title: Long-term depression of synaptic inhibition is expressed postsynaptically in the developing auditory system.
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 GABAA 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.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Chang
authors.forename: Vibhakar C
authors.initials: VC
authors.lastname: Kotak
authors.forename: Dan H
authors.initials: DH
authors.lastname: Sanes
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D005849:Gerbillinae; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid