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J Neurosci. 2016 Mar 9;36(10):3016-23. doi: 10.1523/JNEUROSCI.2141-15.2016.

Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms.

Author information

1
Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
2
Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada sylvain.williams@gmail.com.

Abstract

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.

KEYWORDS:

glutamatergic; hippocampus; septum; theta

PMID:
26961955
DOI:
10.1523/JNEUROSCI.2141-15.2016
[Indexed for MEDLINE]
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