Modulation of distal calcium electrogenesis by neuropeptide Y₁ receptors inhibits neocortical long-term depression
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In layer 5 neocortical pyramidal neurons, backpropagating action potentials (bAPs) firing at rates above a critical frequency (CF) induce supralinear Ca²⁺ influx and regenerative potentials in apical dendrites. Paired temporally with an EPSP, this Ca²⁺ influx can result in synaptic plasticity. We studied the actions of neuropeptide Y (NPY), an abundant neocortical neuropeptide, on Ca²⁺ influx in layer 5 pyramidal neurons of somatosensory neocortex in Sprague Dawley and Wistar rats, using a combination of somatic and dendritic intracellular recordings and simultaneous Ca²⁺ imaging. Ca²⁺ influx induced by trains of bAPs above a neuron's CF was inhibited by NPY, acting only at the distal dendrite, via Y₁ receptors. NPY does not affect evoked synaptic glutamate release, paired synaptic facilitation, or synaptic rundown in longer trains. Extracellular Cs⁺ did not prevent NPY's postsynaptic effects, suggesting it does not act via either G-protein-activated inwardly rectifying K⁺ conductance (G(IRK)) or hyperpolarization-activated, cyclic nucleotide-gated channels. NPY application suppresses the induction of the long-term depression (LTD) normally caused by pairing 100 EPSPs with bursts of 2 bAPs evoked at a supracritical frequency. These findings suggest that distal dendritic Ca²⁺ influx is necessary for LTD induction, and selective inhibition of this distal dendritic Ca²⁺ influx by NPY can thus regulate synaptic plasticity in layer 5 pyramidal neurons.
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NP-GPCRs could play roles in credit assignment analogous to those postulated for dopamine-selective GPCRs.
“commonalities of signal transduction downstream from widely varying GPCRs suggest that NP-GPCRs could play roles in credit assignment analogous to those postulated for dopamine-selective GPCRs (Hamilton et al., 2013; Roelfsema and Holtmaat, 2018; but see Edelmann and Lessmann, 2011).”
From Single-cell transcriptomic evidence for dense intracortical neuropeptide networks (2019) · cites this paper as Hamilton et al., 2013
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- Authors
- Hamilton, T. J., Xapelli, S., Michaelson, S. D., Larkum, M. E., & Colmers, W. F.
- Affiliations
- University of Alberta (CA)
- University of Coimbra (PT)
- Humboldt-Universität zu Berlin (DE)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-07-03
- Volume
- 33
- Issue
- 27
- Pages
- 11184-11193
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6618610
- OpenAlex
- W2095444187
- Cited by
- 11
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Alberta
- Fondation pour la Recherche Médicale
- Canadian Institutes of Health Research (MT10520, OTG88592)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- neuropeptide Y, Y1 receptor, long-term depression, backpropagating action potentials, layer 5 pyramidal neurons, somatosensory cortex, synaptic plasticity, paired-pulse facilitation, critical frequency, dendritic calcium imaging
- MeSH terms
- Animals, Calcium, Hippocampus, Male, Neural Inhibition, Rats, Sprague-Dawley, Rats, Wistar, Receptors, Neuropeptide, Neocortex, Long-Term Synaptic Depression, Receptors, G-Protein-Coupled, Rats
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