Shaping dendritic NMDA spikes by timed synaptic inhibition: Implications for the I/O properties of cortical neurons

The pronounced, long lasting, regenerative NMDA-spike is initiated in individual dendritic branches of different types of neurons and is known to play a key role in dendritic computations and plasticity. Combining dynamic system theory and computational approaches, we systematically analyzed how timed synaptic inhibition activated during the NMDA-spike time-course, sculpts this spike and its associated current influx. When impinging on its early phase, individual GABAergic synapse activation transiently, but strongly, dampened the NMDA-spike; later inhibition prematurely terminated it. This inhibition reduced the NMDA-mediated Ca2+ current by up to 60%. NMDA-spikes in distal dendritic branches/spines are longer lasting and more resilient to inhibition, and thus enhance synaptic plasticity at these branches. Examination of this sensitivity of the NMDA-spike to well-timed synaptic inhibition suggests that NMDA-spikes are highly modifiable signals which enable sparse weak distal dendritic inhibition to finely tune both the neuron's output spikes as well as the branch's/spine's Ca2+ current associated with the local NMDA spike.