Research projects

How are the mammalian cortical networks built?

How are the mammalian cortical networks built?

The function of neural networks in the cerebral cortex of vertebrates relies on the interaction between two main classes of neurons, excitatory projection neurons and inhibitory interneurons. In these circuits, the output of excitatory neurons is fine-tuned and synchronised by the function of inhibitory neurons. Most notably, different classes of interneurons target different compartments of the pyramidal cells, the apical dendrites, the cell body, or even the axonal initial segment (AIS). Since the location of synaptic contacts largely determines their influence on the postsynaptic cell, it has been suggested that this elaborate organisation of inputs greatly increases the overall computational power of single neurons. One of the goals in my lab is to identify molecules involved in the formation of subcellular domain-restricted GABAergic synapses. To this end, we have carried out several unbiased genomic screens during comparing unique populations of interneurons that make synapses into different subcellular compartments. We have unveiled cell-specific molecular programs in cortical interneurons that emerge during the early wiring of these cells and underlie the specification of their connection patterns.

In addition to the molecular codes controlling the subcellular targeting of inhibitory synapses, interneurons precisely target different pyramidal cell subnetworks. We are currently investigating the cellular and molecular mechanisms underlying the assembly of these inhibitory circuitries. Unravelling the mechanisms that control the precise spatial organization of synapse formation during development should have a broad impact, from understanding plasticity in the healthy brain to identifying wiring abnormalities in disease.

ERC Wellcome Trust
How do cortical circuits response to enhanced sensory experience?

How do cortical circuits response to enhanced sensory experience?

What is different in a brain of 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 our childhood, it would stay 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.

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

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

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

Increasing evidence suggest that impaired development of specific neuronal circuits in the cerebral cortex is at the basis of several neuropsychiatric conditions, including autism and schizophrenia. Our research is focused in understanding the link of interneuron dysfunction and neurodevelopmental disorders.

MRC AIMS2 Trials Simon Foundation for the Autism Research Initiative

Research tools

Our Synapdomain tool allows a researcher to plot the expression of genes of interest in different cell types at the developmental stages when cortical circuits are assembled. RNA-seq data is available from Somatostatin cells (SST P5 and P10), Parvalbumin basket cells (PVBC P5 and P10) and Chandelier cells (ChC P8 and P10) as well as in interneurons (IN) at P0, pyramidal cells (PYR) at P12 and Oligodendrocytes (OLIG) at P10.


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