Theta-burst LTP
Open accessAbstract
This review covers the spatial and temporal rules governing induction of hippocampal long-term potentiation (LTP) by theta-burst stimulation. Induction of LTP in field CA1 by high frequency stimulation bursts that resemble the burst discharges (complex-spikes) of hippocampal pyramidal neurons involves a multiple-step mechanism. A single burst is insufficient for LTP induction because it evokes both excitatory and inhibitory currents that partially cancel and limit postsynaptic depolarization. Bursts repeated at the frequency (~5 Hz) of the endogenous theta rhythm induce maximal LTP, primarily because this frequency disables feed-forward inhibition and allows sufficient postsynaptic depolarization to activate voltage-sensitive NMDA receptors. The disinhibitory process, referred to as "priming", involves presynaptic GABA autoreceptors that inhibit GABA release. Activation of NMDA receptors allows a calcium flux into dendritic spines that serves as the proximal trigger for LTP. We include new data showing that theta-burst stimulation is more efficient than other forms of stimulation for LTP induction. In addition, we demonstrate that associative interactions between synapses activated during theta-bursts are limited to major dendritic domains since such interactions occur within apical or basal dendritic trees but not between them. We review evidence that recordings of electrophysiological responses during theta burst stimulation can help to determine if experimental manipulations that affect LTP do so by affecting events antecedent to the induction process, such as NMDA receptor activation, or downstream signaling cascades that result from postsynaptic calcium fluxes. Finally, we argue that theta-burst LTP represents a minimal model for stable, non-decremental LTP that is more sensitive to a variety of experimental manipulations than is LTP induced by other stimulation paradigms. This article is part of a Special Issue entitled SI: Brain and Memory.
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In iTBS, 50 Hz triplets are applied at a theta rhythm of 5 Hz, which is thought to facilitate long-term potentiation in less time and with fewer pulses than standard TMS, which generally is administered at 5 to 10 Hz.
“In iTBS, 50 Hz triplets are applied at a theta rhythm (5 Hz), which is thought to facilitate long-term potentiation in less time and with fewer pulses than standard TMS, which generally is administered at 5 to 10 Hz [57].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [57]
The Introduction (page unavailable) describes theta bursts repeated at 5 Hz for LTP induction, and ‘Economy’ of Theta-Burst Stimulation (page unavailable) reports that theta bursts induced LTP with fewer pulses than unpatterned stimulation. The experiments described used four-pulse bursts at 100 Hz in hippocampal tissue; these passages do not establish the 50 Hz triplets of iTBS, a shorter administration time, or a comparison with standard TMS administered at 5–10 Hz. (LLM, conf=0.88)
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- Authors
- Larson, J., & Munkácsy, E.
- Affiliations
- University of Illinois Chicago (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Larson, John
- ORCID
- Munkácsy, Erin
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 1621
- Pages
- 38-50
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4411212
- OpenAlex
- W1974528572
- Cited by
- 285
- References
- 110
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 37 · 2023: 26 · 2022: 38 · 2021: 41 · 2020: 23 · 2019: 23 · 2018: 23 · 2017: 11 · 2016: 12 · 2015: 4
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Brain Research (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (DC005793, T32 AG021890)
- Department of Defense (USAMRMC 10917352)
- UIC Honors College, UIC College of Liberal Arts and Sciences
- Glenn Foundation for Medical Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- theta burst stimulation, long-term potentiation, hippocampus, CA1, feedforward inhibition, disinhibition, NMDA receptor, dendritic calcium signaling, dendritic domains, synaptic plasticity
- MeSH terms
- Animals, Electric Stimulation, Hippocampus, Humans, Membrane Potentials, Synapses, Long-Term Potentiation, Pyramidal Cells
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