TY - JOUR
T1 - Glycinergic Transmission Shaped by the Corelease of GABA in a Mammalian Auditory Synapse
AU - Lu, Tao
AU - Rubio, Maria E.
AU - Trussell, Laurence O.
N1 - Funding Information:
We thank Drs. Gail Mandel, Trillium Blackmer, and Hai Huang for critical comments; and Dr. Viktor Derkach for assistance with transfections. Supported by NIH grants DC04455 to L.O.T and DC006881-01A2 to M.E.R. NSF DBI-0420580 contributed funds to purchase the Tecnai 12 Biotwin.
PY - 2008/2/28
Y1 - 2008/2/28
N2 - The firing pattern of neurons is shaped by the convergence of excitation and inhibition, each with finely tuned magnitude and duration. In an auditory brainstem nucleus, glycinergic inhibition features fast decay kinetics, the mechanism of which is unknown. By applying glycine to native or recombinant glycine receptors, we show that response decay times are accelerated by addition of GABA, a weak partial agonist of glycine receptors. Systematic variation in agonist exposure time revealed that fast synaptic time course may be achieved with submillisecond exposures to mixtures of glycine and GABA at physiological concentrations. Accordingly, presynaptic terminals generally contained both transmitters, and depleting terminals of GABA slowed glycinergic synaptic currents. Thus, coreleased GABA accelerates glycinergic transmission by acting directly on glycine receptors, narrowing the time window for effective inhibition. Packaging both weak and strong agonists in vesicles may be a general means by which presynaptic neurons regulate the duration of postsynaptic responses.
AB - The firing pattern of neurons is shaped by the convergence of excitation and inhibition, each with finely tuned magnitude and duration. In an auditory brainstem nucleus, glycinergic inhibition features fast decay kinetics, the mechanism of which is unknown. By applying glycine to native or recombinant glycine receptors, we show that response decay times are accelerated by addition of GABA, a weak partial agonist of glycine receptors. Systematic variation in agonist exposure time revealed that fast synaptic time course may be achieved with submillisecond exposures to mixtures of glycine and GABA at physiological concentrations. Accordingly, presynaptic terminals generally contained both transmitters, and depleting terminals of GABA slowed glycinergic synaptic currents. Thus, coreleased GABA accelerates glycinergic transmission by acting directly on glycine receptors, narrowing the time window for effective inhibition. Packaging both weak and strong agonists in vesicles may be a general means by which presynaptic neurons regulate the duration of postsynaptic responses.
KW - MOLNEURO
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=39449128016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39449128016&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2007.12.010
DO - 10.1016/j.neuron.2007.12.010
M3 - Article
C2 - 18304482
AN - SCOPUS:39449128016
SN - 0896-6273
VL - 57
SP - 524
EP - 535
JO - Neuron
JF - Neuron
IS - 4
ER -