Glutamate receptors form hot spots on apical dendrites of neocortical pyramidal neurons

Apical dendrites of layer V cortical pyramidal neurons are a major target f or glutamatergic synaptic inputs from cortical and subcortical brain region s. Because innervation from these regions is somewhat laminar along the den drites, knowing the distribution of glutamate receptors on the apical dendr ites is of prime importance for understanding the function of neural circui ts in the neocortex. To examine this issue, we used infrared-guided laser s timulation combined with whole cell recordings to quantify the spatial dist ribution of glutamate receptors along the apical dendrites of layer V pyram idal neurons. Focally applied (<10 <mu>m) flash photolysis of caged glutama te, on the soma and along the apical dendrite revealed a highly nonuniform distribution of glutamate responsivity. Up to four membrane areas (extent 2 2 mum) of enhanced glutamate responsivity (hot spots) were detected on the dendrites with the amplitude and integral of glutamate-evoked responses at hot spots being three times larger than responses evoked at neighboring sit es. We found no association of these physiological hot spots with dendritic branch points. It appeared that the larger responses evoked at hot spots r esulted from an increase in activation of both alpha -amino-3-hydroxy-5-met hyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate. (NMDA) recep tors and not a recruitment of voltage-activated sodium or calcium conductan ces. Stimulation of hot spots did, however, facilitate the triggering of bo th Na+ spikes and Ca2+ spikes, suggesting that hot spots may serve as dendr itic initiation zones for regenerative spikes.