Hippocampal Neural Circuits Respond to Optogenetic Pacing of Theta Frequencies by Generating Accelerated Oscillation Frequencies
Open accessAbstract
Biological oscillations can be controlled by a small population of rhythmic pacemaker cells, or in the brain, they also can emerge from complex cellular and circuit-level interactions. Whether and how these mechanisms are combined to give rise to oscillatory patterns that govern cognitive function are not well understood. For example, the activity of hippocampal networks is temporally coordinated by a 7- to 9-Hz local field potential (LFP) theta rhythm, yet many individual cells decouple from the LFP frequency to oscillate at frequencies ∼1 Hz higher. To better understand the network interactions that produce these complex oscillatory patterns, we asked whether the relative frequency difference between LFP and individual cells is retained when the LFP frequency is perturbed experimentally. We found that rhythmic optogenetic stimulation of medial septal GABAergic neurons controlled the hippocampal LFP frequency outside of the endogenous theta range, even during behavioral states when endogenous mechanisms would otherwise have generated 7- to 9-Hz theta oscillations. While the LFP frequency matched the optogenetically induced stimulation frequency, the oscillation frequency of individual hippocampal cells remained broadly distributed, and in a subset of cells including interneurons, it was accelerated beyond the new base LFP frequency. The inputs from septal GABAergic neurons to the hippocampus, therefore, do not appear to directly control the cellular oscillation frequency but rather engage cellular and circuit mechanisms that accelerate the rhythmicity of individual cells. Thus, theta oscillations are an example of cortical oscillations that combine inputs from a subcortical pacemaker with local computations to generate complex oscillatory patterns that support cognitive functions.
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The frequency of theta oscillations can be experimentally manipulated by optogenetically activating pacemaker cells within the medial septum as well as local FS interneurons within the hippocampus.
“The frequency of theta oscillations can be experimentally manipulated by optogenetically activating pacemaker cells within the medial septum102 as well as local FS interneurons within the hippocampus103.”
From Place and behavioral modulation of hippocampal neurons during immobility (2026) · cites this paper as [102]
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- Authors
- Zutshi, I., Brandon, M. P., Fu, M. L., Donegan, M. L., Leutgeb, J. K., & Leutgeb, S.
- Affiliations
- University of California San Diego (US)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Brandon, Mark P.
- Leutgeb, Stefan
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 28
- Issue
- 8
- Pages
- 1179-1188.e3
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC6488523
- OpenAlex
- W2795830621
- Cited by
- 103
- References
- 51
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 27 · 2023: 9 · 2022: 10 · 2021: 16 · 2020: 9 · 2019: 8 · 2018: 3
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (FMH096531A, R01 MH100349, R21 MH100354, R01 NS, 102915, R01 NS084324)
- Howard Hughes Medical Institute International Student Research Fellowship
- Whitehall Foundation (2012-0685)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampal theta rhythm, local field potentials, optogenetic stimulation, medial septum, GABAergic neurons, interneurons, pacemaker cells, cortical oscillations, neural circuits
- MeSH terms
- Animals, Hippocampus, Interneurons, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Temporal Lobe, Theta Rhythm, Pyramidal Cells, GABAergic Neurons, Optogenetics
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