Evolutionary aspects of neural mechanisms underlying respiratory rhythm generation in vertebrates

The lamprey, which diverged from the main vertebrate line around 560 million years ago, proved to be highly useful to identify neuronal circuits underlying rhythmic motor behaviours, such as locomotion and respiration. The isolated brainstem of the adult lamprey spontaneously generates rhythmic respiratory activity in vitro. The respiratory central pattern generator (CPG) is located in the paratrigeminal respiratory group (pTRG), a region rostral to the trigeminal motor nucleus. The pTRG shows many similarities with the preBötzinger Complex (preBötC), the proposed mammalian inspiratory CPG. It is well known that ATP plays a role in the control of the preBötC and that astrocytes contribute to purinergic modulation. Recently, this issue has been investigated also in the lamprey. The results show for the first time that astrocytes strongly contribute to the maintenance of the activity of the pTRG via the glutamate-glutamine cycle. In addition, they are involved in the genesis of ATPinduced increases in respiratory frequency at the pTRG level. Acidification evokes ATP-independent increases in the respiratory motor output that requires astrocyte metabolic support. Another important neuromodulator of the preBötC is serotonin (5-HT). In the adult rabbit, 5-HT has been shown to play a pivotal role, especially through a 5-HT1A receptor-mediated inhibition of GABAergic inhibitory interneurons. The existence of a similar mechanism mediated by both GABAergic and glycinergic neurons has also been shown at the pTRG level. The results support the notion that some important features of the neural circuit underlying respiratory rhythm generation are highly conserved throughout phylogeny.