Switching of the transmitters that mediate hindbrain correlated activity in the chick embryo

Abstract

Widely propagating correlated neuronal activity is a hallmark of the developing nervous system. The activity is usually mediated by multiple transmitters, and the contribution of gap junctions has also been suggested in several systems. In some structures, such as the retina and spinal cord, it has been shown that the dominant transmitter mediating the correlated wave switches from acetylcholine to glutamate during development, although the functional significance of this phenomenon has not been clarified. An important question is whether such a transmitter switch occurs in other systems, especially in the brain. In the present study, we demonstrate that the major transmitter mediating correlated wave activity in the embryonic chick hindbrain changes from acetylcholine/gamma-aminobutyric acid (GABA)/glycine to glutamate/GABA as development proceeds. The results show for the first time that the dominant transmitter switches from acetylcholine to glutamate in a region other than the retina and spinal cord. This finding sheds more light on the role of nicotinic acetylcholine receptors in the generation of correlated wave activity, which is considered to regulate the development of the nervous system.

Properties and mechanisms of spontaneous activity in the embryonic chick hindbrain

“…Preliminary experiments using spinal cord-hindbrain preparations suggest that this dependence remains in this more intact preparation (Easton and Bosma, unpublished results). Changes in pharmacological dependence over development of the chick hindbrain has recently been shown by Mochida et al, 2009, where the influence of ACh decreases as GABAergic input becomes more important. Our pharmacology was conducted at E6, where both inputs were shown to be important.…”

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

“…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).…”

“…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). Despite these data, the cellular signals that govern the early specification of NT systems and the role of spiking behavior in this process are still incomplete.…”

“…Despite these data, the cellular signals that govern the early specification of NT systems and the role of spiking behavior in this process are still incomplete. Moreover, a hallmark of rSNA, as well as other forms of correlated neuronal activity, is the ability of the underlying interneuronal circuits to adapt to changes in synaptic input ( e.g ., synaptic depression/augmentation) to maintain appropriate levels of excitability (Momose-Sato and Sato, 2013). While several studies show that early neuronal circuits can regain function in the face of synaptic imbalance, there is a poverty of information on the mechanisms that provide neurotransmitter phenotypic stability in the context of potentially dangerous environmental influences experienced by human embryos.…”

“…Yet, a direct connection between nicotine-induced elimination of spontaneous bursting and the potentiation of GABAergic and glycinergic NT has not been established. Moreover, how early brainstem circuits respond to persistent nicotine insults is completely unknown, especially at a chronological stage where nicotinergic NT is a principal driver of rSNA (Mochida et al, 2009). In addition, while early rSNA is considered a widespread intersegmental wave, data show that different regions of the CNS exhibit unique patterns of rSNA activity (Fortin et al, 1995) and nicotinic receptor expression (Hughes et al, 2009).…”