus size. Lastly, Aim 2b will determine if there is an effect of D2 or 5-HT2A modulation center-surround mechanism as a function of contrast and orientation.