3.5.1 Neurotransmission
A range of genes and functional categories involved in various types of
neurotransmission were significantly affected by CO2 treatment (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 (chrna1, chrna3, 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.