Synaptic mechanisms of auditory memory

摘要：初级感觉皮层分析感觉信息并存储有关学习到的感觉的信息 经历。听觉皮质(ACX)获取并保留有关行为意义的记忆痕迹 选定的声音。在学习过程中，ACX神经元的调谐特性经历活动依赖 改变。这种大脑皮层的可塑性被认为是听觉记忆的底物，其特征是 通过促进对行为上重要的音调的反应。在幼年动物中，大脑皮质图的可塑性 ACX可以由一定声音的被动环境富集物诱导。啮齿动物幼年皮质 MAP的可塑性仅限于出生后几天(即早期关键期)。在成熟动物中，大脑皮层地图 只有当音调是行为上重要的或与调节的激活配对时，才能诱导可塑性 (如胆碱能、多巴胺能、去甲肾上腺素能)投射。在上一个资助期内，我们决定 大脑皮层MAP可塑性由与长时程增强(LTP)和长时程增强(LTP)相同的机制编码 丘脑皮质兴奋性突触抑制(LTD)。TC投射是主要的感官输入 并有助于大脑皮层地图的形成。在脑片上，我们发现TC突触 在早期的临界期之后，塑性并没有丧失，相反，获得了可以释放的门控机制 通过激活突触前终末上的胆碱能受体。一旦门控被释放，TC突触的LTP/LTD 而体内皮质MAP的可塑性发生在超过早期临界期的动物身上。腺苷机械， 由产生腺苷的胞外-5‘-核苷酸酶(NT5E)和A1腺苷受体(A1Rs)组成，提供 门禁。如果声刺激与脑电活动的干扰相结合，成年后幼年的可塑性可以重建。 听觉丘脑中的NT5E或A1R信号。这种可塑性发生在皮质MAP和个体ACX中 它是清醒的成年小鼠的神经元，并与音调辨别能力的长期改善有关。在……里面 在这种竞争性更新中，我们建议检验我们的假设，即丘脑中的腺苷机械是 在ACX MAP期间，将信息从调制投射传递到丘脑的主调节器 成人的可塑性。在目标1中，我们将通过将声音与激活的 在激活或停用门控机构的同时调节投射。在目标2中，我们将探索 通过研究腺苷的年龄依赖性终止早期临界期的分子机制 制作。在目标3中，我们将确定浇注机制的时间尺度。使用快速扫描循环 在清醒小鼠的伏安法中，我们发现腺苷在听觉丘脑和 大脑皮质对声音的反应。我们建议阐明这种声音诱发的机制和动力学。 腺苷在早期关键期前后的释放及其对丘脑放电的影响 声音刺激时的中继神经元和皮质神经元。从这些研究中获得的知识将提供 为进一步阐明听觉记忆的细胞和分子机制奠定了基础。

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.