Aroniadou-Anderjaska V, Zhou F M, Priest C A, Ennis M, Shipley M T
Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Neurophysiol. 2000 Sep;84(3):1194-203. doi: 10.1152/jn.2000.84.3.1194.
Olfactory receptor neurons of the nasal epithelium send their axons, via the 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 juxtaglomerular (JG) interneurons. Many JG cells are GABAergic. Here we show that, despite the absence of conventional synapses, GABA released from JG cells activates 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 recording techniques were used in rat OB slices. Baclofen (2-5 microM), a GABA(B) agonist, completely suppressed ON-evoked synaptic responses of both mitral/tufted cells and JG cells, with no evidence for postsynaptic effects. Baclofen (0.5-1 microM) also reversed paired-pulse depression (PPD) of mitral/tufted cell responses to paired-pulse facilitation (PPF), and reduced depression of JG cell excitatory postsynaptic currents (EPSCs) during repetitive ON stimulation. These results suggest that baclofen reduced the probability 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 tonically suppressed via GABA(B) receptors. The same antagonists reduced PPD of ON-evoked mitral/tufted cell responses at interstimulus intervals 50-400 ms. This finding suggests that a single ON impulse evokes sufficient GABA release, presumably from JG cells, to activate GABA(B) receptors on ON terminals. 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 inhibition of sensory input to the OB may play an important role in shaping the activation pattern of the OB glomeruli during olfactory coding.
鼻上皮的嗅觉受体神经元通过嗅神经（ON）将其轴突发送到嗅球（OB）的肾小球，在那里轴突末端与OB的输出细胞——二尖瓣细胞和簇状细胞的顶端树突以及与近肾小球（JG）中间神经元形成谷氨酸能突触。许多JG细胞是γ-氨基丁酸能的。在这里，我们表明，尽管没有传统的突触，但从JG细胞释放的γ-氨基丁酸激活了ON末端的γ-氨基丁酸B（GABA(B)）受体，并在静息状态下以及对ON刺激的反应中抑制谷氨酸释放。在大鼠OB切片中使用了场电位记录和电流源密度分析，以及细胞内和全细胞记录技术。GABA(B)激动剂巴氯芬（2 - 5微摩尔）完全抑制了二尖瓣/簇状细胞和JG细胞的ON诱发的突触反应，没有证据表明有突触后效应。巴氯芬（0.5 - 1微摩尔）还将二尖瓣/簇状细胞对配对脉冲的反应的配对脉冲抑制（PPD）逆转成双脉冲易化（PPF），并减少了重复ON刺激期间JG细胞兴奋性突触后电流（EPSCs）的抑制。这些结果表明巴氯芬降低了ON末端谷氨酸释放的概率。GABA(B)拮抗剂CGP35348或CGP55845A增加了单脉冲ON刺激诱发的二尖瓣/簇状细胞反应，表明ON末端的谷氨酸释放通过GABA(B)受体被静息抑制。相同的拮抗剂在刺激间隔50 - 400毫秒时降低了ON诱发的二尖瓣/簇状细胞反应的PPD。这一发现表明单个ON冲动诱发了足够的γ-氨基丁酸释放，大概是从JG细胞释放的，以激活ON末端的GABA(B)受体。因此，ON末端的GABA(B)异受体被突触外γ-氨基丁酸的环境水平以及ON对OB的输入激活。ON诱发的GABA(B)突触前抑制的时间进程表明，当ON冲动以2.5 - 20赫兹的频率到达肾小球时，向M/T细胞和JG细胞的神经传递将被显著抑制。GABA(B)受体介导的对OB感觉输入的突触前抑制可能在嗅觉编码过程中塑造OB肾小球的激活模式中起重要作用。
