Prenatal thalamic waves regulate cortical area size prior to sensory processing

Abstract

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing.

Functional properties of habenular neurons are determined by developmental stage and sequential neurogenesis

“…Activity-dependent maturation of neural circuits, do not solely rely on sensory inputs but also include endogenously generated spontaneous activity (Penn and Shatz, 1999). In several brain regions spontaneously generated activity is thought to play important roles in the maturation of synaptic connections, refining network topography (Katz and Shatz, 1996;Moreno-Juan et al, 2017;Xu et al, 2011) and entraining developing circuits (Clause et al, 2014;Gretenkord et al, 2019;Huberman et al, 2006). In our study, we observed that habenular networks exhibit spatially organized spontaneous activity already at early developmental stages.…”

“…In the cortex for example, individual layers are born at different time points, with deep layers being born earlier than superficial layers (Angevine and Sidman, 1961;Lein et al, 2017;Luskin and Shatz, 1985), creating a diversity in the cytoarchitecture of cortical layers, cell types and regions with distinct functions (Donato et al, 2017;Jabaudon, 2017;Sur and Leamey, 2001). The maturation and refinement of the developing brain relies on neural activity, which can be evoked by sensory inputs (Penn and Shatz, 1999;Wiesel and Hubel, 1965), or spontaneously generated (Galli and Maffei, 1988;Moreno-Juan et al, 2017;O'Donovan, 1989;Penn and Shatz, 1999;Yuste, 1997). In most sensory systems, sensory evoked activity was shown to be critical for the maturation of neural circuits and the refinement of topographical maps (Katz and Shatz, 1996;Webster and Webster, 1977;White et al, 2001;Wiesel and Hubel, 1965;Zou et al, 2004).…”

“…The appearance of spontaneous activity of the developing brain starts early, and coincides with periods of intense synaptogenesis and neuronal growth (Ben-Ari, 2001;Galli and Maffei, 1988;Maffei and Galli-Resta, 1990). For example, spontaneous activity bursts were observed in the visual, auditory and somatosensory systems (Elstrott et al, 2008;Feller, 1999), and are shown to be important for the remodelling of these structures (Katz and Shatz, 1996;Moreno-Juan et al, 2017;Xu et al, 2011). In higher brain regions, such as the hippocampus, large and slow bursts are observed (Leinekugel et al, 1998;Rudy et al, 1987) before the appearance of faster rhythms and the patterned activity of the adult hippocampus associated with learning and memory (Altman et al, 1973;Rudy et al, 1987).…”

Spatiotemporal dynamics of calcium transients during embryogenesis of Drosophila melanogaster

“…Intercellular calcium waves transmit local information from the initiator cell to a large number of cells in order to coordinate and synchronize their activity during development (Moreno-Juan et al, 2017;Akahoshi , Hotta and Oka 2017, Wallingford et al 2001, Webb and Miller 2003, Özsu and Monteiro 2017. Surprisingly, endogenous calcium waves during embryogenesis of insects have not been documented.…”

Anatomical development of the cerebellothalamic tract in embryonic mice

“…Some sparse reports on a developing CbT tract in the post-natal opossum (Martin et al, 1987), rat (Cholley et al, 1989;Shirasaki et al, 1995) and a single report in mouse embryo (Hara et al, 2016) describe the timing of CN innervation of midbrain nuclei, such as the parabrachial and red nuclei, and subsequently commence to the thalamic primordium, but no data on the ontogeny of cerebellar innervation of the thalamic complex is currently available. Given that early synaptic afferents have recently been shown to modulate thalamic activity patterns, gene expression profiles and the thalamocortical connectivity (Mire et al, 2012;Chou et al, 2013;Moreno-Juan et al, 2017) it is of utmost importance to elucidate at what embryonic stage cerebellar axons start to innervate the developing thalamus. The cerebellum is especially important in this regard, given that in the adult rodent the CbT tract diverges to many first-order and higher-order nuclei, including ventrolateral (VL), ventromedial (VM), centrolateral (CL), posteriomedial (POm), parafascicular (Pf) and mediodorsal (MD) (Bentivoglio and Kuypers, 1982;Shinoda et al, 1985;Sawyer et al, 1994;Teune et al, 2000;Gao et al, 2018;Gornati et al, 2018) each of which has critical periods for growth and maturation of its afferents and efferents.…”