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- Title
Subsecond Regulation of Synaptically Released Dopamine by COMT in the Olfactory Bulb.
- Authors
Cockerham, Renee; Shaolin Liu; Cachope, Roger; Kiyokage, Emi; Cheer, Joseph F.; Shipley, Michael T.; Puche, Adam C.
- Abstract
The efficacy of neurotransmission depends on multiple factors, including presynaptic vesicular release of transmitter, postsynaptic receptor populations and clearance/inactivation of the transmitter. In the olfactory bulb (OB), short axon cells (SACs) form an interglomerular circuit that uses GABA and dopamine (DA) as cotransmitters. Selective optical activation of SACs causes GABA and DA corelease, resulting in a fast, postsynaptic GABA inhibitory response and a slower G-protein-coupled DA rebound excitation. In most systems, vesicular release of DA is cleared by the dopamine transporter (DAT). However, in the OB, high levels of specific DA metabolites suggest that enzymatic catalysis by catechol-O-methyl-transferase (COMT) predominates over DAT re-uptake. To assess this possibility we measured the amount of the DA breakdown enzyme, COMT, present in the OB. Compared with the striatum, the brain structure richest in DA terminals, the OB contains 50% more COMT per unit of tissue. Furthermore, the OB has dramatically less DAT compared with striatum, supporting the idea that COMT enzymatic breakdown, rather than DAT recycling, is the predominant mechanism for DA clearance. To functionally assess COMT inactivation of vesicular release of DA we used fast-scan cyclic voltammetry and pharmacological blockade of COMT. In mice expressing ChR2 in tyrosine hydroxylase-containing neurons, optical activation of SACs evoked robust DA release in the glomerular layer. The COMT inhibitor, tolcapone, increased the DA signal ~2-fold, whereas the DAT inhibitor GBR12909 had no effect. Together, these data indicate that the OB preferentially employs COMT enzymatic inactivation of vesicular release of DA.
- Subjects
REGULATION of neural transmission; CATECHOL-O-methyltransferase; BRAIN physiology; OLFACTORY bulb; DOPAMINE; G protein coupled receptors
- Publication
Journal of Neuroscience, 2016, Vol 36, Issue 29, p7779
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0658-16.2016