Bassant Marie-Hélène, Simon Axelle, Poindessous-Jazat Frédérique, Csaba Zsolt, Epelbaum Jacques, Dournaud Pascal
Institut National de la Santé et de la Recherche Médicale, U549, Centre Paul Broca, F-75014 Paris, France.
J Neurosci. 2005 Feb 23;25(8):2032-41. doi: 10.1523/JNEUROSCI.4619-04.2005.
GABAergic septohippocampal neurons play a major role in the generation of hippocampal theta rhythm, but modulatory factors intervening in this function are poorly documented. The neuropeptide somatostatin (SST) may be one of these factors, because nearly all hippocampal GABAergic neurons projecting to the medial septum/diagonal band of Broca (MS-DB) express SST. In this study, we took advantage of the high and selective expression of the SST receptor sst2A in MS-DB to examine its possible role on theta-related activity. Immunohistochemical experiments demonstrated that sst2A receptors were selectively targeted to the somatodendritic domain of neurons expressing the GABAergic marker GAD67 but were not expressed by cholinergic neurons. In addition, a subpopulation of GABAergic septohippocampal projecting neurons expressing parvalbumin (PV) also displayed sst2A receptors. Using in vivo juxtacellular recording and labeling with neurobiotin, we showed that a number of bursting and nonbursting neurons exhibiting high discharge rates and brief spikes were immunoreactive for PV or GAD67 and expressed the sst2A receptor. Microiontophoresis applications of SST and the sst2A agonist octreotide (OCT) showed that sst2A receptor activation decreased the discharge rate of both nonbursting and bursting MS-DB neurons and lessened the rhythmic activity of the latter. Finally, intraseptal injections of OCT and SST in freely moving rats reduced the power of hippocampal EEG in the theta band. Together, these in vivo experiments suggest that SST action on MS-DB GABAergic neurons, through sst2A receptors, represents an important modulatory mechanism in the control of theta activity.
γ-氨基丁酸能的隔区-海马神经元在海马θ节律的产生中起主要作用，但关于干预该功能的调节因子的文献记载较少。神经肽生长抑素（SST）可能是其中一个调节因子，因为几乎所有投射到内侧隔核/布罗卡斜角带（MS-DB）的海马γ-氨基丁酸能神经元都表达SST。在本研究中，我们利用SST受体sst2A在MS-DB中的高选择性表达来研究其对θ相关活动的可能作用。免疫组织化学实验表明，sst2A受体选择性地定位于表达γ-氨基丁酸能标记物GAD67的神经元的胞体树突区域，但胆碱能神经元不表达。此外，一群表达小白蛋白（PV）的γ-氨基丁酸能隔区-海马投射神经元也显示有sst2A受体。通过体内细胞旁记录并用神经生物素标记，我们发现许多放电频率高且动作电位短暂的爆发性和非爆发性神经元对PV或GAD67呈免疫反应并表达sst2A受体。微离子透入法施加SST和sst2A激动剂奥曲肽（OCT）表明，sst2A受体激活降低了非爆发性和爆发性MS-DB神经元的放电频率，并减弱了后者的节律性活动。最后，在自由活动的大鼠中向隔核内注射OCT和SST降低了海马脑电图θ频段的功率。总之，这些体内实验表明，SST通过sst2A受体作用于MS-DB的γ-氨基丁酸能神经元，是控制θ活动的一种重要调节机制。
