Glutamatergic Neurons of the Mouse Medial Septum and Diagonal Band of Broca Synaptically Drive Hippocampal Pyramidal Cells: Relevance for Hippocampal Theta Rhythm

Glutamatergic Neurons of the Mouse Medial Septum and Diagonal Band of Broca Synaptically Drive Hippocampal Pyramidal Cells: Relevance for Hippocampal Theta Rhythm
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DOI:
10.1523/jneurosci.3663-10.2010
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发表时间:
2010-11-24
影响因子:
5.3
通讯作者:
Williams, Sylvain
Williams, Sylvain
中科院分区:
医学1区
文献类型:
--
作者:
Huh, Carey Y. L.;Goutagny, Romain;Williams, Sylvain

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内侧隔和Broca斜角带神经元(MS-DBB)为海马提供重要的输入,并与学习和记忆密切相关。虽然已知胆碱能和GABA能MS-DBB神经元调节海马活动,但最近描述的海马能MS-DBB神经元的作用尚不清楚。在这里,我们研究了电生理特性的mammatergic MS-DBB神经元,并测试它们是否提供了一个功能性的突触输入海马。为了使谷氨酸能神经元可视化,我们使用转基因小鼠的MS-DBB切片,其中绿色荧光蛋白由囊泡谷氨酸转运蛋白2阳性神经元特异性表达,并使用全细胞膜片钳技术表征其特性。为了评估的突触投射的功能,我们使用了在体外隔海马制备,电刺激穹窿或化学激活的MS-DBB使用NMDA微量输注和记录突触后反应在CA 3锥体细胞。我们发现,作为一个群体,mammatergic MS-DBB神经元显示出一组高度异质性的放电模式,包括快速,集群,爆发,和缓慢的放电。值得注意的是,一个显着的比例表现出快速放电特性,突出的Ih,和有节奏的自发放电θ频率类似的GABA能MS-DBB神经元中发现的。MS-DBB的激活导致CA 3锥体细胞中快速的AMPA受体介导的多巴胺能反应。这些结果描述了第一次的电生理签名的mammatergic MS-DBB神经元,他们的节奏性放电特性,以及他们的能力,以驱动海马主要神经元。我们的研究结果表明,海马隔-海马通路可能在海马θ振荡和相关的认知功能中发挥重要作用。
Neurons of the medial septum and diagonal band of Broca (MS-DBB) provide an important input to the hippocampus and are critically involved in learning and memory. Although cholinergic and GABAergic MS-DBB neurons are known to modulate hippocampal activity, the role of recently described glutamatergic MS-DBB neurons is unknown. Here, we examined the electrophysiological properties of glutamatergic MS-DBB neurons and tested whether they provide a functional synaptic input to the hippocampus. To visualize the glutamatergic neurons, we used MS-DBB slices from transgenic mice in which the green fluorescent protein is expressed specifically by vesicular glutamate transporter 2-positive neurons and characterized their properties using whole-cell patch-clamp technique. For assessing the function of the glutamatergic projection, we used an in vitro septohippocampal preparation, electrically stimulated the fornix or chemically activated the MS-DBB using NMDA microinfusions and recorded postsynaptic responses in CA3 pyramidal cells. We found that glutamatergic MS-DBB neurons as a population display a highly heterogeneous set of firing patterns including fast-, cluster-, burst-, and slow-firing. Remarkably, a significant proportion exhibited fast-firing properties, prominent Ih, and rhythmic spontaneous firing at theta frequencies similar to those found in GABAergic MS-DBB neurons. Activation of the MS-DBB led to fast, AMPA receptor-mediated glutamatergic responses in CA3 pyramidal cells. These results describe for the first time the electrophysiological signatures of glutamatergic MS-DBB neurons, their rhythmic firing properties, and their capacity to drive hippocampal principal neurons. Our findings suggest that the glutamatergic septohippocampal pathway may play an important role in hippocampal theta oscillations and relevant cognitive functions.