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Cell type-specific mechanisms of history-dependent perceptual biases in sensory cortex

感觉皮层历史依赖性知觉偏差的细胞类型特异性机制

基本信息

批准号：
10739223
负责人：
Deepa L Ramamurthy
金额：
$ 11.17万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739223
关键词：
Acetylcholine Affect Animals Area Arousal Attention Attention deficit hyperactivity disorder Axon Behavior Behavioral Behavioral Model Behavioral Paradigm Behavioral trial Calcium Cells Code Complex Cues Data Detection Disinhibition Environment Exhibits Future Genetic Glutamates Goals Human Image Individual Interneurons Learning Logistic Regressions Maps Mediating Modeling Modernization Monitor Mus Neuromodulator Perception Performance Phase Play Primates Process Pyramidal Cells Recording of previous events Rewards Rodent Role Sensory Shapes Signal Pathway Signal Transduction Somatosensory Cortex Stimulus Techniques Testing Touch sensation Vibrissae attentional bias autism spectrum disorder basal forebrain behavior influence behavior prediction behavioral impairment cell type cholinergic detection sensitivity expectation experience experimental study flexibility insight neural neural circuit neuroregulation novel optogenetics recruit response sensory cortex sensory gating sensory input sensory mechanism sensory stimulus theories tool two-photon

项目摘要

PROJECT SUMMARY Sensory representations are influenced by an animal’s external context, internal state, past experiences, expectations, and future goals. Prior information – including the history of recent stimuli, actions and rewards – plays an important role in guiding ongoing behavior, and can modulate the neural code even at the level of primary sensory cortex. The involvement of sensory cortex in mediating history- dependent shifts in behavior, and the contributions of specific cell types to these effects are not well understood. Using a novel whisker-based behavioral paradigm, I have demonstrated that mice can flexibly and selectively enhance sensory processing of recently rewarded whisker stimuli based on history cues. Here, I propose experiments to uncover the cell type-specific mechanisms in for history-based modulation in primary somatosensory cortex (S1), and test for their causal role in behavior. In Aim 1 (K99), I will use behavioral modeling approaches to systematically quantify history-based perceptual biases during goal-directed behavior in mice. I will examine modulation of pyramidal (PYR) cell activity in S1 of behaving mice while tracking trial-by-trial behavioral shifts in sensory detection performance guided by recent history. I will then empirically test the necessity of S1 in mediating history effects on behavior using reversible inactivation techniques. Two cortical interneuron classes, namely VIP cells and NDNF cells, are widely theorized to play a role in selective enhancement of sensory processing in cortex, since they receive a wide range of glutamatergic and neuromodulatory inputs and boost sensory responses in PYR cells through local disinhibition. Both these cell types are activated in different active behavioral states and learning contexts. In Aim 2 (K99/R00), I will test the role of VIP and NDNF interneurons in gating history-related signals using 2p imaging to monitor their neural activity, and through targeted activation or inactivation of these cell types using optogenetic techniques. VIP and NDNF interneurons are both recruited by acetylcholine, a neuromodulator that is necessary for stimulus-specific enhancement of sensory processing in primates, and behavioral state-based modulation of sensory cortex in rodents. In Aim 3 (R00), I will test the role of basal forebrain cholinergic projections in conveying history-related signals to S1. I will perform two-photon imaging of cholinergic terminals in S1 and use selective optogenetic activation to test whether the locus of prioritized processing on the whiskers can be artificially shifted in behaving mice. Together, the proposed studies will provide new insights into the local cortical circuits that facilitate prioritized processing of behaviorally relevant stimuli in sensory maps.

项目总结