Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABA_A and GABA_B receptors

Abstract

GABA is the most abundant neurotransmitter in the circadian pacemaker circuits of mammals and insects. In the Madeira cockroach the accessory medulla (AME) in the brain′s optic lobes is the circadian clock that orchestrates rest‐activity rhythms in synchrony with light dark cycles. Three prominent GABAergic tracts connect the AME to termination sites of compound eye photoreceptors in the lamina and medulla. Parallel GABAergic light entrainment pathways were suggested to either advance or delay the clock for adjustment to changing photoperiods. In agreement with this hypothesis GABA activated or inhibited AME clock neurons, allowing for the distinction of three different GABA response types. Here, we examined which GABA receptors are responsible for these response types. We found that both ionotropic GABAA receptors and metabotropic GABAB receptors were expressed in AME clock cells. Via different signalling pathways, either one of them could account for all three GABA response types. The muscimol‐dependently activated GABAA receptor formed a chloride channel, while the SKF 97541‐dependently activated GABAB receptor signalled via G‐proteins, apparently targeting potassium channels. Expression of chloride exporters or importers determined whether GABAA receptor activation hyper‐ or depolarized AME neurons. For GABAB receptor responses second messenger gated channels present in the clock cells appeared to decide about the polarity of the GABA response. In summary, circadian clock neurons co‐expressed inhibitory and/or excitatory GABAA and GABAB receptors in various combinations, while cotransporter expression and the set of second messenger gated ion channels present allowed for distinct signalling in different clock neurons.

Circadian regulation of membrane physiology in neural oscillators throughout the brain

“…More recent work has shown specifically that the accessory medulla of the optic lobe is critical for nocturnal behavior such that electrical recordings from this region show rapid increases in electrical activity more frequently at night (Schneider & Stengl, ). Neurophysiological activity of clock neurons in these invertebrates is inhibited or excited by GABA (see Giese, Wei, & Stengl, in this Special Issue) similar to results reported in vertebrate clocks, where GABA is involved in entrainment and synchronization (Albers, Walton, Gamble, McNeill, & Hummer, ). Invertebrate electrical rhythms may be important for learning given that these cockroaches are better at olfactory learning and recall during the night phase compared to during the day (Decker, McConnaughey, & Page, ).…”

Lamina feedback neurons regulate the bandpass property of the flicker‐induced orientation response in Drosophila

“…However, we found dose‐dependent calcium increases in L1/L2 after GABA bath application. Several studies have reported excitatory GABA effects, both in mammals and in insects, either via chloride‐gradient‐dependent GABAa receptors or metabotropic GABAb receptors (Giese, Wei, & Stengl, 2018; Haam et al., 2012; Kobayashi, Matsuo, Sadamoto, Watanabe, & Ito, 2012). Hardie (1987) demonstrated acetylcholine could depolarize the lamina monopolar neurons in houseflies.…”

“…GABAa receptors or metabotropic GABAb receptors (Giese, Wei, & Stengl, 2018;Haam et al, 2012;Kobayashi, Matsuo, Sadamoto, Watanabe, & Ito, 2012). Hardie (1987) demonstrated acetylcholine could depolarize the lamina monopolar neurons in houseflies.…”

The opposing Chloride Cotransporters KCC and NKCC control locomotor activity in constant light and during long days

“…In cockroaches, circadian neurons have been found to exert both inhibitory and excitatory responses to GABA, depending on the balance of NKCC1 / KCC2 activity. About 50% of all cockroach clock neurons respond to GABA, and about 30% of all GABA-responsive neurons show an increase of [Ca 2+ ] i as GABA response, which was correlated with enhanced NKCC expression compared to KCC 15 . In the mammalian brain clock, the suprachiasmatic nucleus (SCN), expression and activity of the two opposing cotransporters NKCC1 and KCC2 underlie daily and regional variation.…”