Research projects

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).

How do cortical circuits response to enhanced sensory experience?

What is different in the brain of one that has been exposed to enhanced sensory stimulation, compared with one that has not? For example, why is it much easier to learn a motor skill or a language early in life? And why, if we become competent in a new skill during childhood, would we stay with it for our entire life? Interneurons have a remarkable capability to sense changes in sensory experience and therefore occupy a unique position to orchestrate circuit remodelling. In this project, we aim to understand the mechanisms through which enhanced sensory experience during development sculpts cortical circuitries to improve behavioural performance (Experientia-ERC Advance; Wellcome Early Career Award).

Is there any link between interneuron cortical dysfunction and neurodevelopmental disorders?

Neuropsychiatric disorders, such as autism, epilepsy, and schizophrenia, are the leading source of disease burden in the developed world, as they begin early in life and contribute to lifelong incapacity or reduced longevity. Consequently, brain disorders will present an even greater public health challenge in the coming decades. Understanding the complex neurobiology underlying these disorders is crucial for developing new treatments. In this context, creating new animal models that mimic some symptoms of these devastating diseases provides a major opportunity to broaden the search for novel targets to treat neurodevelopmental disorders.

Increasing evidence suggests that impaired development of specific neuronal circuits in the cerebral cortex is at the basis of several neuropsychiatric conditions, including autism, epilepsy, and schizophrenia. Our lab research focuses on understanding the link between interneuron dysfunction and neurodevelopmental disorders using animal and human models (Wellcome Trust, Mental Health Collaborative Award; Simons Foundation pilot; MRC).