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

项目总结 视网膜外输入对初级视皮层的调节机制知之甚少。 (V1)，尽管它们对视觉信息处理作出了重大贡献。在系统的搜索过程中 神经调节剂及其受体是可能的，临床文献提供了缩小研究范围的途径 参与这些回路的潜在受体。精神分裂症(SZ)就是一个例子，患者表现出 视觉处理缺陷。数据表明，这些缺陷是大细胞途径特有的，而不是 微小细胞通路，在低空间但不高空间对正弦光栅刺激具有偏移的对比敏感度 V1中的频率和减少的粗体信号。来自外侧的大细胞和小细胞输入 已知丘脑膝状核在V1显示出不同的神经支配模式，但是否有 这些通路之间的调控机制是否存在差异尚不清楚。有趣的是，这里有 关于典型和非典型抗精神病药物改善SZ患者视力障碍的报道。它是 已知这些药物针对多种神经调节剂的各种受体，对 这些药物可能如何改善症状，但向我们展示了神经调节对早期 视觉处理。深圳的研究强调了多巴胺和5-羟色胺系统的作用，因为早期 典型的抗精神病药物对多巴胺D2受体和具有迷幻作用的药物显示出非常高的亲和力 可能与SZ靶向5-羟色胺-2A型受体的某些阳性症状相似。解剖学研究已经 报道了V1中的两种受体类型，具有明显的层状模式，尽管这些受体的精确定位 对兴奋性或抑制性神经元的影响尚不清楚。在这里，我们建议研究D2和5HT-2A的作用 下腔静脉层巨细胞和小细胞通路中的受体，以及中枢-周围机制 第二层/第三层。Aim 1将测试V1的大细胞和小细胞输入是否表现出不同的反应 激活或阻断多巴胺D2受体和5-羟色胺-2A受体。目标2a将确定操控 D2或5-羟色胺-2A受体影响中枢-周围机制，作为刺激大小的函数。最后，目标2b 将确定是否存在作为以下函数的D2或5-HT2a调制中心环绕机制的影响 对比度和方向性。

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.