From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors.

From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Research Abstract Details 

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From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Abstract Text:

Peer Wulff,Thomas Goetz,Elli ,Anni-Maija Linden,Massimiliano Renzi,Jerome D Swinny,Olga Y Vekovischeva,Werner Sieghart,Peter Somogyi,Esa R Korpi,Mark Farrant,William Wisden,

In mammals, identifying the contribution of specific neurons or networks to behavior is a key challenge. Here we describe an approach that facilitates this process by enabling the rapid modulation of synaptic inhibition in defined cell populations. Binding of zolpidem, a systemically active allosteric modulator that enhances the function of the GABAA receptor, requires a phenylalanine residue (Phe77) in the gamma2 subunit. Mice in which this residue is changed to isoleucine are insensitive to zolpidem. By Cre recombinase-induced swapping of the gamma2 subunit (that is, exchanging Ile77 for Phe77), zolpidem sensitivity can be restored to GABAA receptors in chosen cell types. We demonstrate the power of this method in the cerebellum, where zolpidem rapidly induces significant motor deficits when Purkinje cells are made uniquely sensitive to its action. This combined molecular and pharmacological technique has demonstrable advantages over targeted cell ablation and will be invaluable for investigating many neuronal circuits.

From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Publishing Authors By Initials

P Wulff,T Goetz,E ,AM Linden,M Renzi,JD Swinny,OY Vekovischeva,W Sieghart,P Somogyi,ER Korpi,M Farrant,W Wisden,

For similar nervous system: synapses research abstracts see: nervous system: synapses research

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From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature neuroscience

VOLUME: 10

Page Numbers: 923-9

Journal Abbreviation: Nat. Neurosci.

ISSN: 1097-6256

DAY: 17

MONTH: 06

YEAR: 2007

From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Information

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LANGUAGE: eng

NlmUniqueID: 9809671

From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Keywords Mesh Terms:

KEYWORDS: Synapses

MESH TERMS: physiology

Chemical & Substance for Abstract: From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Information

Substance Name: zolpidem

Registry Number: 82626-48-0

Grant and Affiliation Information for From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors.

AFFILIATION: Department of Clinical Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. p.wulff@abdn.ac.uk

Country: United States

AGENCY: United Kingdom Wellcome T

GRANT: G0601498(79979)

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MEDLINETA: Nat Neurosci

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