Irala Lab

About the Irala Lab

The development of functional neuronal circuits depends on the proper formation and function of neuron-neuron connections, known as synapses. The balance between excitatory and inhibitory synaptic contacts (E/I balance) is crucial for correct brain function, and disruption of this balance is a hallmark of numerous neurodevelopmental disorders. Astrocytes, star-shaped glial cells of the central nervous system, have emerged as key regulators of both excitatory and inhibitory synaptic contacts. In our lab, we investigate the cellular and molecular mechanisms of astrocyte-neuron communication during brain development in health and disease. Our research focuses on how astrocytes control synaptic diversity and synaptic balance, shaping brain connectivity during development.

The team

The Irala lab is a dynamic and collaborative group of cell and molecular neurobiologists working together to decipher how astrocytes shape brain connectivity in health and disease.

Meet the Team

Our research summary

Astrocytes are master regulators of synaptic diversity and balance. In the developing brain, the bulk of synaptogenesis occurs after astrocytes are born, and through cell adhesion molecules and secreted factors, they orchestrate a wide variety of synaptic contacts. Given the significant heterogeneity of inhibitory neurons and their synaptic contacts, a one-size-fits-all approach is not suitable. Therefore, our lab employs an integrative and multidisciplinary approach to investigate astrocyte-interneuron crosstalk, aiming to elucidate how disruptions in this interaction contribute to synaptic imbalance.

A missing key: Synaptic balance

In the last two decades, numerous astrocyte-secreted factors controlling excitatory (glutamatergic) neuron development and excitatory synaptogenesis have been identified. However, the identity of astrocyte-secreted factors controlling inhibitory (GABAergic) neuronal growth, maturation, and inhibitory synaptogenesis remains largely unknown. We recently identified that astrocytes specifically regulate somatostatin+ inhibitory synapse formation and function through secretion signals. Our results unveiled a novel mechanism through which astrocytes control circuit-specific inhibitory synapse development in the mammalian brain.

To continue exploring the role of astrocytes during inhibitory synaptogenesis and synaptic balance, we are now interested in dissecting the cellular and molecular mechanisms that astrocytes utilize to trigger different inhibitory synaptic contacts and neuronal growth. Our long-term goal is to elucidate how neuron-astrocyte communication shapes brain connectivity. Thus, by understanding the driving forces that rule brain development, we can design therapeutic approaches for neurodevelopmental disorders.

Our approach

The laboratory utilizes a wide variety of cellular and molecular techniques, including super-resolution microscopy, electron microscopy, cell culture, human brain organoids, and omics. And while our investigation is rooted in basic science—uncovering the cellular and molecular underpinnings of astrocyte-neuron communication in health and disease—our vision is to develop novel therapeutic strategies for neurological disorders.