Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA(B) heteroreceptors

Olfactory receptor neurons of the nasal epithelium send their axons, via th e olfactory nerve (ON), to the glomeruli of the olfactory bulb (OB), where the axon terminals form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the OB, and with juxtaglomeru lar (JG) interneurons. Many JG cells are GABAergic. Here we show that, desp ite the absence of conventional synapses, GABA released from JG cells activ ates GABA(B) receptors on ON terminals and inhibits glutamate release both tonically and in response to ON stimulation. Field potential recordings and current-source density analysis, as well as intracellular and whole cell r ecording techniques were used in rat OB slices. Baclofen (2-5 mu M), a GABA (B) agonist, completely suppressed ON-evoked synaptic responses of both mit ral/tufted cells and JG cells, with no evidence for postsynaptic effects. B aclofen (0.5-1 mu M) also reversed paired-pulse depression (PPD) of mitral/ tufted cell responses to paired-pulse facilitation (PPF), and reduced depre ssion of JG cell excitatory postsynaptic currents (EPSCs) during repetitive ON stimulation. These results suggest that baclofen reduced the probabilit y of glutamate release from ON terminals. The GABA(B) antagonists CGP35348 or CGP55845A increased mitral/tufted cell responses evoked by single-pulse ON stimulation, suggesting that glutamate release from ON terminals is toni cally suppressed via GABA(B) receptors. The same antagonists reduced PPD of ON-evoked mitral/tufted cell responses at interstimulus intervals 50-400 m s. This finding suggests that a single ON impulse evokes sufficient GABA re lease, presumably from JG cells, to activate GABA(B) receptors on ON termin als. Thus GABA(B) heteroreceptors on ON terminals are activated by ambient levels of extrasynaptic GABA, and by ON input to the OB. The time course of ON-evoked, GABA(B) presynaptic inhibition suggests that neurotransmission to M/T cells and JG cells will be significantly suppressed when ON impulses arrive in glomeruli at 2.5-20 Hz. GABA(B) receptor-mediated presynaptic in hibition of sensory input to the OB may play an important role in shaping t he activation pattern of the OB glomeruli during olfactory coding.