In the cerebral cortex, local circuits consist of tens of thousands of neurons, each of which makes thousands of synaptic connections. Perhaps the biggest impediment to understanding these networks is that we have no wiring diagrams of their interconnections. Even if we had a partial or complete wiring diagram, however, understanding the network would also require information about each neuron's function. Here we show that the relationship between structure and function can be studied in the cortex with a combination of in vivo physiology and network anatomy. We used two-photon calcium imaging to characterize a functional property—the preferred stimulus orientation—of a group of neurons in the mouse primary visual cortex. We then used large-scale electron microscopy (EM) of serial thin sections to trace a portion of these neurons’ local network. Consistent with a prediction from recent physiological experiments, inhibitory interneurons received convergent anatomical input from nearby excitatory neurons with a broad range of preferred orientations, although weak biases could not be rejected.

Extensive simulations of PAMAM dendrimer generation 2 were performed at several pH conditions with explicit water molecules, to obtain proper conditions and validity for additional simulations without explicit water. Within the range of validity, simulation without water greatly extends the size and duration of practical simulations. We investigated the effects of long-range interaction parameters such as interaction distance and dielectric constant for molecular dynamics simulations of PAMAM dendrimer without water, concluding that charged dendrimer simulation with distance-dependent dielectric constant but without cutoff distance best mimics explicit water results. Structural variations of PAMAM dendrimers were analyzed as a function of pH and dendrimer generation using MD simulations with these long-range interaction parameters. Globular and loosely compact structures at high pH (g10) show conservation of atom density distribution across dendrimer generations. Highly ordered extended structures at low pH (e4) present an increasingly hollow interior as dendrimer generation grows, resulting in more open structure which provides easier access by chemical agents. By contrast, significant branch back-folding occurred at neutral pH in addition to major peripheral distribution of the terminal groups, yielding higher interior density in the intermediate radial region between the center and the maximum radius as the generation grows. Higher generation dendrimers provide a cavity surrounded by dense atom populations, producing a more stable agent carrier. Transition to high-density packing occurs between generations 4 and 5. Volume differences between neutral and low pH calculated from R G show a dramatic increase beginning at generation 5.