Properties and mechanisms of spontaneous activity in the embryonic chick hindbrain

Abstract

Spontaneous activity regulates many aspects of central nervous system development. We demonstrate that in the embryonic chick hindbrain, spontaneous activity is expressed between embryonic days (E) 6-9. Over this period the frequency of activity decreases significantly, although the events maintain a consistent rhythm on the timescale of minutes. At E6, the activity is pharmacologically dependent on serotonin, nACh, GABA(A), and glycine input, but not on muscarinic, glutamatergic, or GABA(B) receptor activation. It also depends on gap junctions, t-type calcium channels and TTX-sensitive ion channels. In intact spinal cord-hindbrain preparations, E6 spontaneous events originate in the spinal cord and propagate into lateral hindbrain tissue; midline activity follows the appearance of lateral activity. However, the spinal cord is not required for hindbrain activity. There are two invariant points of origin of activity along the midline, both within the caudal group of serotonin-expressing cell bodies; one point is caudal to the nV exit point while the other is caudal to the nVII exit point. Additional caudal midline points of origin are seen in a minority of cases. Using immunohistochemistry, we show robust differentiation of the serotonergic raphe near the midline at E6, and extensive fiber tracts expressing GAD65/67 and the nAChR in lateral areas; this suggests that the medial activity is dependent on serotonergic neuron activation, while lateral activity requires other transmitters. Although there are differences between species, this activity is highly conserved between mouse and chick, suggesting that developmental event(s) within the hindbrain are dependent on expression of this spontaneous activity.

The assembly of developing motor neurons depends on an interplay between spontaneous activity, type II cadherins and gap junctions

“…The activity we describe might also regulate neuronal maturation and the acquisition of afferent input, which may include descending input from early longitudinal tracts and the vestibular and raphe spinal systems (Gilland and Baker, 2005;Hughes et al, 2009). The link between motor nucleogenesis and brainstem neuronal circuit formation remains to be characterised.…”

Activity-dependent plasticity in the isolated embryonic avian brainstem following manipulations of rhythmic spontaneous neural activity

“…The in utero exposure to nicotine in human embryos contributes to significant neonatal mortality and leads to substantial medical expenses worldwide each year (Aligne and Stoddard, 1997; Bank, 1999; Wickström, 2007). Previous studies examining the effects nicotinic neurotransmitter signaling on the embryonic chick lumbar spinal cord show that low doses of nicotine (0.1–1 µM) eliminates rSNA by overexciting the network and desensitizing nAChRs (Hughes et al, 2009; Milner and Landmesser, 1999). Moreover, several experiments suggest that nicotinic NT can increase GABA and glycine release onto spinal motoneurons via Renshaw cell activity (Gonzalez-Islas et al, 2016) and can even drive rSNA in the absence of normal excitatory NT, for example, following the bath application of a glutamate and cholinergic blocker cocktail (Chub and O’Donovan, 1998).…”

“…For example, both the presence and pattern of rSNA has been shown to influence neuronal migration, axon guidance, expression of individual ion channels, and neurotransmitter phenotypes in the CNS (Borodinsky et al, 2013; Chub and O’Donovan, 1998; Hanson and Landmesser, 2006; Spitzer, 2012; Wenner, 2013; Yoon et al, 2010, 2008). When examining the isolated neuraxis in vitro , rSNA is expressed as periodic episodes of recurrent spike train activity initiated in the hindbrain and or the spinal cord, depending on developmental stage, which then propagates from these initiation zones both rostrally and caudally to the forebrain and the sacral spinal cord, respectively (Hughes et al, 2009; Momose-Sato and Sato, 2014). In the chick brainstem, rSNA is first revealed by synchronous cranial motor output immediately following rhombomeric segmentation near embryonic day four (Lumsden and Keynes, 1989; Fortin et al, 1995, 1994).…”

“…In the chick brainstem, rSNA is first revealed by synchronous cranial motor output immediately following rhombomeric segmentation near embryonic day four (Lumsden and Keynes, 1989; Fortin et al, 1995, 1994). Once rSNA begins in the hindbrain, data show that excitation is generated as single electrical episodes (Fortin et al, 1994, 1995, 1999) and is critically dependent on nicotinergic neurotransmission (NT) with weaker modulatory contributions from neurons that release GABA (γ-aminobutyric acid) and glycine (Hughes et al, 2009; Mochida et al, 2009). As development proceeds, the central episodes become more complex, i.e ., single episodes with multiple bursts, and the dominant neurotransmitter system that drives rSNA transforms from chiefly nicotinergic NT to a combination of GABA, glycine and glutamate NT (Mochida et al, 2009).…”

Perchance to dream? Primordial motor activity patterns in vertebrates from fish to mammals: their prenatal origin, postnatal persistence during sleep, and pathological reemergence during REM sleep behavior disorder

“…The vigor and extent of muscular activity and its widespread neurological substrate in prenatal animals [39][40][41][42] call for a distinctive terminology, such as 'rapid-BODY- A striking example of this continuity is the preservation throughout life of the stochastic and rhythmical nature of fetal spontaneous motility [10,43,44] . This implies that subliminal excitatory fl uctuations may still be taking place within the spinal cord and medulla oblongata, needing now only to receive adequate stimulation from the pontine trigger zone [6,7,45] in order to once again reach threshold for effectively evoking motoneuron discharges, as has been nicely demonstrated in chick and mouse embryos [46,47] .…”