Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events

Larson, John; Lynch, Gary

doi:10.1126/science.3704635

Cited by 597Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeural dynamics and brain function

Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events

Larson, John, Lynch, Gary·1986·Science

DOI 10.1126/science.3704635

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Abstract

Electrical stimulation of axons in the hippocampus with short high-frequency bursts that resemble in vivo activity patterns produces stable potentiation of postsynaptic responses when the bursts occur at intervals of 200 milliseconds but not 2 seconds. When a burst was applied to one input and a second burst applied to a different input to the same target neuron 200 milliseconds later, only the synapses activated by the second burst showed stable potentiation. This effect was observed even when the two inputs innervated completely different regions of the postsynaptic cells; but did not occur when the inputs were stimulated simultaneously or when the second burst was delayed by 2 seconds. Intracellular recordings indicated that the first burst extended the decay phase of excitatory postsynaptic potentials evoked 200 milliseconds later. These results suggest that a single burst of axonal stimulation produces a transient, spatially diffuse "priming" effect that prolongs responses to subsequent bursts, and that these altered responses trigger spatially restricted synaptic modifications. The similarity of the temporal parameters of the priming effect and the theta rhythm that dominates the hippocampal electroencephalogram (EEG) during learning episodes suggests that this priming may be involved in behaviorally induced synaptic plasticity.

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The TBS stimulation paradigm mimics endogenous patterns of neural firing associated with induction of LTP and may modulate networks involved in the pathophysiology of depression.
“This stimulation paradigm mimics endogenous patterns of neural firing associated with induction of LTP (Larson and Lynch, 1986;Suppa et al., 2016) and may modulate networks involved in the pathophysiology of depression (Li et al., 2018).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Larson and Lynch, 1986

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Eckles-Smith, K., Clayton, D. A., Bickford, P. C., & Browning, M. D. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00088-7 · Cited by 194 · see citing works
Factors regulating the magnitude of long-term potentiation induced by theta pattern stimulation
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Self-citation
A Model of Atropine‐Resistant Theta Oscillations in Rat Hippocampal Area CA1
Gillies, M. J., Traub, R. D., LeBeau, F. E. N., Davies, C. H., Gloveli, T., Buhl, E., & Whittington, M. A. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.024588 · Cited by 201 · see citing works
“…frequencies (4–12 Hz) are readily observed in the hippocampal formation in vivo and have been implicated in various cognitive processes including processing of visuospatial information (O’Keefe & Nadel, 1978) and in models of memory formation and retrieval (Larson & Lynch, 1986; Buzsáki, 1989).”
Background
Sculpting the hippocampus from within: stress, spines, and CRH
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“During minutes-long stress, CRH release potentiates synaptic plasticity [55,56] and primes long-term potentiation (LTP) [57,58], a cellular process generally believed to underlie learning and memory [59,60].”
Background
Dendritic spikes induce single-burst long-term potentiation
Remy, S., & Spruston, N. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707919104 · Cited by 179 · see citing works
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Slow and fast inhibition and an H-current interact to create a theta rhythm in a model of CA1 interneuron network
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Endogenous Serine Protease Inhibitor Modulates Epileptic Activity and Hippocampal Long-Term Potentiation
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“After stable baseline recording of fEPSPs for 20 min, LTP was induced by a TBS paradigm (Larson and Lynch, 1986).”
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“The theta rhythm has been shown to contribute to synaptic-plasticity processes (Larson and Lynch, 1986; Larson et al., 1986; Greenstein et al., 1988; Alonso et al., 1990; Huerta and Lisman, 1996; Hölscher et al., 1997), and it is thus believed to play a major role in temporal lobe learning and…”
Background
Latent synaptic pathways revealed after tetanic stimulation in the hippocampus
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Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor.
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“Synaptic potentiation was induced with theta-burst stimulation (TBS) (i.e., 10 bursts of 100-Hz stimulation with interburst intervals of 200 ms) (Kramar and Lynch 2003; Larson et al. 1986; Rex et al. 2005).”
BackgroundMethodSelf-citation
Factors regulating the reversibility of long-term potentiation
Staubli, U., & Chun, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00853.1996 · Cited by 169 · see citing works
“Such heterosynaptic depression, however, is not a necessary concomitant of LTP and, in fact, is elicited best hy trains that do not produce LTP, whereas stimulation with the optimal parameters for LTP does not alter the synaptic strength of neighboring, nonstimulated connections (Dunwiddie and Lynch, 1978; Larson and…”
Background
Theta burst stimulation of the prefrontal cortex: Safety and impact on cognition, mood, and resting electroencephalogram
Grossheinrich, N., Rau, A., Pogarell, O., Hennig-Fast, K., Reinl, M., Karch, S., Dieler, A., Leicht, G., Mulert, C., Sterr, A., et al. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.029 · Cited by 168 · see citing works
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Self-citation
Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress
Kumar, A. (2011) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2011.00007 · Cited by 169 · see citing works
“This frequency led investigators to develop theta burst stimulation (TBS) and primedburst stimulation (PBS) protocols (Larson and Lynch, 1986; Rose and Dunwiddie, 1986).”
Background
Reduced K+ Channel Inactivation, Spike Broadening, and After-Hyperpolarization in Kvβ1.1-Deficient Mice with Impaired LearningPreprint
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“Such effects involve longterm potentiation (LTP) and depression (LTD) of synaptic connections (Larson and Lynch, 1986; Huemmeke et al., 2002).”
Background
Donald O. Hebb's synapse and learning rule: a history and commentary
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“They have been suggested to set the temporal dynamics needed to organize synaptic plasticity and implement learning at the network level (Larson and Lynch, 1986; Huerta and Lisman, 1993; Hasselmo et al., 2002).”
Background
Long-lasting potentiation of synaptic potentials in the motor cortex produced by stimulation of the sensory cortex in the cat: a basis of motor learning
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Reversal of LTP by theta frequency stimulation
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Self-citation
Chapter 17 Chapter The nature and causes of hippocampal long-term potentiation
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Self-citation
Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning
Wessel, M. J., Beanato, E., Popa, T., Windel, F., Vassiliadis, P., Menoud, P., Beliaeva, V., Violante, I. R., Abderrahmane, H., Dzialecka, P., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01457-7 · Cited by 173 · see citing works
“23).”
Method

Authors: Larson, J., & Lynch, G.
Affiliations: University of California, Irvine (US)
ORCID: Lynch, Gary
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1986-05-23
Volume: 232
Issue: 4753
Pages: 985-988
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.3704635
OpenAlex: W2077624336
Cited by: 597
References: 0
Citations by year: 2026: 7 · 2025: 6 · 2024: 11 · 2023: 26 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 8 · 2016: 12 · 2015: 8 · 2014: 9 · 2013: 21 · 2012: 12
FWCI: 7.56
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
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: synaptic potentiation, hippocampus, postsynaptic potentials, theta oscillations, synaptic plasticity, learning
MeSH terms: Animals, Electric Stimulation, Hippocampus, Learning, Membrane Potentials, Neuronal Plasticity, Periodicity, Synapses, Rats, In Vitro Techniques

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Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events

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