1. Higher-Order Thalamocortical Inputs Gate Synaptic Long-Term Potentiation via Disinhibition.
- Author
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Williams, Leena E. and Holtmaat, Anthony
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WHISKERS , *LONG-term potentiation , *THALAMOCORTICAL system , *PYRAMIDAL neurons , *METHYL aspartate receptors , *VASOACTIVE intestinal peptide , *OPTOGENETICS - Abstract
Summary Sensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons (PNs), largely mediated by synaptic long-term potentiation (LTP). The circuit mechanisms underlying cortical LTP remain unclear. In the mouse somatosensory cortex, LTP can be elicited in layer 2/3 PNs by rhythmic whisker stimulation. We dissected the synaptic circuitry underlying this type of plasticity in thalamocortical slices. We found that projections from higher-order, posterior medial thalamic complex (POm) are key to eliciting N-methyl-D-aspartate receptor (NMDAR)-dependent LTP of intracortical synapses. Paired activation of cortical and higher-order thalamocortical inputs increased vasoactive intestinal peptide (VIP) and parvalbumin (PV) interneuron (IN) activity and decreased somatostatin (SST) IN activity, which together disinhibited the PNs. VIP IN-mediated disinhibition was critical for inducing LTP. This study reveals a circuit motif in which higher-order thalamic inputs gate synaptic plasticity via disinhibition. This motif may allow contextual feedback to shape synaptic circuits that process first-order sensory information. Graphical Abstract Highlights • Activation of higher-order (HO) thalamic inputs facilitates intracortical LTP • HO inputs increase VIP and PV interneuron (IN) activity and decrease SST IN activity • The activation of VIP INs disinhibits L2/3 pyramidal neurons (PNs) • The HO-to-VIP circuit gates the intracortically driven LTP on PNs Using ex vivo patch-clamp recordings, optogenetics, and chemogenetics, Williams and Holtmaat dissect the circuits underlying sensory-driven LTP in the cortex. This reveals a circuit motif in which higher-order thalamocortical input gates plasticity of intracortical synapses via VIP-mediated disinhibition. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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