Cortical Circuits Underlying Higher Cognitive Functions including Working Memory and Language

Higher cognitive tasks are achieved through the concerted operation of multiple areas of the cerebral cortex and subcortical structures. Especially important in the "neurobiology of thought" is the operation of the prefrontal cortices. One of our goals is to understand the functional architecture of the prefrontal cortex and the role it plays in both normal and abnormal cognitive function. One topic of particular interest is working memory—that form of memory that temporarily stores useful information during the performance of a sequence of tasks.

Fundamentals of Local Cortical Circuit Operation and Modulation

The 2-3 mm thick sheet that comprises the cerebral cortex consists of a repeating array of stereotypical neuronal elements interconnected vertically and horizontally. The operation of the cerebral cortex can be thought of as the interaction of large numbers of local cortical microcircuits. Understanding the precise mechanisms by which these local cortical circuits operate, and how they are modulated or changed in health and disease, is essential to understanding the operation of the cerebral cortex as a whole.

Cellular Biology of Cortical Neurons and the Mechanisms by Which They Communicate

The main constituent of the cerebral cortex is the cortical pyramidal cell. Along with non-pyramidal cells, these neurons form the powerhouses of the cerebral cortex. Operation and interaction of the billions of cortical neurons and their synapses is what allows the cortex to perform its task: the generation of human cognition and thought. We seek to understand how the fundamental building blocks of the cerebral cortex operate, including: pyramidal cells, non-pyramidal cells, and their synaptic interconnections.

Development and Evolution of the Cerebral Cortex

One of the most fundamental questions in biology is how cortical circuitry, which subserves the highest cognitive functions, develops in each individual during brain evolution. Although the differences among mammalian genomes are relatively small, they produce changes not only in the number of neurons but also in the areal, laminar, cellular, circuit and synaptic level that significantly affect the brain's cognitive capacity. A remarkable aspect of cortical development is that none of its constituent neurons, even in the large primate cerebrum, are generated within the cortex itself, but rather migrate from the place of their origin to their proper laminar and areal positions (see animation). We use the most advanced approaches, ranging from molecular genetic and cell biology, to explore developmental mechanisms that enable formation of the cerebral cortex.

Genetic Drivers of Cortical Development

Molecular and cellular mechanisms that generate human-specific distinctions in the organization and function of the cerebral cortex, using recent advances in understanding the role of non-coding DNA and RNA, in development and evolution of primate cerebral cortex, culminating in humans.