INCREASE OF INPUT SYNCHRONY FACILITATION BY NEUROMODULATION AND HOMEOSTATIC PLASTICITY OF SODIUM CHANNELS

Neuronal coding describes how neurons represent information. Beyond firing rate coding, the brain also uses timing: precise action potential timing influence information transmission between neurons. Zbili et al. (2020) showed that single axons detect input synchrony. Asynchronous inputs depolarize neurons before spiking and partially inactivate Nav channels, whereas synchronous inputs trigger spikes straight from the resting membrane potential, preserving Nav availability and enhancing neurotransmitter release. This timing-dependent mechanism is called input synchrony facilitation (ISF).
We investigated the effect of lowering axonal Nav channel availability on ISF, either through neuromodulation or homeostatic plasticity of sodium channels. Using dual patch-clamp recordings from monosynaptically connected pairs of CA3 pyramidal neurons in organotypic hippocampal slices from Wistar rats, we assessed changes in transmission. We also examined which Nav channel subtypes contribute to this modulation.
D1 receptors were activated with SKF 81297 (20 µM). Although sodium currents decreased, ISF was unchanged. Muscarinic receptors were activated with carbachol (0.5 µM), which reduced sodium currents and significantly increased ISF.
Blocking Nav1.2 with hwtx (300 nM) reduced EPSC amplitude, increased their latency, and increased ISF, indicating Nav1.2 contribute to axonal conduction and glutamate release.
In PTX treated slices, EPSC were smaller and their latency increased. Presynaptic action potentials showed reduced peak and maximal depolarisation speed, consistent with homeostatic downregulation of Nav channels. ISF was also significantly enhanced.
We conclude that neuromodulation or homeostatic plasticity of sodium channels affect ISF in the hippocampus.