The ability to generate primitive patterns of spontaneous activity is a well preserved feature of immature central nervous system (CNS) networks. From the retina to the hindbrain or the spinal cord, synchronized episodes of activity take place primarily or exclusively during restricted windows of time and are globally similar among different structures during intense synaptogenesis or growth (O’Donovan, 1999; Ben-Ari, 2001; Moody & Bosma, 2005). Recurrent activity often propagates allowing contiguous structures to perform as an ensemble (Feller, 1999). The slow propagation of this activity usually follows a precise spatial distribution that changes over the course of development (Ben-Ari, 2001; Gust et al. 2003). Although the roles of this activity during ontogenesis remain mostly unresolved, one traditional view is that it contributes to the activity-dependent developmental organization of neuronal circuits with specific functions (Feller, 1999; Ben-Ari, 2001; Moody & Bosma, 2005). In the mouse embryonic hindbrain, endogenous neuronal domains have been suggested to lead spontaneous activity underlying intracellular calcium transients, since these episodes are recorded in whole hindbrain or slice preparations, deprived of influences from other CNS regions (Gust et al. 2003). Synchronized activity originates from midline neurons and propagates laterally (Gust et al. 2003; Moruzzi et al. 2009), and such a spontaneous activity eventually disappears at later stages of CNS development. It has been suggested that a differential expression of peculiar intrinsic properties consistently, yet only transiently, confer to midline neurons the ability to initiate episodes of activity. Certainly to appreciate how spontaneous activity shapes hindbrain embryonic circuits requires an understanding of the mechanisms which confer to primitive events certain spatial correlations. Such mechanisms may rely on single neuronal electrophysiological properties. Do midline neurons possess intrinsic features or voltage-dependent conductances that would endow them with the ability to drive activity in the developing hindbrain? In this issue of The Journal of Physiology, Moruzzi et al. (2009) provide evidence supporting the hypothesis that a combination of low gap-junctional coupling, T-type calcium channels and high input resistance underpins the ability of midline neurons to drive primitive episodes of activity in the immature hindbrain rostral circuits. In accordance with previous studies, the authors confirmed the correlation between spontaneous electrical events and calcium events within the isolated embryonic hindbrain. Electrical events consist of slow graded depolarisations that, as assessed by dual patch clamp recordings, originate near the midline and propagate towards lateral regions. Using pipettes filled with neurobiotin (a widely used tracer in neurobiology) they marked cell positions, and the electrophysiological properties recorded from each neuron were plotted on a functional map relative to the midline region. The shape of the depolarizing events varies by region, in particular in the peak amplitude and duration of both initial spike and plateau components of the biphasic event. Lateral events are usually slower and smaller. Investigating the extent of dye coupling after recordings performed with neurobiotin-filled electrodes reveals the presence of a differential gap junction coupling. Confocal microscopy assessment of clusters of neurobiotin-coupled neurons shows a medio-lateral distribution of coupling. Lateral tissue, displaying lower and slower depolarizing events, is significantly more coupled via neurobiotin-permeant gap junctions. The direct consequence of the higher coupling is that lateral cells are more ‘leaky’, less excitable, an evidence supported by the medio-lateral spatial variation in resting leak conductance. The medial tissue lower gap junctional coupling is reflected in larger and faster electrical events, more prone to initiate spontaneous activity. In addition, medial cells possess inward T-type currents that correlate with the ability to express the rapid spike component of the spontaneous events, absent in lateral neurons. The driving of spontaneous activity at the midline is transient and may reinforce the ability of differentiating or migrating cells to sense medio-lateral position, playing a role in decision-making near the midline. It will be important in future studies to identify other ion channels responsible for the changes, during subsequent developmental stages, of the medial and lateral neuron activity profile and how this influences the behaviour of hindbrain networks.
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Jun 12, 2023
Lujain Alaali + 5
Open Access
