Timed Synaptic Inhibition Shapes NMDA Spikes, Influencing Local Dendritic Processing and Global I/O Properties of Cortical Neurons

Abstract

The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computational approaches, we now explore how the timing of synaptic inhibition affects the NMDA spike and its associated membrane current. When impinging on its early phase, individual inhibitory synapses strongly, but transiently, dampen the NMDA spike; later inhibition prematurely terminates it. A single inhibitory synapse reduces the NMDA-mediated Ca2+ current, a key player in plasticity, by up to 45%. NMDA spikes in distal dendritic branches/spines are longer-lasting and more resilient to inhibition, enhancing synaptic plasticity at these branches. We conclude that NMDA spikes are highly sensitive to dendritic inhibition; sparse weak inhibition can finely tune synaptic plasticity both locally at the dendritic branch level and globally at the level of the neuron's output. The NMDA spike is a nonlinear dendritic phenomenon involved in synaptic plasticity and in shaping the I/O properties of neurons. Doron et al. use a theoretical approach to study the fine-tuned and powerful modulation of the NMDA spike by timed synaptic inhibition. They provide a mechanistic explanation for the interaction between timed inhibition and excitation and explore the implications for dendritic and somatic computations.