Investigating the Molecular identity of PAcemaker neurons in CorTical development

Spontaneous activity is a prominent feature of the immature brain.

Even before birth and in absence of stimuli, neurons organize in networks and spontaneously generate correlated activity.

While spontaneous dynamics in the cerebral cortex have long been overlooked and considered just as epiphenomena, recent clinical data on preterm infants and preclinical studies have spurred a renewed interest for this early electrical activity. However, appreciation of the role of spontaneous activity during the perinatal stages remains elusive.

Indeed, it is still unknown how spontaneous patterns arise, and whether, among the large variety of neuronal classes generated in the cerebral cortex, distinct subtypes can act as pacemaker (Pm) neurons, able to trigger some of these events.

Defects arising from alterations in the early cortical spontaneous activity have never been thus far systematically addressed, yet they can affect local assembly and physiological behavioural states.The IMPACT project aims to shed light on how cortical neuronal diversity influences early spontaneous activity, and to identify the molecular features and functional role of developing Pm neurons.

By integrating innovative molecular strategies with in vivo optical recordings and behavioural assays, I will 1) characterise and spatially resolve the subtype-specific molecular footprints correlated with electrical profiles of neuron subtypes, with a special focus on Pm neurons; 2) assess molecular, cellular and circuit consequences of perturbations in Pm neuron activity; 3) identify novel functional modulators of Pm activity in the surrounding cerebrospinal fluid (CSF) around birth.

IMPACT bears the ambition of filling the knowledge gap between the molecular and functional traits of developing cortical neurons, while unveiling the existence and critical role of the Pm neurons.

Discovering new molecular players and modulators of early activity will inspire novel intervention strategies for perinatal disorders.