Metaplasticity of cortical glutamatergic LTP by diurnal intracellular chloride dynamics

Neural plasticity varies depending on the time of day and preceding sleep-wake history. It is unclear however, how diurnal changes in cellular physiology modulate a neuron's propensity to exhibit synaptic plasticity. Recently it has been shown that cortical pyramidal neurons exhibit diurnal changes in their transmembrane chloride gradients, which shift the equilibrium potential for GABAA receptors (EGABAA). Here we demonstrate that diurnal EGABAA affects membrane potential dynamics and glutamatergic long-term potentiation (LTP) elicited by high-frequency spiking activity in pyramidal neurons of mouse cortex. More depolarized EGABAA values associated with the active period facilitate LTP induction by promoting residual depolarization during synaptically-evoked spiking. Diurnal differences in LTP can be reversed by switching the EGABAA-dependent effects on membrane potential dynamics, either by direct current injection or pharmacologically altering EGABAA. These findings identify EGABAA as a metaplastic regulator of glutamatergic synaptic potentiation, which has implications for understanding synaptic plasticity during waking and sleep. ### Competing Interest Statement The authors have declared no competing interest.