Lattice system of functionally distinct cell types in the neocortex.

The mammalian neocortex contains many cell types, but whether they organize into repeated structures has been unclear. We discovered that major cell types in neocortical layer 5 form a lattice structure in many brain areas. Large-scale three-dimensional imaging revealed that distinct types of excitatory and inhibitory neurons form cell type-specific radial clusters termed microcolumns. Thousands of microcolumns, in turn, are patterned into a hexagonal mosaic tessellating diverse regions of the neocortex. Microcolumn neurons demonstrate synchronized in vivo activity and visual responses with similar orientation preference and ocular dominance. In early postnatal development, microcolumns are coupled by cell type-specific gap junctions and later serve as hubs for convergent synaptic inputs. Thus, layer 5 neurons organize into a brainwide modular system, providing a template for cortical processing.

Periodic organization of a major subtype of pyramidal neurons in neocortical layer V.

A major question in neocortical research is the extent to which neuronal organization is stereotyped. Previous studies have revealed functional clustering and neuronal interactions among cortical neurons located within tens of micrometers in the tangential orientation (orientation parallel to the pial surface). In the tangential orientation at this scale, however, it is unknown whether the distribution of neuronal subtypes is random or has any stereotypy. We found that the tangential arrangement of subcerebral projection neurons, which are a major pyramidal neuron subtype in mouse layer V, was not random but significantly periodic. This periodicity, which was observed in multiple cortical areas, had a typical wavelength of 30 µm. Under specific visual stimulation, neurons in single repeating units exhibited strongly correlated c-Fos expression. Therefore, subcerebral projection neurons have a periodic arrangement, and neuronal activity leading to c-Fos expression is similar among neurons in the same repeating units. These results suggest that the neocortex has a periodic functional micro-organization composed of a major neuronal subtype in layer V.

Src-family protein tyrosine kinase negatively regulates cerebellar long-term depression.

Protein phosphorylation is a major mechanism for the regulation of synaptic transmission. Previous studies have shown that several serine/threonine kinases are involved in the induction of long-term depression (LTD) at excitatory synapses on a Purkinje neuron (PN) in the cerebellum. Here, we show that Src-family protein tyrosine kinases (SFKs) are involved in the regulation of the LTD induction. Intracellular application of c-Src suppressed LTD. We also show that application of a SFK-selective inhibitor PP2 recovered LTD from the suppression caused by the inhibition of mGluR1 activity. These results indicate that SFKs negatively regulate the LTD induction at excitatory synapses on a cerebellar PN.