RT Journal Article
SR Electronic
T1 Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3016
OP 3023
DO 10.1523/JNEUROSCI.2141-15.2016
VO 36
IS 10
A1 Jennifer Robinson
A1 Frédéric Manseau
A1 Guillaume Ducharme
A1 Bénédicte Amilhon
A1 Erika Vigneault
A1 Salah El Mestikawy
A1 Sylvain Williams
YR 2016
UL http://www.jneurosci.org/content/36/10/3016.abstract
AB 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.