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Synaptic mechanisms of auditory memory

听觉记忆的突触机制

基本信息

批准号：
9651526
负责人：
Stanislav S Zakharenko
金额：
$ 46.05万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9651526
关键词：
5&apos -Nucleotidase Acoustic Stimulation Acoustics Adenosine Adenosine A1 Receptor Adolescent Adult Affect Age Agonist Animals Auditory Auditory area Auditory system Basal Nucleus of Meynert Behavioral Brain Cerebral cortex Cholinergic Receptors Data Dependence Development Discrimination Evaluation Excitatory Synapse Frequencies Funding Future Glutamates Government Individual Kinetics Knock-out Knowledge Language Development Learning Life Long-Term Depression Long-Term Potentiation Maps Mediating Mediator of activation protein Memory Molecular Mus Muscarinic Acetylcholine Receptor Mutant Strains Mice Neocortex Neuromodulator Neurons Organism Perceptual learning Periodicity Persons Presynaptic Terminals Production Property Purinergic P1 Receptors Receptor Activation Receptor Signaling Regulation Rodent Saint Jude Children&apos s Research Hospital Scanning Sensory Signal Transduction Slice Source Stimulus Synapses Synaptic plasticity Testing Thalamic structure Time Training Up-Regulation age related aged auditory thalamus awake cholinergic cortex mapping critical period environmental enrichment for laboratory animals experience experimental study in vivo juvenile animal mature animal mutant neural circuit noradrenergic novel optogenetics overexpression paired stimuli postnatal presynaptic prevent pup response sensory cortex sensory input sound sound frequency

项目摘要

Abstract: Primary sensory cortices analyze sensory information and store information about learned sensory experiences. The auditory cortex (ACx) acquires and retains memory traces about the behavioral significance of selected sounds. During learning, the tuning properties of ACx neurons undergo activity-dependent changes. This cortical map plasticity, which is believed to be a substrate of auditory memory, is characterized by the facilitation of responses to behaviorally important tones. In juvenile animals, cortical map plasticity in the ACx can be induced by passive environmental enrichment with a certain sound. In rodents, juvenile cortical map plasticity is limited to a few postnatal days (i.e., the early critical period). In mature animals, cortical map plasticity can be induced only if tones are behaviorally important or paired with the activation of modulatory (e.g., cholinergic, dopaminergic, noradrenergic) projections. During the previous funding period, we determined that cortical map plasticity is encoded by the same mechanisms as long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical (TC) excitatory synapses. TC projections are the major sensory input to the neocortex and contribute to the formation of cortical maps. In brain slices, we showed that TC synaptic plasticity is not lost after the early critical period, instead a gating mechanism is acquired that can be released by activating cholinergic receptors on presynaptic terminals. Once gating is released, LTP/LTD at TC synapses and cortical map plasticity in vivo occur in animals aged beyond the early critical period. Adenosine machinery, consisting of adenosine-producing ecto-5'-nucleotidase (Nt5e) and A1 adenosine receptors (A1Rs), provides the gating. Juvenile plasticity can be reestablished in adults, if acoustic stimuli are paired with disruption of Nt5e or A1R signaling in the auditory thalamus. This plasticity occurs in cortical maps and individual ACx neurons of awake adult mice and is associated with long-term improvement in tone-discrimination abilities. In this competitive renewal, we propose to test our hypothesis that the adenosine machinery in the thalamus is the master mediator that transmits information from modulatory projections to the thalamus during ACx map plasticity in adults. In Aim 1, we will induce cortical map plasticity in adults by pairing sounds with activation of modulatory projections while activating or deactivating the gating mechanism. In Aim 2, we will explore the molecular mechanisms of terminating the early critical period by investigating age dependency of adenosine production. In Aim 3, we will determine time scales of the gating mechanisms. Using fast-scan cyclic voltammetry in awake mice, we found that adenosine is transiently released in the auditory thalamus and cortex in response to sound. We propose to elucidate the mechanisms and kinetics of this sound-evoked adenosine release before and after the early critical period and determine how it affects spiking in thalamic relay and cortical neurons during sound stimulation. Knowledge gained from these studies will provide the basis for future elucidation of the cellular and molecular mechanisms of auditory memory.

摘要：初级感觉皮层负责分析感觉信息并存储学习到的感觉信息