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      Coordinated Plasticity between Barrel Cortical Glutamatergic and GABAergic Neurons during Associative Memory

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          Abstract

          Neural plasticity is associated with memory formation. The coordinated refinement and interaction between cortical glutamatergic and GABAergic neurons remain elusive in associative memory, which we examine in a mouse model of associative learning. In the mice that show odorant-induced whisker motion after pairing whisker and odor stimulations, the barrel cortical glutamatergic and GABAergic neurons are recruited to encode the newly learnt odor signal alongside the innate whisker signal. These glutamatergic neurons are functionally upregulated, and GABAergic neurons are refined in a homeostatic manner. The mutual innervations between these glutamatergic and GABAergic neurons are upregulated. The analyses by high throughput sequencing show that certain microRNAs related to regulating synapses and neurons are involved in this cross-modal reflex. Thus, the coactivation of the sensory cortices through epigenetic processes recruits their glutamatergic and GABAergic neurons to be the associative memory cells as well as drive their coordinated refinements toward the optimal state for the storage of the associated signals.

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          Most cited references71

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          Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

          Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
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            Optogenetic stimulation of a hippocampal engram activates fear memory recall

            A specific memory is thought to be encoded by a sparse population of neurons 1,2 . These neurons can be tagged during learning for subsequent identification 3 and manipulation 4,5,6 . Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, a critical question of sufficiency remains: can one elicit the behavioral output of a specific memory by directly activating a population of neurons that was active during learning? Here we show that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behavior. We labeled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) 7,8 and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear conditioned mice with cells labeled by EYFP instead of ChR2. Finally, activation of cells labeled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context-specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
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              Synaptic plasticity, memory and the hippocampus: a neural network approach to causality.

              Two facts about the hippocampus have been common currency among neuroscientists for several decades. First, lesions of the hippocampus in humans prevent the acquisition of new episodic memories; second, activity-dependent synaptic plasticity is a prominent feature of hippocampal synapses. Given this background, the hypothesis that hippocampus-dependent memory is mediated, at least in part, by hippocampal synaptic plasticity has seemed as cogent in theory as it has been difficult to prove in practice. Here we argue that the recent development of transgenic molecular devices will encourage a shift from mechanistic investigations of synaptic plasticity in single neurons towards an analysis of how networks of neurons encode and represent memory, and we suggest ways in which this might be achieved. In the process, the hypothesis that synaptic plasticity is necessary and sufficient for information storage in the brain may finally be validated.
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                Author and article information

                Journal
                Neural Plast
                Neural Plast
                NP
                Neural Plasticity
                Hindawi Publishing Corporation
                2090-5904
                1687-5443
                2016
                14 December 2016
                : 2016
                : 5648390
                Affiliations
                1Department of Pathophysiology, Bengbu Medical College, Anhui 233000, China
                2State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing 100101, China
                3School of Pharmacy, Qingdao University, 38 Dengzhou, Shandong 266021, China
                Author notes
                *Jin-Hui Wang: jhw@ 123456ibp.ac.cn

                Academic Editor: Zygmunt Galdzicki

                Author information
                http://orcid.org/0000-0001-6934-3309
                Article
                10.1155/2016/5648390
                5192352
                28070425
                9678163f-1728-4d7f-b484-a55968a1bc82
                Copyright © 2016 Fenxia Yan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 July 2016
                : 16 October 2016
                : 9 November 2016
                Funding
                Funded by: National Basic Research Program
                Award ID: 2013CB531304
                Award ID: 2016YFC1307101
                Funded by: National Natural Science Foundation of China
                Award ID: 81671071
                Award ID: 81471123
                Categories
                Research Article

                Neurosciences
                Neurosciences

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