Synaptic amplification by dendritic spines enhances input cooperativity
Open accessAbstract
Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines. However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation. Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (R(neck)) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that R(neck) is large enough (~500 MΩ) to amplify substantially the spine head depolarization associated with a unitary synaptic input by ~1.5- to ~45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an R(neck)-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons.
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Because of the high spine neck resistance (~1 GΩ), an unpotentiated EPSP can approximate 25 mV.
“Because of the high spine neck resistance (∼1 GΩ) it is calculated that an unpotentiated EPSP can approximate 25 mV (185, 186).”
From Synaptic memory and CaMKII (2023) · cites this paper as [185]
The passage labeled Abstract (page not provided) estimates a spine-head depolarization of ~25 mV for an average unitary event, based on a ~0.5 mV dendritic EPSP. But it reports spine-neck resistance of 514 ± 44 MΩ, not ~1 GΩ, and does not specify that the event is unpotentiated. (LLM, conf=0.89)
Experimental — accuracy not yet measuredActive properties of dendritic spines play an important role in interactions between multiple synaptic inputs in dendritic computation.
“These active properties of dendritic spines are thought to play an important role in the interactions between multiple synaptic inputs in dendritic computation (Araya et al., 2007; Harnett et al., 2012).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Harnett et al., 2012
Activating VDCCs, which are present in spines, evokes cytosolic spine Ca2+ transients and the activation of cytosolic spine CaMKII.
“Activating VDCCs, which are present in spines, evokes cytosolic spine Ca2+ transients (185–187) and the activation of cytosolic spine CaMKII (188).”
From Synaptic memory and CaMKII (2023) · cites this paper as [185]
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- Authors
- Harnett, M. T., Makara, J. K., Spruston, N., Kath, W. L., & Magee, J. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Northwestern University (US)
- Corresponding author
- Magee, Jeffrey C.
- Venue
- Nature
- Published
- 2012-10-28
- Volume
- 491
- Issue
- 7425
- Pages
- 599-602
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3504647
- OpenAlex
- W2068904459
- Cited by
- 288
- References
- 40
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 23 · 2023: 20 · 2022: 21 · 2021: 17 · 2020: 18 · 2019: 18 · 2018: 15 · 2017: 28 · 2016: 24 · 2015: 26 · 2014: 25 · 2013: 25 · 2012: 1
- FWCI
- 10.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (090915)
- National Institute of Neurological Disorders and Stroke (R01NS046064, NS-077601, R01NS077601, NS046064)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, dendritic integration, CA1 pyramidal neurons, dendritic compartmentalization, synaptic plasticity
- MeSH terms
- Animals, Male, Models, Neurological, Synapses, Electric Impedance, Rats, Sprague-Dawley, Rats, Wistar, Pyramidal Cells, Excitatory Postsynaptic Potentials, Dendritic Spines, Rats
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