How are the mammalian cortical networks built?
All animal behaviours, from the simple movement of the worm to the sophisticated choreography of a ballet dancer, rely on exquisitely precise neuronal connectivity established during development. Understanding the rules orchestrating the assembly of neural circuits is undoubtedly one of the most significant challenges in neuroscience. One of the goals in my lab is to identify the principles governing the organisation of synaptic connections in the cerebral cortex. In the mammalian brain, neural circuits reach an extraordinary complexity in the cerebral cortex. Here, the excitatory principal cells' outputs are modulated and synchronised by the synapses they receive from many different classes of inhibitory interneurons. How are these myriads of synaptic connections organised? Using unbiased screens, we have discovered some molecular codes involved in the precise subcellular targeting of interneurons. In addition to their remarkable subcellular precision, inhibitory neurons are picky about the type of pyramidal cell they target. We are currently investigating the cellular and molecular programmes driving the assembly of specific subnetworks of pyramidal cells and interneurons (Wellcome Trust).
While other species have impressive abilities adapted to their unique environments, human cognitive competency remains unparalleled in scope and sophistication. Humans can think abstractly, imagine, create complex systems, use different languages, and engage in self-awareness, foresight, planning, and decision-making. How do humans acquire these complex abilities? The human cerebral cortex provides the structural basis for this unique potential. Still, the rules governing the wiring of cortical neurons in the developing human cortex remain unknown. We are currently investigating the cellular and molecular mechanisms underlying the assembly of these inhibitory circuitries in humans (Wellcome Discovery).