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The Journal of Neuroscience, February 23, 2005, 25(8):2032-2041; doi:10.1523/JNEUROSCI.4619-04.2005

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Behavioral/Systems/Cognitive
Medial Septal GABAergic Neurons Express the Somatostatin sst_2A Receptor: Functional Consequences on Unit Firing and Hippocampal Theta

Marie-Hélène Bassant, Axelle Simon, Frédérique Poindessous-Jazat, Zsolt Csaba, Jacques Epelbaum, and Pascal Dournaud

Institut National de la Santé et de la Recherche Médicale, U549, Centre Paul Broca, F-75014 Paris, France

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 sst_2A in MS-DB to examine its possible role on theta-related activity. Immunohistochemical experiments demonstrated that sst_2A 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 sst_2A 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 sst_2A receptor. Microiontophoresis applications of SST and the sst_2A agonist octreotide (OCT) showed that sst_2A 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 sst_2A receptors, represents an important modulatory mechanism in the control of theta activity.

Key words: neuromodulation; neuropeptide; GABAergic; theta rhythm; medial septum; somatostatin

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Received Oct 13, 2004; revised January 11, 2005; accepted January 12, 2005.

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