NMDA receptor-mediated Na+ signals in spines and dendrites

Spines and dendrites of central neurons represent an important site of synaptic signaling and integration. Here we identify a new, synaptically mediated spine signal with unique properties. Using two-photon Na+ imaging, we show that suprathreshold synaptic stimulation leads to transient increases in Na+ concentration in postsynaptic spines and their adjacent dendrites. This local signal is restricted to a dendritic domain near the site of synaptic input. In presumed active spines within this domain, the Na+ level increases by 30-40 mM even during short bursts of synaptic stimulation. During a long-term potentiation induction protocol (100 Hz, 1 sec), the Na+ level in the active spines reaches peak amplitudes of similar to 100 mM. We find that the Na+ transients are mainly mediated by Na+ entry through NMDA receptor channels and are detected during the coincident occurrence of synaptic potentials and backpropagating action potentials. The large amplitudes of the Na+ transients and their location on dendritic spines suggest that this signal is an important determinant of electrical and biochemical spine characteristics.