Activity-dependent Long-Term Potentiation of Electrical Synapses in the Mammalian Thalamus

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