Long-term depression of synaptic inhibition is expressed postsynaptically in the developing auditory system

Eric H. Chang, Vibhakar C. Kotak, Dan Sanes

Research output: Contribution to journalArticle

Abstract

Inhibitory transmission is critically involved in the functional maturation of neural circuits within the brain. However, the mechanisms involved in its plasticity and development remain poorly understood. At an inhibitory synapse of the developing auditory brain stem, we used whole cell recordings to determine the site of induction and expression of long-term depression (LTD), a robust activity-dependent phenomenon that decreases inhibitory synaptic gain and is postulated to underlie synapse elimination. Recordings were obtained from lateral superior olivary (LSO) neurons, and hyperpolarizing inhibitory potentials were evoked by stimulation of the medial nucleus of the trapezoid body (MNTB). Both postsynaptic glycine and GABA A receptors could independently display LTD when isolated pharmacologically. Focal application of GABA, but not glycine, on the postsynaptic LSO neuron was sufficient to induce depression of the amino acid-evoked response, or MNTB-evoked inhibitory postsynaptic potentials. This GABA-mediated depression, in the absence of MNTB stimulation, was blocked by a GABAB, receptor antagonist. To assess whether a change in neurotransmitter release is associated with the LTD, the polyvalent cation, ruthenium red, was used to increase the frequency of miniature inhibitory synaptic events. Consistent with a postsynaptic locus of expression, we found that the mean amplitude of miniature events decreased after LTD with no change in their frequency of occurrence. Furthermore, there was no change in the paired-pulse ratio or release kinetics of evoked inhibitory responses. Together, these results provide direct evidence that activity-dependent LTD of inhibition has a postsynaptic locus of induction and alteration, and that GABA but not glycine plays a pivotal role.

Original languageEnglish (US)
Pages (from-to)1479-1488
Number of pages10
JournalJournal of Neurophysiology
Volume90
Issue number3
DOIs
StatePublished - Sep 1 2003

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Long-Term Synaptic Depression
Glycine
gamma-Aminobutyric Acid
Synapses
Neurons
Ruthenium Red
Inhibitory Postsynaptic Potentials
Patch-Clamp Techniques
GABA-A Receptors
Evoked Potentials
Brain Stem
Neurotransmitter Agents
Cations
Amino Acids
Brain
Trapezoid Body

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Long-term depression of synaptic inhibition is expressed postsynaptically in the developing auditory system. / Chang, Eric H.; Kotak, Vibhakar C.; Sanes, Dan.

In: Journal of Neurophysiology, Vol. 90, No. 3, 01.09.2003, p. 1479-1488.

Research output: Contribution to journalArticle

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