Elfn1 Regulates Target-Specific Release Probability at CA1-Interneuron Synapses
Open accessAbstract
Although synaptic transmission may be unidirectional, the establishment of synaptic connections with specific properties can involve bidirectional signaling. Pyramidal neurons in the hippocampus form functionally distinct synapses onto two types of interneurons. Excitatory synapses onto oriens-lacunosum moleculare (O-LM) interneurons are facilitating and have a low release probability, whereas synapses onto parvalbumin interneurons are depressing and have a high release probability. Here, we show that the extracellular leucine-rich repeat fibronectin containing 1 (Elfn1) protein is selectively expressed by O-LM interneurons and regulates presynaptic release probability to direct the formation of highly facilitating pyramidal-O-LM synapses. Thus, postsynaptic expression of Elfn1 in O-LM interneurons regulates presynaptic release probability, which confers target-specific synaptic properties to pyramidal cell axons.
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In hippocampus, the facilitating excitatory inputs onto Sst interneurons result from expression of Elfn1 protein, which regulates presynaptic release probability.
“Experiments in the hippocampus have shown that this unusual behavior is the result of the expression on Sst INs of the extracellular leucine-rich repeat fibronectin containing 1 (Elfn1) protein which regulates the release probability of the presynaptic terminal”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Sylwestrak and Ghosh, 2012
The Results report that knocking down Elfn1 reduces facilitation at hippocampal pyramidal-to-O-LM synapses, and the Discussion says postsynaptic Elfn1 regulates their presynaptic release probability. O-LM cells are a subset of Sst interneurons; the paper does not establish that Elfn1 accounts for facilitating inputs onto hippocampal Sst interneurons generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSomatodendritic labeling for Elfn1 is suggested to be specific for O-LMs.
“Similarly, somatodendritic labeling for the extracellular leucine-rich repeat fibronectin containing 1 protein (Elfn1) is suggested to be specific for O-LMs (561, 1073).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1073]
Loss of Elfn1 normalizes transmission across the train of stimuli, with only weak facilitation remaining, suggesting that other factors must be involved in establishing the high Pr of pyramidal neuron-basket cell synapses.
“Rather, loss of Elfn1 normalizes transmission across the train of stimuli, with only weak facilitation remaining (1073), suggesting that other factors must be involved in establishing the high Pr of pyramidal neuron-basket cell synapses.”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1073]
Viral vector-mediated Elfn1 knock down or knockout of Elfn1 reduces the magnitude of short-term facilitation, confirming a role for Elfn1 in establishing a low Pr.
“Viral vector-mediated Elfn1 knock down (1073), or knockout of Elfn1 (1106) reduces the magnitude of short-term facilitation, confirming a role for Elfn1 in establishing a low Pr.”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1073]
Elfn1 is expressed at pyramidal cell synapses onto SST-containing cells but not PV-containing interneurons in both the CA1 and dentate gyrus.
“Elfn1 is expressed at pyramidal cell synapses onto SST-containing cells but not PV-containing interneurons in both the CA1 and dentate gyrus (1073, 1106).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1073]
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References 34 · Cited by 151
- Authors
- Sylwestrak, E. L., & Ghosh, A.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- Corresponding author
- Ghosh, Anirvan
- ORCID
- Sylwestrak, Emily L.
- Venue
- Science
- Published
- 2012-10-26
- Volume
- 338
- Issue
- 6106
- Pages
- 536-540
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5297939
- OpenAlex
- W2117074250
- Cited by
- 151
- References
- 34
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 12 · 2023: 10 · 2022: 11 · 2021: 16 · 2020: 9 · 2019: 12 · 2018: 20 · 2017: 8 · 2016: 6 · 2015: 10 · 2014: 15 · 2013: 5 · 2012: 2
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS067216)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ELFN1, release probability, presynaptic modulation, hippocampal CA1, pyramidal neurons, oriens-lacunosum moleculare interneurons, parvalbumin interneurons, inhibitory synapses, synaptogenesis
- MeSH terms
- Animals, Axons, Cells, Cultured, Humans, Interneurons, Nerve Tissue Proteins, Synaptic Transmission, Synapses, Rats, Inbred LEC, RNA, Small Interfering, Green Fluorescent Proteins, Mice, Rats, Gene Knockdown Techniques, CA1 Region, Hippocampal, HEK293 Cells
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