Quantitative mapping of the local and extrinsic sources of GABA and Reelin to the layer Ia neuropil in the adult rat neocortex

Inputs to apical dendritic tufts have been considered to be crucial for associative learning, attention and similar ''feedback'' interactions and are located in neocortical layer Ia. Excitatory thalamic projections to apical tufts in layer Ia have been well characterized and their role in the cortical circuit has been emphasized. In addition, the neuropil and the extracellular matrix surrounding apical tufts are highly reactive to GABA and to the glycoprotein Reelin, respectively. Recently it has been shown that the GABA inhibition on apical dendrites can reduce the output of pyramidal cells in layer V, however, the origin of 89 % of the symmetric synapses in layer I still remains unknown. In the present study we have systematically analyzed the origin of the GABAergic neuropil in neocortical layer Ia in a qualitative and quantitative manner, and investigated the possible extrinsic origin of the rich extracellular Reelin content of the same layer. We show that the inhibitory inputs in a given spot in layer I come from cortical projections and arise mainly from Martinotti cells located directly under that same spot. Double bouquet and bipolar cells may also project to layer Ia although to a lesser extent and the external globus pallidus and zona incerta provide the remaining inhibitory inputs. Finally, our results suggest that Martinotti cells are also the main source of Reelin in layer Ia. The present data will help in the understanding of the cortical circuit and why it changes in pathological conditions.