LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance
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Excitatory hilar mossy cells (MCs) in the dentate gyrus receive inputs from dentate granule cells (GCs) and project back to GCs locally, contralaterally, and along the longitudinal axis of the hippocampus, thereby establishing an associative positive-feedback loop and connecting functionally diverse hippocampal areas. MCs also synapse with GABAergic interneurons that mediate feed-forward inhibition onto GCs. Surprisingly, although these circuits have been implicated in both memory formation (e.g., pattern separation) and temporal lobe epilepsy, little is known about activity-dependent plasticity of their synaptic connections. Here, we report that MC-GC synapses undergo a presynaptic, NMDA-receptor-independent form of long-term potentiation (LTP) that requires postsynaptic brain-derived neurotrophic factor (BDNF)/TrkB and presynaptic cyclic AMP (cAMP)/PKA signaling. This LTP is input specific and selectively expressed at MC-GC synapses, but not at the disynaptic inhibitory loop. By increasing the excitation/inhibition balance, MC-GC LTP enhances GC output at the associative MC-GC recurrent circuit and may contribute to dentate-dependent forms of learning and epilepsy.
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PKI 14-22 treatment blocked the forskolin-induced increase in Munc13-1 clusters and decreased their number.
“Application of alternative PKA inhibitor, PKI 14–22 [79] similarly blocked the increase in Munc13-1 clusters, and even decreased their number (S9A–S9D Fig; number of clusters–control: 2.4 ± 1.1 (mean ± SD), median 2, n = 62 AZs, N = 5 mice; PKI: 2.0 ± 1.0, median 2, n = 57 AZs, N = 3 mice; PKI + forskolin: 1.9 ± 1.0, median 2, n = 59 AZs, N = 3 mice; control versus PKI: P = 0.0514, control versus”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [79]
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Activation of Extrasynaptic Kainate Receptors Drives Hilar Mossy Cell Activity
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The Amyloid Precursor Protein Regulates Synaptic Transmission at Medial Perforant Path Synapses
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Pre- versus Post-synaptic Forms of LTP in Two Branches of the Same Hippocampal Afferent
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Self-citationKv4.2 Regulates Basal Synaptic Strength by Inhibiting R-Type Calcium Channels in the Hippocampus
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Neurophotonics Approaches for the Study of Pattern Separation
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Circuit-based intervention corrects excessive dentate gyrus output in the fragile X mouse model
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BDNF induces its own release to mediate presynaptic plasticityPreprint
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XIth Cajal Conference: New frontiers in neuron‐glial plasticity in health and disease
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Circuit-based intervention corrects excessive dentate gyrus output in the fragile X mouse model
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Hippocampal Dentate Mossy Cells Improve Their CV and Trk into the Limelight
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Hippocampus - More than Just Memory
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Neuronal Primary Cilia Mediate Noggin Release to Enable Extracellular Signaling
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- Authors
- Hashimotodani, Y., Nasrallah, K., Jensen, K. R., Chávez, A. E., Carrera, D., & Castillo, P. E.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Castillo, Pablo E.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 95
- Issue
- 4
- Pages
- 928-943.e3
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5609819
- OpenAlex
- W2747342617
- Cited by
- 104
- References
- 77
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 21 · 2023: 17 · 2022: 15 · 2021: 13 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 2
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (DA017392, MH081935)
- Japan Society for the Promotion of Science (H23.829)
- Fondation pour la Recherche Médicale
- Fondation Bettencourt Schueller
- Ruth L. Kirschstein Award (F32 NS071821)
- Brain & Behavior Research Foundation
- Millennium Nucleus Nu-MIND (NC 130011)
- Maximizing Access to Research Careers Program (T34 GM008718)
- Albert Einstein College of Medicine (R25 GM104547)
- 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, dentate gyrus granule cells, excitation-inhibition balance, BDNF/TrkB signaling, cAMP/PKA signaling, presynaptic plasticity, feedforward inhibition, temporal lobe epilepsy, pattern separation
- MeSH terms
- Channelrhodopsins, Animals, Animals, Newborn, Enzyme Inhibitors, Female, Male, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Synapses, Signal Transduction, Rats, Sprague-Dawley, Receptors, Presynaptic, Long-Term Potentiation, Neurotransmitter Agents, Dentate Gyrus, Brain-Derived Neurotrophic Factor, Mossy Fibers, Hippocampal, Receptor, trkB, Long-Term Synaptic Depression, Mice, Rats
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