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 lifespan, 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 principle 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 M1 muscarinic receptors that downregulate adenosine inhibition of neurotransmitter release acting through A1 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 lifespan and, therefore, may be a cellular substrate of RF plasticity in both neonate and mature animals.

Modulation of synaptic function through the α-neurexin–specific ligand neurexophilin-1

“…In 20-Hz stimulus trains, consisting of 10 pulses, the ratios were defined as the 10th to the 1st, the 4th to the 1st, and the 2nd to the 1st amplitude. For pharmacological blocking, 200 μM picrotoxin or 50 μM gabazine was added to the pipette solution to block GABA A R intracellularly (79)(80)(81)(82)(83), and PPR was measured immediately or after 10 min, as indicated. Bicuculline (2 μM) and/or 20 μM CGP-55845 was added to the bathing solution to block GABA A R and GABA B R. Data acquisition and statistical analysis.…”

Auditory map plasticity: diversity in causes and consequences

“…The brief developmental window for AI tonotopic map plasticity may also be regulated by long-term potentiation and depression of thalamocortical synapses. Recent evidence shows that thalamocortical synaptic plasticity is lost but not gone after an early period of infant development [120]. Thalamocortical synaptic long-term potentiation can be rescued in acute slices from the adult auditory cortex when cortical disinhibition is paired with concomitant activation of cholingeric nucleus basalis axons, suggesting a separate type of cholinergic gating mechanism for map reorganization in developing and adult brains [121*].…”

Listening to another sense: somatosensory integration in the auditory system

“…Plasticity of the synapses mediating this communication were thought to be limited to the early stages of development but recent research indicates that the TC projections to the auditory cortex can exhibit long-term potentiation at various stages of development, but become “gated” with age (Chun, et al, 2013). For instance, cholinergic activation can release presynaptic gating through muscarinic receptors M(1) that down-regulate adenosine inhibition of neurotransmitter release (Blundon, et al, 2011). Once presynaptic gating is released, the TC synapse can express long term potentiation through metabotropic glutamate receptors postsynaptically (Blundon, et al, 2011).…”

“…For instance, cholinergic activation can release presynaptic gating through muscarinic receptors M(1) that down-regulate adenosine inhibition of neurotransmitter release (Blundon, et al, 2011). Once presynaptic gating is released, the TC synapse can express long term potentiation through metabotropic glutamate receptors postsynaptically (Blundon, et al, 2011). Interestingly, consecutive sound presentations can induce changes in the firing pattern of the thalamic neurons.…”