title: Large projection neurons in lamina I of the rat spinal cord that lack the neurokinin 1 receptor are densely innervated by VGLUT2-containing axons and possess GluR4-containing AMPA receptors.
abstract: Although most projection neurons in lamina I express the neurokinin 1 receptor (NK1r), we have identified a population of large multipolar projection cells that lack the NK1r, are characterized by the high density of gephyrin puncta that coat their cell bodies and dendrites, and express the transcription factor Fos in response to noxious chemical stimulation. Here we show that these cells have a very high density of glutamatergic input from axons with strong immunoreactivity for vesicular glutamate transporter 2 that are likely to originate from excitatory interneurons. However, they receive few contacts from peptidergic primary afferents or transganglionically labeled Adelta nociceptors. Unlike most glutamatergic synapses in superficial laminas, those on the gephyrin-coated cells contain the GluR4 subunit of the AMPA receptor. A noxious heat stimulus caused Fos expression in 38% of the gephyrin-coated cells but in 85% of multipolar NK1r-immunoreactive cells. These findings are consistent with the suggestion that there is a correlation between function and morphology for lamina I neurons but indicate that there are at least two populations of multipolar neurons that differ in receptor expression, excitatory inputs, and responses to noxious stimulation. Although there are only approximately 10 gephyrin-coated cells on each side per segment in the lumbar enlargement, they constitute approximately 18% of the lamina I component of the spinothalamic tract at this level, which suggests that they play an important role in transmission of nociceptive information to the cerebral cortex. Our results also provide the first evidence that postsynaptic GluR4-containing AMPA receptors are involved in spinal nociceptive transmission.
authors.affiliation: Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Erika
authors.initials: E
authors.lastname: Polgár
authors.forename: Khulood M
authors.initials: KM
authors.lastname: Al-Khater
authors.forename: Safa
authors.initials: S
authors.lastname: Shehab
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Todd
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D048430:Cell Shape / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013133:Spinothalamic Tracts / Q000166:cytology / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; D018040:Receptors, Neurokinin-1; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; C073441:gephyrin; C104724:glutamate receptor ionotropic, AMPA 4; D013373:Substance P; D018698:Glutamic Acid