Early activity in the developing brain

RUSTEM KHAZIPOV & MARAT MINLEBAEV

Early research into the activity patterns of developing neuronal networks relied on ex vivo preparations from neonatal rodents. These studies revealed spontaneous network bursts—such as hippocampal Giant Depolarizing Potentials (GDPs) and early network oscillations—and helped identify their underlying mechanisms (Ben-Ari et al., 2007; Khalilov et al., 2015; Leinekugel et al., 1997). However, the physiological relevance of these patterns to neonatal brain activity in vivo remained unclear. To bridge this gap, we developed a platform combining multisite intracortical silicon probe recordings and patch-clamp techniques in neonatal rats. This allowed us to characterize activity patterns expressed in vivo, including early sharp waves (eSPWs) in the hippocampus (Leinekugel et al., 2002). These eSPWs are triggered by spontaneous movements and involve activation of the entorhinal cortex (Valeeva et al., 2019). Using this approach, we also identified movement-driven oscillatory patterns in the primary somatosensory cortex (S1) and thalamus (Akhmetshina et al., 2016; Khazipov et al., 2004; Minlebaev et al., 2011) and in the spinal cord (Inacio et al., 2016). Similarly, we observed bursts driven by retinal waves  in the visual cortex (Colonnese et al., 2010; Colonnese & Khazipov, 2010; Hanganu et al., 2006). Two-photon imaging has revealed synchronized activity even earlier in development, in the embryonic mouse cortex (Yuryev et al., 2018). Further translation of these findings to the human neonates resulted in elaboration of protocols of sensory exploration of the neonate in different sensory modalities (somatosensory, visual and auditory), that was achieved through long-standing collaboration with the group of Anna Kaminska at Necker Hospital (Paris) (Chipaux et al., 2013; Colonnese et al., 2010; Kaminska et al., 2018; Milh et al., 2007).

Rustem Khazipov & Ilgam Khalilov

Our previous studies identified instrumental roles for depolarizing and excitatory actions exerted by GABA on immature neurons, and synergistic actions of GABA and glutamate In GDPs generation in vitro (Ben-Ari et al., 2007; Khalilov et al., 2015; Leinekugel et al., 1997). Various aspects of depolarizing GABA actions on immature neurons have been characterized including the oxytocin mediated perinatal switch in GABA actions, dualism and dynamic activity-dependent changes in GABA actions at the network level (Khalilov et al., 1999; Khalilov et al., 2017; Tyzio et al., 2006; Valeeva et al., 2010). Yet, these findings were mainly obtained using in vitro preparations of brain slices or intact preparations in vitro. Explorations in the Intact brain of neonatal rodents in vivo yielded different results compatible with rather inhibitory than excitatory actions of GABA (Colonnese et al., 2010; Minlebaev et al., 2007; Valeeva et al., 2016). Interestingly, depolarizing shifts in GABA reversal potential and acquisition of the “immature” excitatory GABA phenotype have also been suggested to participate in various disease models Including epilepsy (Dubanet et al., 2021b; Khalilov et al., 2003; Kourdougli et al., 2017; Nardou et al., 2009; Pallud et al., 2014) and brain trauma (Dzhala et al., 2012; Goubert et al., 2019). These changes in GABA actions were associated with down-regulation of KCC2-mediated chloride extrusion, and could be partly restored using selective blocker of chloride-loading NKCC1 co-transporter bumetanide. Nevertheless, as regarding development, the relevance of excitatory GABA in these pathological conditions in vivo is still a matter of active debate, and was not confirmed by the only direct investigation performed in vivo, using the methodology developed by our group (Dubanet et al., 2021b).

JÉRÔME LAURIN, CLAUDIO RIVERA & CHRISTOPHE PELLEGRINO

The present research topic focuses on the impact of different endurance exercises on cortical and hippocampal functions, as well as on cognitive and sensorimotor functions, in healthy subjects (both young and elderly) and those who have suffered a stroke. The proposed approach to this subject involves the utilisation of multidisciplinary measures across diverse study models, encompassing behavioural (sensorimotor, cognitive, depressive state), molecular (to delineate the molecular signatures of each training method), and electrophysiological (to facilitate a more functional approach) domains.

It is the objective of this study to define the role of the major molecular players in brain plasticity, with a particular focus on neurotrophic factors, their interaction with chloride ion co-transporters, and neurogenesis. This objective is based on the following different measures. Lactate and myokines represent two of the factors involved in brain plasticity, which are being used in order to identify the mechanisms specific to each training method, thus justifying their specific benefits.