Document Detail


Endogenous signaling through alpha7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus.
MedLine Citation:
PMID:  20592195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs) and receive direct cholinergic innervation. We show here that functional alpha7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and alpha7-knock-out (alpha7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In alpha7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in alpha7KO mice. Interestingly, local infection with retroviral constructs to knockdown alpha7-mRNA mimics the alpha7KO phenotype, demonstrating that the relevant alpha7-nAChR signaling is cell autonomous. The results indicate a profound role for alpha7-nAChRs in adult neurogenesis and predict that alpha7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well.
Authors:
Nolan R Campbell; Catarina C Fernandes; Andrew W Halff; Darwin K Berg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  30     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-01     Completed Date:  2010-07-22     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8734-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / cytology,  physiology*
Aging
Animals
Cell Survival / physiology
Dendrites / physiology
Dentate Gyrus / cytology,  physiology*
Female
Gene Knockdown Techniques
Hippocampus / cytology,  physiology
Male
Membrane Potentials / physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neural Pathways / cytology,  physiology
Neurogenesis / physiology*
Neurons / cytology,  physiology*
Receptors, Nicotinic / genetics,  metabolism*
alpha7 Nicotinic Acetylcholine Receptor
gamma-Aminobutyric Acid / metabolism
Grant Support
ID/Acronym/Agency:
N0S35469//PHS HHS; NS012601/NS/NINDS NIH HHS; R01 NS012601/NS/NINDS NIH HHS; R01 NS012601-33/NS/NINDS NIH HHS; R01 NS012601-34/NS/NINDS NIH HHS; R01 NS012601-34S1/NS/NINDS NIH HHS; R01 NS012601-35/NS/NINDS NIH HHS; R01 NS035469/NS/NINDS NIH HHS; R01 NS035469-13/NS/NINDS NIH HHS; R01 NS035469-14A1/NS/NINDS NIH HHS; R01 NS035469-15/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Chrna7 protein, mouse; 0/Receptors, Nicotinic; 0/alpha7 Nicotinic Acetylcholine Receptor; 56-12-2/gamma-Aminobutyric Acid
Comments/Corrections

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