An old problem in the study of synaptic integration has been to establish whether dendrites have mechanisms to increase the strength of distal synapses, or if the influence of these connections on axon potential generation is actually small because they are attenuated while travelling towards the cell body. Although this problem was laid out more than 40 years ago by Rall's theoretical analysis, the experimental attention it has received has been surprisingly scarce. Now, in the September issue of Nature Neuroscience, Magee and Cook have revisited this question to discover that distal synapses do count as much as proximal ones because the farther they are from the soma, the stronger they get.

Magee and Cook measured synaptic currents simultaneously from the soma and from the apical dendrite of a single hippocampal pyramidal cell, and varied systematically the recording site on the dendrite. By evoking transmitter release close to the dendritic recording, they obtained compelling evidence that the cable properties of the dendrite filter the synaptic currents, reducing their amplitude. At the same time, however, synapses get stronger with increasing distance from the cell body and, as a consequence, the amplitude of the responses at the soma is homogeneous regardless of the site of synaptic input.

What are the cellular mechanisms that account for this amplitude normalization? We do not know yet, but there are several likely possibilities, such as an increase in the number of vesicles released at each synapse, or changes in the number or the properties of postsynaptic receptors. Regardless of the mechanism, the findings of Magee and Cook will challenge our conventional view of how dendrites work and may require us to rewrite some of our current neurophysiology textbooks.