The neocortex, especially the frontal cortex, is particularly interconnected with almost all other brain areas. Although early anatomical work revealed that cortical neurons are very diverse in their morphologies, a comprehensive understanding of neocortical structure has remained elusive. Cortical neurons are divided into excitatory glutamatergic pyramidal cells and inhibitory GABAergic cells. We first identified a subtype of GABAergic neuron called 'fast-spiking basket cells' based on their axonal morphology and selective expression of the calcium-binding protein 'parvalbumin'. Since then, we have identified many additional subtypes of cortical GABAergic cells by examination of their morphological, physiological, and chemical properties. We have followed this up by investigating their synaptic structures with pyramidal cells. Our findings have provided a framework for analysis of the structure and function of neocortical circuits under normal as well as pathological conditions. In addition to the GABAergic cells, we are now also investigating the organization and connectivity of cortical pyramidal cells projecting to diverse brain areas, and the relationship between the local and long-distance recurrent subnetworks. Once we establish the organization of pyramidal and GABAergic cells in the neocortex, we would like to identify the mechanisms that drive their selective synaptic connectivity. To do this, we are using anatomical, molecular, and developmental techniques for identification of neocortical neuron groups, and electrophysiology and electron microscopy for circuit and synaptic transmission analysis. Our hope is that this new knowledge will provide insights into the function of the neocortex, as well as identify changes in cellular and circuit function that contribute to neurological and psychiatric disease.
Basic subtypes and connections of GABA cells and layer 5 pyramidal cells in the frontal cortex. Molecules expressed in GABA cells: AAc, alpha-actinin-2; CCK, cholecystokinin; CR, calretinin; NPY neuropeptide Y; PV, parvalbumin; SOM, somatostatin; VVA, binding with Vicia villosa. Pyramidal cell groups: CCS, crossed-corticostriatal cell; COM, commissural cell; CPn, corticopontine cell; CTh, corticothalamic cell; CSp, corticospinal cell.