title: Presynaptic gating of postsynaptically expressed plasticity at mature thalamocortical synapses.
abstract: Thalamocortical (TC) projections provide the major pathway for ascending sensory information to the mammalian neocortex. Arrays of these projections form synaptic inputs on thalamorecipient neurons, thus contributing to the formation of receptive fields (RFs) in sensory cortices. Experience-dependent plasticity of RFs persists throughout an organism's life span but in adults requires activation of cholinergic inputs to the cortex. In contrast, synaptic plasticity at TC projections is limited to the early postnatal period. This disconnect led to the widespread belief that TC synapses are the principal site of RF plasticity only in neonatal sensory cortices, but that they lose this plasticity upon maturation. Here, we tested an alternative hypothesis that mature TC projections do not lose synaptic plasticity but rather acquire gating mechanisms that prevent the induction of synaptic plasticity. Using whole-cell recordings and direct measures of postsynaptic and presynaptic activity (two-photon glutamate uncaging and two-photon imaging of the FM 1-43 assay, respectively) at individual synapses in acute mouse brain slices that contain the auditory thalamus and cortex, we determined that long-term depression (LTD) persists at mature TC synapses but is gated presynaptically. Cholinergic activation releases presynaptic gating through M(1) muscarinic receptors that downregulate adenosine inhibition of neurotransmitter release acting through A(1) adenosine receptors. Once presynaptic gating is released, mature TC synapses can express LTD postsynaptically through group I metabotropic glutamate receptors. These results indicate that synaptic plasticity at TC synapses is preserved throughout the life span and, therefore, may be a cellular substrate of RF plasticity in both neonate and mature animals.
authors: Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105-3678, USA. stanislav.zakharenko@stjude.org
authors: Jay A
authors: JA
authors: Blundon
authors: Ildar T
authors: IT
authors: Bayazitov
authors: Stanislav S
authors: SS
authors: Zakharenko
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000172:deficiency; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013788:Thalamus / Q000166:cytology*
chemical_list: C440256:4-methoxy-7-nitroindolinyl-glutamate; C073804:FM1 43; D005971:Glutamates; D007211:Indoles; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D043682:Receptor, Adenosine A1