Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits

New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum...

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Main Authors: Lin, Chia-Wei, Sim, Shuyin, Ainsworth, Alice, Okada, Masayoshi, Kelsch, Wolfgang, Lois, Carlos
Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Format: Article
Language:en_US
Published: Elsevier 2015
Online Access:http://hdl.handle.net/1721.1/96051
https://orcid.org/0000-0002-3470-8125
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author Lin, Chia-Wei
Sim, Shuyin
Ainsworth, Alice
Okada, Masayoshi
Kelsch, Wolfgang
Lois, Carlos
author2 Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
author_facet Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Lin, Chia-Wei
Sim, Shuyin
Ainsworth, Alice
Okada, Masayoshi
Kelsch, Wolfgang
Lois, Carlos
author_sort Lin, Chia-Wei
collection MIT
description New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits.
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spelling mit-1721.1/960512022-09-26T13:27:55Z Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits Lin, Chia-Wei Sim, Shuyin Ainsworth, Alice Okada, Masayoshi Kelsch, Wolfgang Lois, Carlos Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Lin, Chia-Wei Sim, Shuyin Ainsworth, Alice Okada, Masayoshi Kelsch, Wolfgang Lois, Carlos New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits. 2015-03-17T18:14:38Z 2015-03-17T18:14:38Z 2010-01 2009-11 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/96051 Lin, Chia-Wei, Shuyin Sim, Alice Ainsworth, Masayoshi Okada, Wolfgang Kelsch, and Carlos Lois. “Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits.” Neuron 65, no. 1 (January 2010): 32–39. © 2010 Elsevier Inc. https://orcid.org/0000-0002-3470-8125 en_US http://dx.doi.org/10.1016/j.neuron.2009.12.001 Neuron Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier
spellingShingle Lin, Chia-Wei
Sim, Shuyin
Ainsworth, Alice
Okada, Masayoshi
Kelsch, Wolfgang
Lois, Carlos
Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
title Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
title_full Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
title_fullStr Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
title_full_unstemmed Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
title_short Genetically Increased Cell-Intrinsic Excitability Enhances Neuronal Integration into Adult Brain Circuits
title_sort genetically increased cell intrinsic excitability enhances neuronal integration into adult brain circuits
url http://hdl.handle.net/1721.1/96051
https://orcid.org/0000-0002-3470-8125
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