The mammalian cerebral cortex is an immensely complex brain region that underlies the way in which we sense, act, and think. It is estimated that there are over 40 billion neurons and almost one hundred distinct neuronal cell types distributed over different areas and layers of the human cerebral cortex. The diversity of cortical neuronal cell types and the complexity of synaptic connections made by cortical neurons are critical factors in determining the cognitive capabilities of the mammalian brain. Cortical neurons can be broadly classified into two major groups: (i) pyramidal projection neurons and (ii) local circuit interneurons. The pyramidal projection neurons, representing the majority of cortical neurons, extend long axonal synaptic projections both within and beyond the cortex. By constituting the sole output and the largest input system of the cerebral cortex, as well as representing the major target of synaptic connections from other parts of the brain, pyramidal neurons occupy a central position in all cortical circuits. Local circuit neurons, also known as interneurons, account for 15-20% of cortical neurons. They function by modulating the activities or near-by neurons and do not extend projections beyond the cortex.

The cerebral cortex is structurally and functionally organized into columns, layers, and areas. Neurons at specific locations subserve functions characteristic of that location. Pyramidal neurons display remarkable laminar-specific differences in their morphologies, connectivities, and molecular identities. This structural organization of cortical pyramidal neurons gives rise to a functional "division of labor" within the cortex. For example, neurons residing in the upper layers (II-IV) make connections solely with other cortical neurons, either within the same hemisphere or the opposite hemisphere. In contrast, a majority of deep layer (V and VI) pyramidal neurons project to subcortical regions of the brain, and thus constitute the collective output system of the cortex.

The proper molecular identity and "wiring" of pyramidal cells are crucial to the development and function of the brain, and hence, to the behavior and survival of the organism as a whole. However, the molecular bases for laminar differences in pyramidal neuron identity, connectivity, and function remain largely unknown. Thus, our research is aimed at identifying the genetic and molecular mechanisms that differentiate pyramidal neurons from each other as well as from other cells in the cortex, and learning how these distinctions allow for separate areas and layers of the cerebral cortex to develop, evolve, and serve separate functions.