GABA_B receptor expression and function in olfactory receptor neuron axon growth

Abstract

Neurotransmitters have been implicated in regulating growth cone motility and guidance in the developing nervous system. Anatomical and electrophysiological studies show the presence of functional GABAB receptors on adult olfactory receptor neuron (ORN) nerve terminals. Using antisera against the GABAB R1a/b receptor isoforms we show that developing mouse olfactory receptor neurons express GABAB receptors from embryonic day 14 through to adulthood. GABAB receptors are present on axon growth cones from both dissociated ORNs and olfactory epithelial explants. Neurons in the olfactory bulb begin to express glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, from E16 through to adulthood. When dissociated ORNs were cultured in the presence of the GABAB receptor agonists, baclofen or SKF97541, neurite outgrowth was significantly reduced. Concurrent treatment of the neurons with baclofen and the GABAB receptor antagonist CGP54626 prevented the inhibitory effects of baclofen on ORN neurite outgrowth. These results show that growing ORN axons express GABAB receptors and are sensitive to the effects of GABAB receptor activation. Thus, ORNs in vivo may detect GABA release from juxtaglomerular cells as they enter the glomerular layer and use this as a signal to limit their outgrowth and find synaptic targets in regeneration and development.

Two GABAergic Intraglomerular Circuits Differentially Regulate Tonic and Phasic Presynaptic Inhibition of Olfactory Nerve Terminals

“…In addition, ON terminals express GABA B receptors (Bonino et al 1999;Kratskin et al 2006;Priest and Puche 2004) Koster et al 1999;Maher and Westbrook 2008;Parrish-Aungst et al 2007;Wachowiak and Cohen 1999). Thus ON-evoked PPD can be due to at least two distinct presynaptic mechanisms: reduced vesicle availability and transmitter release due to the high release probability of ON terminals and presynaptic inhibition via activation of GABA B Rs and/or DA D 2 Rs on ON terminals.…”

Non-hyperpolarizing GABAB receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1

“…Despite the extensive literature on the importance of GABA A R during early development 1,2,6,7,9 , the role of GABA B R has been poorly investigated and data are controversial 10 . For example, a role of GABA B R in neuronal morphological maturation was described in some systems 9,11,12 , but not in others 13 , and only in vitro evidence indicated that GABA B R modulates migration of immature neurons [14][15][16][17] . Furthermore, these in vitro data are in contrast with observations in a number of mouse strains genetically modified for GABA B Rs, which present grossly normal brain and cell morphology [18][19][20][21][22][23][24][25][26] .…”

The Activation of M1Muscarinic Receptor Signaling Induces Neuronal Differentiation in Pyramidal Hippocampal Neurons

“…Glutamate, acting through N-methyl-D-aspartate receptors, induces neurite outgrowth in hippocampal neurons (Mattson et al, 1988) and cerebellar granule cells (Pearce et al, 1987). GABA promotes neurite outgrowth in rat cerebellar neurons (Michler, 1990), rat hippocampal neurons (Barbin et al, 1993), and rat olfactory bulb neurons cocultured with astrocytes (Matsutani and Yamamoto, 1998) via activation of GABA A receptors and of mouse olfactory receptor neurons (Priest and Puche, 2004) via GABA B receptors. Together, these observations strongly suggest that neurotransmitters, including acetylcholine, may play an important role during brain development and, particularly, in neurite outgrowth.…”