A role for ERKII in synaptic pattern selectivity on the time‐scale of minutes

Ajay, Sriram M.; Bhalla, Upinder S.

doi:10.1111/j.1460-9568.2004.03725.x

Cited by 64Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeural dynamics and brain function

A role for ERKII in synaptic pattern selectivity on the time‐scale of minutes

Ajay, Sriram M., Bhalla, Upinder S.·2004·European Journal of Neuroscience

DOI 10.1111/j.1460-9568.2004.03725.x

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Abstract

Stimulus reinforcement strengthens learning. Intervals between reinforcement affect both the kind of learning that occurs and the amount of learning. Stimuli spaced by a few minutes result in more effective learning than when massed together. There are several synaptic correlates of repeated stimuli, such as different kinds of plasticity and the amplitude of synaptic change. Here we study the role of signalling pathways in the synapse on this selectivity for spaced stimuli. Using the in vitro hippocampal slice technique we monitored long‐term potentiation (LTP) amplitude in CA1 for repeated 100‐Hz, 1‐s tetani. We observe the highest LTP levels when the inter‐tetanus interval is 5–10 min. We tested biochemical activity in the slice following the same stimuli, and found that extracellular signal‐regulated kinase type II (ERKII) but not CaMKII exhibits a peak at about 10 min. When calcium influx into the slice is buffered using AM‐ester calcium dyes, amplitude of the physiological and biochemical response is reduced, but the timing is not shifted. We have previously used computer simulations of synaptic signalling to predict such temporal tuning from signalling pathways. In the current study we consider feedback and feedforward models that exhibit temporal tuning consistent with our experiments. We find that a model incorporating post‐stimulus build‐up of PKM zeta acting upstream of mitogen‐activated protein kinase is sufficient to explain the observed temporal tuning. On the basis of these combined experimental and modelling results we propose that the dynamics of PKM activation and ERKII signalling may provide a mechanism for functionally important forms of synaptic pattern selectivity.

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In a hippocampal slice preparation, 5-10-minute intervals between tetani were ideal for induction of LTP, and they produced similar levels of LTP, with longer or shorter intervals yielding both less LTP and less ERK1/2 activation.
“One study80 found that in a hippocampal slice preparation, 5–10-minute intervals between tetani were ideal for induction of LTP, and they produced similar levels of LTP, with longer or shorter intervals yielding both less LTP and less ERK1/2 activation.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [80]
Simulations have reproduced the dynamics of MAPK during LTP induction.
“Simulations have reproduced the dynamics of MAPK during LTP induction80,86,88.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [80]

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Authors: Ajay, S. M., & Bhalla, U. S.
Affiliations: Tata Institute of Fundamental Research (IN)
ORCID: Bhalla, Upinder S.
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2004-11
Volume: 20
Issue: 10
Pages: 2671-2680
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/j.1460-9568.2004.03725.x
OpenAlex: W1972107254
Cited by: 64
References: 61
Citations by year: 2026: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 7 · 2014: 4 · 2013: 8 · 2012: 3
FWCI: 0.94
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 10 d)
Locations: European Journal of Neuroscience (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: long-term potentiation, CA1, mitogen-activated protein kinase, CaMKII, calcium influx, synaptic plasticity, temporal tuning, hippocampus
MeSH terms: Animals, Animals, Newborn, Calcium, Computer Simulation, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Electric Stimulation, Fluoresceins, Hippocampus, Male, Models, Neurological, Synaptic Transmission, Neurons, Synapses, Time Factors, Blotting, Western, Excitatory Postsynaptic Potentials, Mitogen-Activated Protein Kinase 1, Calcium Signaling, Vesicular Transport Proteins, SNARE Proteins, Rats, In Vitro Techniques

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A role for ERKII in synaptic pattern selectivity on the time‐scale of minutes

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