Roberts C B, Hemond P, Suter K J
Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Neuroscience. 2008 Jul 17;154(4):1337-51. doi: 10.1016/j.neuroscience.2008.04.067. Epub 2008 May 9.
The impact of the A-type GABA (GABA-A) receptor in gonadotropin releasing hormone (GnRH) neurons is controversial. In adult GnRH neurons, the GABA-A receptor conductance has been reported to either hyperpolarize or depolarize GnRH neurons. Regardless of whether GABA is inhibitory or excitatory in GnRH neurons, GABAergic input would be integrated with post-synaptic potentials generated by other synaptic inputs. We used dynamic current clamping and compartmental computer modeling to examine the integration of AMPA-type glutamatergic input and GABA-mediated input in both the hyperpolarizing (inhibitory) and depolarizing (excitatory) modes in GnRH neurons from transgenic mice (Mus Musculus) generated on a C57BL6 background. In both living and model neurons, action potentials were most likely a few ms after a maximum in AMPA conductance coincided with a minimum in inhibitory GABA. Excitatory GABA interacted differently with AMPA, with spikes most likely, in both dynamic clamping of living neurons and in model neurons, when a maximum in AMPA coincided with the decay from peak of a maximum in GABA. Distributing synapses along the dendrite maximized the temporal relationship between AMPA and GABA conductances and therefore, the potential for spiking. Thus, these two dominant neurotransmitters could interact in multiple frames to generate action potentials in GnRH neurons.
A型γ-氨基丁酸(GABA-A)受体在促性腺激素释放激素(GnRH)神经元中的作用存在争议。在成年GnRH神经元中,据报道GABA-A受体电导可使GnRH神经元超极化或去极化。无论GABA在GnRH神经元中是抑制性还是兴奋性的,GABA能输入都会与其他突触输入产生的突触后电位整合。我们使用动态电流钳制和房室计算机建模,研究了在C57BL6背景下产生的转基因小鼠(小家鼠)的GnRH神经元中,AMPA型谷氨酸能输入和GABA介导的输入在超极化(抑制性)和去极化(兴奋性)模式下的整合情况。在活体神经元和模型神经元中,当AMPA电导达到最大值且抑制性GABA达到最小值后几毫秒,最有可能产生动作电位。兴奋性GABA与AMPA的相互作用方式不同,在活体神经元的动态钳制和模型神经元中,当AMPA达到最大值且与GABA最大值的峰值衰减同时出现时,最有可能产生尖峰。沿着树突分布突触可使AMPA和GABA电导之间的时间关系最大化,从而增加产生尖峰的可能性。因此,这两种主要神经递质可以在多个时间框架内相互作用,在GnRH神经元中产生动作电位。