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Sensory sequence representation and discrimination in cortical circuits

皮层回路中的感觉序列表示和辨别

基本信息

批准号：
MR/P006639/1
负责人：
Miguel Maravall
金额：
$ 62.17万
依托单位：
University of Sussex
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FP006639%2F1
关键词：
Sensory sequence representation discrimination cortical

项目摘要

We experience the world in both space and time. To make sense of an environment, we need to be able to distinguish sequences, i.e., stimuli that are temporally patterned. Auditory and tactile stimuli can only be understood in terms of their temporal structure - a cue that the brain is particularly good at deciphering and remembering, for example when we learn a new song or a certain rhythm. The ability to generate and decode sequences of electrical activity is ubiquitous throughout the brain. Moreover, sequence learning and the processing of temporal duration are impaired in psychiatric disorders including depression and schizophrenia. Yet despite this centrality of sequence selectivity, remarkably little is known about its substrates in the brain. The chain of events from when a sequential temporal pattern is first reflected in the electrical activity of neurons to when it is classified as an "object," a meaningful entity, remains unknown. This is a major gap in our functional understanding of the brain. The goal of this project is to understand how representations of sequences emerge from the activity of populations of neurons in the cerebral cortex - the part of the brain that combines information from the senses, assigns it a meaning, relates it to earlier experience and decides on a response. To show how electrical activity in neurons relates to sequence recognition, it is necessary to link neuronal responses during presentation of a sequence to a specific behaviour showing that the subject distinguishes the sequence. To this end, we have created a novel behavioural task that is successfully performed by mice as well as by humans. Mice learn to detect arbitrary sequences of stimulation delivered to their whisker - tactile "songs" or "words." The sequences presented differ only in their temporal patterning, and mice learn to recognise a particular sequence for a reward. This experimental design is designed to allow us to search for general principles of sequence recognition in the brain, and specifically to test whether neurons sensitive to a given sequence reside in sensory areas of the cortex. We propose to combine this design with powerful new techniques for examining and manipulating brain activity. We will use methods of electrophysiology and two-photon imaging, already established in our laboratory, to record activity. Recordings will be targeted to groups of neurons in the cerebral cortex by means of state-of-the-art genetic and imaging tools. These experiments will allow us to uncover the neuronal activity related to the controlled sensory behaviour and identify neurons that are selective to a particular sequence. Our research will provide new insights into how neuronal circuits process information over time to give rise to sensation and perception. Because the neuronal circuitry in sensory areas of the cerebral cortex is similar in different mammalian species, this new knowledge will be relevant across species and will apply to human sequence learning as well. The outcome will have implications beyond improving our fundamental understanding of information flow through cortical neurons. As sequence processing is often impaired in disorders that perturb the normal establishment of neuronal circuits in the cortex, our approach will help the understanding of the functional effects of those disorders, and provide an assay for testing neurobiological models of brain pathologies.

我们在空间和时间中体验世界。为了理解环境，我们需要能够区分序列，即，时间模式化的刺激。听觉和触觉刺激只能根据它们的时间结构来理解-这表明大脑特别擅长破译和记忆，例如当我们学习一首新歌或某种节奏时。产生和解码电活动序列的能力在整个大脑中无处不在。此外，在包括抑郁症和精神分裂症在内的精神疾病中，序列学习和时间长度的处理受损。然而，尽管序列选择性具有这种中心性，但人们对其在大脑中的底物知之甚少。从一个连续的时间模式第一次反映在神经元的电活动中，到它被归类为一个“对象”，一个有意义的实体，这一系列的事件仍然是未知的。这是我们对大脑功能理解的一个主要空白。这个项目的目标是了解序列的表征是如何从大脑皮层神经元群体的活动中出现的-大脑皮层是大脑的一部分，它结合来自感官的信息，赋予它一个意义，将其与早期经验联系起来，并决定反应。为了显示神经元的电活动如何与序列识别相关，有必要将序列呈现期间的神经元反应与显示受试者区分序列的特定行为联系起来。为此，我们创造了一种新的行为任务，小鼠和人类都成功地完成了这项任务。老鼠学会检测传递到它们胡须上的任意序列的刺激--触觉“歌曲”或“单词”。“呈现的序列仅在时间模式上有所不同，小鼠学会识别特定的序列以获得奖励。这个实验设计的目的是为了让我们寻找大脑中序列识别的一般原理，特别是为了测试对给定序列敏感的神经元是否存在于皮层的感觉区域。我们建议将联合收割机与强大的新技术结合起来，以检查和操纵大脑活动。我们将使用我们实验室已经建立的电生理学和双光子成像方法来记录活动。记录将通过最先进的遗传和成像工具针对大脑皮层中的神经元组。这些实验将使我们能够揭示与受控感觉行为相关的神经元活动，并识别对特定序列具有选择性的神经元。我们的研究将为神经元回路如何随着时间的推移处理信息以产生感觉和感知提供新的见解。由于大脑皮层感觉区域的神经元回路在不同的哺乳动物物种中是相似的，这一新知识将与不同物种相关，也将适用于人类的序列学习。该结果的影响将超出改善我们对通过皮质神经元的信息流的基本理解。由于序列处理往往是受损的紊乱，扰乱了正常建立的神经元回路在皮层，我们的方法将有助于了解这些疾病的功能影响，并提供一个测试大脑病理的神经生物学模型的测定。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sequence Learning Induces Selectivity to Multiple Task Parameters in Mouse Somatosensory Cortex.

DOI：
10.1016/j.cub.2020.10.059
发表时间：
2021-02-08
期刊：
Current biology : CB
影响因子：
0
作者：
Bale MR;Bitzidou M;Giusto E;Kinghorn P;Maravall M
通讯作者：
Maravall M

Learning and recognition of tactile temporal sequences by mice and humans

DOI：
10.7554/elife.27333
发表时间：
2017-08-16
期刊：
ELIFE
影响因子：
7.7
作者：
Bale, Michael R.;Bitzidou, Malamati;Maravall, Miguel
通讯作者：
Maravall, Miguel

Non-telecentric two-photon microscopy for 3D random access mesoscale imaging.

DOI：
10.1038/s41467-022-28192-0
发表时间：
2022-01-27
期刊：
Nature communications
影响因子：
16.6
作者：
Janiak FK;Bartel P;Bale MR;Yoshimatsu T;Komulainen E;Zhou M;Staras K;Prieto-Godino LL;Euler T;Maravall M;Baden T
通讯作者：
Baden T

Organization of sensory feature selectivity in the whisker system.