Activity-dependent long-term potentiation of electrical synapses in the mammalian thalamus

Abstract

Long-term potentiation results from spiking in one cell of an electrically coupled pair. Asymmetry of synapses increases following unidirectional activity. We suggest a calcium-based rule for electrical synapse plasticity. Abstract 2Activity-dependent changes of synapse strength have been extensively characterized at 3 chemical synapses, but the relationship between physiological forms of activity and strength at 4 electrical synapses remains poorly understood. For mammalian electrical synapses composed 5 of hexomers of connexin36, physiological forms of neuronal activity in coupled pairs has thus far 6 have only been linked to long-term depression; activity that results in strengthening of electrical 7 synapses has not yet been identified. The thalamic reticular nucleus (TRN), a central brain area 8 primarily connected by gap junctional (electrical) synapses, regulates cortical attention to the 9 sensory surround. Bidirectional plasticity of electrical synapses may be a key mechanism 10 underlying these processes in both healthy and diseased states. Here we show in electrically 11 coupled TRN pairs that tonic spiking in one neuron results in long-term potentiation of electrical 12 synapses between coupled pairs of TRN neurons. Potentiation is expressed asymmetrically, 13indicating that regulation of connectivity depends on the direction of use. Further, potentiation 14 depends on calcium flux, and we thus propose a calcium-based activity rule for bidirectional 15 plasticity of electrical synapse strength. Because electrical synapses dominate intra-TRN 16 connectivity, these synapses and their modifications are key regulators of thalamic attention 17 circuitry. More broadly, bidirectional modifications of electrical synapses are likely to be a 18 widespread and powerful principle for ongoing, dynamic reorganization of neuronal circuitry 19 across the brain. 20