title: Modulation of distal calcium electrogenesis by neuropeptide Y₁ receptors inhibits neocortical long-term depression.
abstract: 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.
authors.affiliation: Department of Pharmacology and Centre for Neuroscience, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Hamilton
authors.forename: Sara
authors.initials: S
authors.lastname: Xapelli
authors.forename: Sheldon D
authors.initials: SD
authors.lastname: Michaelson
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Larkum
authors.forename: William F
authors.initials: WF
authors.lastname: Colmers
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D019579:Neocortex / Q000378:metabolism / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D018013:Receptors, Neuropeptide / Q000502:physiology*
chemical_list: C066211:Npy1r protein, rat; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D002118:Calcium