TY - JOUR T1 - Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3016 LP - 3023 DO - 10.1523/JNEUROSCI.2141-15.2016 VL - 36 IS - 10 AU - Jennifer Robinson AU - Frédéric Manseau AU - Guillaume Ducharme AU - Bénédicte Amilhon AU - Erika Vigneault AU - Salah El Mestikawy AU - Sylvain Williams Y1 - 2016/03/09 UR - http://www.jneurosci.org/content/36/10/3016.abstract N2 - The medial septum and diagonal band of Broca (MS-DBB) has an essential role for theta rhythm generation in the hippocampus and is critical for learning and memory. The MS-DBB contains cholinergic, GABAergic, and recently described glutamatergic neurons, but their specific contribution to theta generation is poorly understood. Here, we examined the role of MS-DBB glutamatergic neurons in theta rhythm using optogenetic activation and electrophysiological recordings performed in in vitro preparations and in freely behaving mice. The experiments in slices suggest that MS-DBB glutamatergic neurons provide prominent excitatory inputs to a majority of local GABAergic and a minority of septal cholinergic neurons. In contrast, activation of MS-DBB glutamatergic fiber terminals in hippocampal slices elicited weak postsynaptic responses in hippocampal neurons. In the in vitro septo-hippocampal preparation, activation of MS-DBB glutamatergic neurons did increase the rhythmicity of hippocampal theta oscillations, whereas stimulation of septo-hippocampal glutamatergic fibers in the fornix did not have an effect. In freely behaving mice, activation of these neurons in the MS-DBB strongly synchronized hippocampal theta rhythms over a wide range of frequencies, whereas activation of their projections to the hippocampus through fornix stimulations had no effect on theta rhythms, suggesting that MS-DBB glutamatergic neurons played a role in theta generation through local modulation of septal neurons. Together, these results provide the first evidence that MS-DBB glutamatergic neurons modulate local septal circuits, which in turn contribute to theta rhythms in the hippocampus.SIGNIFICANCE STATEMENT The current paper explores the functional role of septal glutamatergic neurons, a recently identified population, in theta rhythm generation in the hippocampus. Using optogenetics and electrophysiology, we have explored the functional connectivity of these neurons in vitro, as well as their influence on theta rhythms both in vitro and in vivo, and show that this neuronal population can powerfully drive theta rhythms through intraseptal connections. These results strongly suggest a role of glutamatergic neurons in theta rhythm generation and may therefore be important for learning and memory. ER -