Duchamp-Viret P, Duchamp A
Laboratoire de Physiologie Neurosensorielle, Université Claude Bernard, Villeurbanne, France.
Neuroscience. 1993 Oct;56(4):905-14. doi: 10.1016/0306-4522(93)90136-4.
In the olfactory bulb, the activity of the output neurons, the mitral cells, is under inhibitory control exerted by GABAergic interneurons, the granule cells. Although the mechanisms of this inhibition are well known from in vitro studies, its physiological role in controlling mitral cell activity in response to odours has never been investigated. This study planned to improve understanding of the involvement of granule cells. To do so, GABAA-synaptic mechanisms were altered using GABAA antagonists in order to observe the consequences on mitral cell electrophysiological responses to odours, delivered over a wide concentration range. Due to the laminar organization of bulbar cell populations, the antagonists picrotoxin or bicuculline were injected into the bulbar ventricle in order to block granule cell inhibitory action at first. Surprisingly, the early consequence of the antagonist injection was a decrease in cell responsivity: response spike frequencies were lowered while thresholds were occasionally shifted toward higher concentrations. This initial depressive effect was followed by a recovery of control excitability and, later, by an increase in excitability: spike bursts became more sustained in frequency and in duration. At the same time, in most of the cells studied, spontaneous activity became bursting. The early depressive effect of GABAA antagonists is discussed in terms of an enhancement of the inhibitory influence of granule cells on mitral cells. This might reflect a blocking action of the antagonists at the level of GABAergic synapses located on granule cells themselves. The late effect, an increase in excitability, is explained as the consequence of the alteration of the functioning of dendrodendritic synapses between granule and mitral cells leading to a disinhibition of the latter. The comparison of the present findings with others obtained when antagonists were applied on to glomerular layers led us to infer that granule cell inhibition would be devoted to limiting mitral cell responses in frequency and in duration rather than to adjusting their response threshold. The chronology of the effects observed strongly supports the fact that, following the intraventricular injection, the antagonists acted primarily in the deep layers of the bulb. Nevertheless, due to free diffusion starting from the injection site, the possibility that drugs act later in the glomerular layer can not be rejected. It can be concluded that, in addition to its extensive involvement through intrinsic interneurons, GABA might also control the strength of the inhibition exerted by granule cells on mitral cells via centrifugal fibres.
在嗅球中，输出神经元即僧帽细胞的活动受到GABA能中间神经元（颗粒细胞）施加的抑制性控制。尽管这种抑制的机制在体外研究中已为人熟知，但其在控制僧帽细胞对气味反应中的生理作用从未被研究过。本研究旨在增进对颗粒细胞所起作用的理解。为此，使用GABAA拮抗剂改变GABAA突触机制，以观察对僧帽细胞对气味的电生理反应的影响，气味浓度范围广泛。由于嗅球细胞群体的分层组织，将拮抗剂印防己毒素或荷包牡丹碱注入嗅球脑室，以便首先阻断颗粒细胞的抑制作用。令人惊讶的是，注射拮抗剂的早期后果是细胞反应性降低：反应峰频率降低，而阈值偶尔会向更高浓度偏移。这种最初的抑制作用之后是对照兴奋性的恢复，随后是兴奋性增加：峰发放的频率和持续时间变得更持久。与此同时，在大多数研究的细胞中，自发活动变得成簇。GABAA拮抗剂的早期抑制作用从颗粒细胞对僧帽细胞抑制影响的增强方面进行了讨论。这可能反映了拮抗剂在颗粒细胞自身上的GABA能突触水平的阻断作用。后期效应，即兴奋性增加，被解释为颗粒细胞和僧帽细胞之间树突 - 树突突触功能改变导致后者去抑制的结果。将本研究结果与在肾小球层应用拮抗剂时获得的其他结果进行比较，使我们推断颗粒细胞抑制将致力于限制僧帽细胞反应的频率和持续时间，而不是调整其反应阈值。所观察到的效应的时间顺序有力地支持了这样一个事实，即脑室注射后，拮抗剂主要在嗅球深层起作用。然而，由于从注射部位开始的自由扩散，不能排除药物稍后在肾小球层起作用的可能性。可以得出结论，除了通过内在中间神经元广泛参与外，GABA还可能通过离心纤维控制颗粒细胞对僧帽细胞施加的抑制强度。
