3.5.1 Neurotransmission
A range of genes and functional categories involved in various types of neurotransmission were significantly affected by COtreatment (Table 2). We identified small, coordinated downregulation of genes belonging to a cluster of nine functional categories in the CNS, and upregulation of two functional categories in the eyes, involved in ligand-gated ion channel-mediated neurotransmission. The genes contributing most to the up-/down-regulation of each of these functional categories (core enrichment genes) in the CNS and eyes included genes for components of acetylcholine, GABAA and glutamate ion channel receptors (Table S11). There was also small, coordinated downregulation in the CNS of genes belonging to two functional categories involved in G protein-coupled receptor (GPCR)-mediated neurotransmission, including genes coding for components of metabotropic glutamate, GABAB, serotonin and dopamine receptors (Table S12). Notably, a subunit of nicotinic acetylcholine receptors (chrna10) was correlated with CO2 treatment and behaviours in both tissues. Chrna10 as well as other genes coding for nicotinic acetylcholine receptor subunits (chrna1chrna3, chrna5, and chrnb1) were core enrichment genes in eight functional categories significantly affected by CO2 treatment in both tissues. Genes coding for regulation of GABAergic neurotransmission were upregulated in both tissues (CNS: syvn1-b, eyes: slc18a2), and positively correlated with CO2 treatment and behaviours in the CNS (phf24, rac1), while aldh5a1, which is involved in the final degradation step of GABA (Kim et al. , 2009), was negatively correlated with CO2 treatment and behaviours in the CNS. Furthermore, there was upregulation of folh1(glutamate synthesis) and downregulation of celsr3 (mediator of glutamatergic synapse formation) in the CNS. There was also upregulation in the eyes of two key genes involved in monoaminergic (dopamine, serotonin (5-HT), norepinephrine, and epinephrine) neurotransmission (maoa, slc18a2).
Genes involved in the general processes required for synaptic neurotransmission also displayed altered expression after elevated CO2 exposure (Table 2). There was small, coordinated downregulation in the CNS of genes belonging to a cluster of seven functional categories involved in K+, Ca2+ and Na+ ion transport important for general processes involved in neurotransmission, including maintenance of membrane potential, action potential generation and neurotransmitter release (Table S13). Furthermore, genes involved in regulating synaptic neurotransmission (futsch, dgkq) were negatively correlated with CO2 treatment and activity traits in the CNS.