Multiple functions of GABA_A and GABA_B receptors during pattern processing in the zebrafish olfactory bulb

Abstract

gamma-Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in the processing of activity patterns in the olfactory bulb (OB), but their functions have been difficult to study during odor responses in the intact system. We pharmacologically manipulated GABA(A) and GABA(B) receptors in the OB of zebrafish and analysed the effects on odor responses of the output neurons, the mitral cells (MCs), by electrophysiological recordings and temporally deconvolved two-photon Ca2+ imaging. The blockade of GABA(B) receptors enhanced presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude and time course of a subset of MC responses, indicating that GABA(B) receptors have a modulatory influence on OB output activity. The blockade of GABA(A) receptors induced epileptiform firing, enhanced excitatory responses and abolished fast oscillations in the local field potential. Moreover, the topological reorganization and decorrelation of MC activity patterns during the initial phase of the response was perturbed. These results indicate that GABA(A) receptor-containing circuits participate in the balance of excitation and inhibition, the regulation of total OB output activity, the synchronization of odor-dependent neuronal ensembles, and the reorganization of odor-encoding activity patterns. GABA(A) and GABA(B) receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB.

Acid–base physiology, neurobiology and behaviour in relation to CO2-induced ocean acidification

“…This is an interesting point because gabazine should also affect normal inhibitory GABA regulation, inducing neuronal excitation; in fact, one of the features precluding the use of gabazine as a therapeutic agent in humans is the risk of convulsions resulting from inappropriate neuronal excitation (Enna and Bowery, 1997). A similar effect was seen in intact zebrafish (Danio rerio) brains, where gabazine increased the spontaneous firing rate of olfactory neurons, altered the dynamics of odour-induced firing, blocked fast oscillatory synchronization of local neurons and induced epileptiform activity (Tabor et al, 2008).…”

Fast gene transfer into the adult zebrafish brain by herpes simplex virus 1 (HSV-1) and electroporation: methods and optogenetic applications

“…In order to produce large changes in intracellular calcium concentration we applied the GABA A receptor blocker Gabazine (1 μM) through the bath. This treatment is known to induce epileptiform bursting of many neurons in the forebrain at low inter-burst frequency (Tabor et al, 2008). Gabzine induced large changes in fluorescence intensity (ΔF/F) throughout the soma and dendrites of many GECI-expressing cells that occurred at frequencies of approximately 0.1–0.3 Hz (Figures 5A–C).…”

Cloning of the GABAB Receptor Subunits B1 and B2 and their Expression in the Central Nervous System of the Adult Sea Lamprey

“…Expression of GABA B receptors has been reported in olfactory sensory neurons of moths (Pregitzer et al, 2013) and in the entire CNS of cockroaches (Blankenburg et al, 2015), spiders (Panek et al, 2003) and Drosophila melanogaster (Mezler et al, 2001). The expression of GABA B transcripts (GABA B1 and GABA B2 ) has been also reported in a few jawed vertebrate species (rats: Bischoff et al, 1999; Fritschy et al, 1999; humans: Calver et al, 2000; Berthele et al, 2001; non-human primates: Muñoz et al, 1998, 2001; zebrafish: Tabor et al, 2008; and frogs: Kaeser et al, 2011). These studies reveal a wide distribution of this receptor in the entire CNS of invertebrate and vertebrate species.…”

“…All brain regions and the spinal cord showed a broad expression of both GABA B transcripts in the adult sea lamprey, which is in concordance with previous reports in invertebrates (e.g., D. melanogaster (Mezler et al, 2001), cockroaches (Blankenburg et al, 2015) or spiders (Panek et al, 2003)) and in jawed vertebrates (e.g., humans (Calver et al, 2000; Berthele et al, 2001), non-human primates (Muñoz et al, 1998; Nürnberger and Schöniger, 2001), rats (Bowery et al, 1987; Bischoff et al, 1999; Clark et al, 2000), birds (Veenman et al, 1994), frogs (Kaeser et al, 2011) and zebrafish (Tabor et al, 2008; Cocco et al, 2016)). Positive in situ signal in sea lamprey brain sections had a granular appearance probably due to low expression of these mRNAs in each single cell of the sea lamprey.…”