One assumption of cortical circuitry is that the strength of interactions between neurons and layers should be directly correlated to the amount of overlap between axons and dendrites of pyramidal cells. However, this assumption is cracking under evidence that the cell’s class (as determined by morphology, postsynaptic target, and protein complement) also helps to determine the strength of the synaptic connection between any two neurons. For example, Petreanu et al mapped the dendrite locations of channelrhodopsin-2 expressing pyramidal neurons in the neocortex to determine the axon-dendrite overlap between its various inputs. But when the researchers quantified the strength of inputs in a given column with identical laser powers, one layer of barrel cortex (L5B cells) had 62-fold less input from the posterior medial nucleus than another group (L5A cells), despite the fact that L5B dendrites had more overlap with posterior medial nucleus axons than L5A dendrites. So, the functional connectivity between neurons cannot simply be deduced from the structure and overlap of the axons and dendrites. The actual class and region of the two given neurons has predictive power for synaptic strength as well.
Brown SP, Hestrin S. 2009 Cell-type identity: a key to unlocking the function of neocortical circuits. Current Opinion in Neurobiology 19:415-421. doi:10.1016/j.conb.2009.07.011
Petreanu L, et al. 2009 The subcellular organization of neocortical excitatory connections. Nature 457:1142-1145. doi:10.1038/nature07709.