Imaging the spread of reversible brain inactivations using fluorescent muscimol

Timothy A Allen; Nandakumar S Narayanan; Dianna B Kholodar-Smith; Yanjun Zhao; Mark Laubach; Thomas H Brown

doi:10.1016/j.jneumeth.2008.01.033

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Imaging the spread of reversible brain inactivations using fluorescent muscimol

Journal article

Peer reviewed

Imaging the spread of reversible brain inactivations using fluorescent muscimol

Timothy A Allen, Nandakumar S Narayanan, Dianna B Kholodar-Smith, Yanjun Zhao, Mark Laubach and Thomas H Brown

Journal of neuroscience methods, Vol.171(1), pp.30-38

2008

DOI: 10.1016/j.jneumeth.2008.01.033

PMCID: PMC2440580

PMID: 18377997

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https://figshare.com/articles/preprint/Imaging_the_spread_of_reversible_brain_inactivations_using_fluorescent_muscimol/23888880View

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Abstract

Muscimol is a GABA A-agonist that causes rapid and reversible suppression of neurophysiological activity. Interpretations of the effects of muscimol infusions into the brain have been limited because of uncertainty about spread of the drug around the injection site. To solve this problem, the present study explored the use of a fluorophore-conjugated muscimol molecule (FCM). Whole-cell recordings from horizontal brain slices demonstrated that bath-applied FCM acts like muscimol in reversibly suppressing excitatory synaptic transmission. Two types of in vivo experiments demonstrated that the behavioral effects of FCM infusion are similar to the behavioral effects of muscimol infusion. FCM infusion into the rat amygdala before fear conditioning impaired both cued and contextual freezing, which were tested 24 or 48 h later. Normal fear conditioning occurred when these same rats were subsequently given phosphate-buffered saline infusions. FCM infusion into the dorsomedial prefrontal cortex impaired accuracy during a delayed-response task. Histological analysis showed that the region of fluorescence was restricted to 0.5–1 mm from the injection site. Myelinated fiber tracts acted as diffusional barriers, thereby shaping the overall spread of fluorescence. The results suggest that FCM is indeed useful for exploring the function of small brain regions.

GABA A-agonist

Prefrontal cortex

Amygdala

Lesions

Fear conditioning

Details

Title: Subtitle: Imaging the spread of reversible brain inactivations using fluorescent muscimol
Creators: Timothy A Allen - Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States
Nandakumar S Narayanan - Interneuroscience Program, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States
Dianna B Kholodar-Smith - Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States
Yanjun Zhao - Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States
Mark Laubach - Department of Neurobiology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States
Thomas H Brown - Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States
Resource Type: Journal article
Publication Details: Journal of neuroscience methods, Vol.171(1), pp.30-38
DOI: 10.1016/j.jneumeth.2008.01.033
PMID: 18377997
PMCID: PMC2440580
NLM abbreviation: J Neurosci Methods
ISSN: 0165-0270
eISSN: 1872-678X
Publisher: Elsevier B.V
Language: English
Date published: 2008
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020775702771

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