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Imaging the spread of reversible brain inactivations using fluorescent muscimol. 2008

Timothy A Allen, and Nandakumar S Narayanan, and Dianna B Kholodar-Smith, and Yanjun Zhao, and Mark Laubach, and Thomas H Brown
Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, United States.

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 0.5-1mm 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.

UI MeSH Term Description Entries
D008297 Male Males
D009118 Muscimol A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies. Agarin,Pantherine
D009433 Neural Inhibition The function of opposing or restraining the excitation of neurons or their target excitable cells. Inhibition, Neural
D011930 Reaction Time The time from the onset of a stimulus until a response is observed. Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D001931 Brain Mapping Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures. Brain Electrical Activity Mapping,Functional Cerebral Localization,Topographic Brain Mapping,Brain Mapping, Topographic,Functional Cerebral Localizations,Mapping, Brain,Mapping, Topographic Brain
D003213 Conditioning, Psychological Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response. Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
D003952 Diagnostic Imaging Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. Imaging, Diagnostic,Imaging, Medical,Medical Imaging
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D005456 Fluorescent Dyes Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. Flourescent Agent,Fluorescent Dye,Fluorescent Probe,Fluorescent Probes,Fluorochrome,Fluorochromes,Fluorogenic Substrates,Fluorescence Agents,Fluorescent Agents,Fluorogenic Substrate,Agents, Fluorescence,Agents, Fluorescent,Dyes, Fluorescent,Probes, Fluorescent,Substrates, Fluorogenic

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