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Roles of cortical neuromodulation and offline reactivation in memory consolidation of emotionally salient visual experiences

皮质神经调节和离线再激活在情感显着视觉体验的记忆巩固中的作用

基本信息

批准号：
10213293
负责人：
Mark L Andermann
金额：
$ 35万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10213293
关键词：
Address Affect Amygdaloid structure Area Association Learning Axon Behavior Behavioral Biochemical Brain region Calcium Cell physiology Cells Chronic Coupled Cues Cyclic AMP Darkness Data Dendrites Dendritic Spines Discrimination Electrophysiology (science)Emotional Event Food GTP-Binding Proteins Hippocampus (Brain)Image Investigation Joints Lateral Learning Link Medial Methods Molecular Mus Neuromodulator Neuronal Plasticity Neurons Norepinephrine Outcome Pattern Performance Population Rewards Role Second Messenger Systems Sensory Signal Transduction Synapses Synaptic plasticity Task Performances Testing Training Vertebral column Visual association cortex beta-adrenergic receptor classical conditioning cue reactivity experience in vivo learning strategy locus ceruleus structure long term memory memory consolidation memory recall nerve supply neuroregulation noradrenergic optogenetics real time monitoring relating to nervous system response sensory cortex tool two-photon

项目摘要

Summary What are the mechanisms by which we selectively remember sensory cues associated with salient outcomes? Salient sensory experiences activate distributed patterns of neurons in regions including sensory cortex, amygdala, and hippocampus. The linking of neural representations of cues and outcomes is believed to occur both online, during the sensory experiences, and offline, during joint reactivation of cue- and outcome-related patterns of neurons during subsequent quiet periods. Both the online and offline aspects of cue-outcome association learning have been posited to involve co-activation of neuromodulators that project to these distributed brain regions, which may facilitate neural plasticity via actions on intracellular signaling in neuronal dendrites. We have recently developed methods to visualize these network, cellular and subcellular processes across days and weeks in lateral visual association cortex (LVAC) of behaving mice learning an operant Go-NoGo visual discrimination task. LVAC is a key hub that links the hippocampus, sensory cortex, and amygdala. Silencing of either online or offline activity in LVAC perturbs long-term memory consolidation and recall of cue-outcome associations. We previously found that LVAC neuron cue responses are highly plastic across learning and that LVAC is necessary for performance of our task. We showed that the same distinct pattern of neurons that was activated by a given visual cue was subsequently reactivated for ~100-200 ms during quiet waking, with higher reactivation rates during early learning and for salient food- predicting vs. neutral cues. Rates of food-cue but not neutral cue reactivation predicted next-day improvements in performance. Accordingly, reactivations involving ensembles of neurons encoding both the food cue and reward predicted strengthening of next-day functional connectivity of participating neurons, providing a potential cortical substrate for associative learning. This proposal seeks to define the neuromodulatory, signaling, and network mechanisms underlying the above findings, and their causal role in learning. A brain region that densely innervated LVAC and implicated in salience, plasticity, and memory consolidation is the locus coeruleus (LC). Both online and offline LC activity guides which salient experiences are stored. Noradrenaline released by LC neurons can act on beta-adrenergic receptors, thereby boosting cyclic AMP (cAMP), a second messenger that facilitates synaptic plasticity. Thus, we hypothesize that increased neuromodulatory input from LC to LVAC during salient sensory experiences (Aim 1) drives increases in cAMP signaling in LVAC neurons (Aim 2), and biases subsequent offline reactivation of neurons activated during these experiences, in order to modify next-day changes in network activity and behavioral performance (Aims 1-2). We then examine electrophysiological correlates of offline cortical reactivations and their causal role in facilitating network changes and learning (Aim 3). These cellular/subcellular investigations of neural activity and signaling in vivo will address links between neuromodulation, offline reactivation and associative plasticity.

总结