Developmental regulation and cell-specific expression of N-methyl-D-aspartate receptor splice variants in rat hippocampus

M. C. Paupard, L. K. Friedman, R. Suzanne Zukin

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The present study demonstrates cell-specific and developmental regulation of 5' and 3' splicing of the N-methyl-D-aspartate receptor NR1 subunit within specific neuronal populations of the hippocampus. At birth, NR1 transcripts lacking exon 5 (encoding the amino-terminal splice cassette N1) exhibit mature patterns of labelling within the hippocampus, with high levels of expression in the CA1, CA3, and dentate gyrus. In contrast, exon 5-containing (NR1(1XX)) transcripts are expressed at low levels until P8, at which time expression is prominent and essentially uniform in the CA1, CA3, and dentate gyrus. Exon 5 expression increases at a faster rate in CA3 than in CA1. or dentate gyrus. By the third week postnatal (postnatal day P21), exon 5-containing transcripts exhibit a distinct gradient of labelling, with more intense expression in CA3, than in CA1 or dentate gyrus. By P21 pyramidal neurons of the CA1 and granule cells of the dentate gyrus express mainly NR12(0xx) receptor messenger RNAs (lacking exon 5). Because splicing in of the N1 splice cassette confers greater current amplitude and enhanced potentiation by protein kinase C, these observations predict elevated levels of synaptic activity in the CA1 early in postnatal life, a time at which synaptic plasticity is enhanced. The carboxy-terminal splice cassettes C1 and C2 are regulated independently within the hippocampus. Whereas NR(X11) (C1-C2-containing) and NR1(X01) (C2 only) receptors exhibit high levels of expression in CA1, CA3, and dentate gyrus, NR1(X01) receptors are expressed more intensely in pyramidal neurons of CA3. NR1(X10) receptor expression is very low in all cells and at all times examined, even in adults. Because splicing in of the C1 cassette is thought to regulate receptor targeting, clustering, and cytoskeletal interactions, N-methyl-D-aspartate receptors in the two hippocampal subfields may play differing roles in synaptogenesis and the formation of new neuronal contacts. Moreover, cell-specific patterns of NR(x00) receptor messenger RNAs parallel those of NR1(0XX) receptor messenger RNAs; and cell-specific patterns of NR1(1XX) (N1-containing) receptor messenger RNAs parallels those of NR1(X00) (C1-, C2-lacking) receptor messenger RNAs throughout development. These observations suggest that NR1(X00) receptors, which exhibits the greatest potentiation by protein kinase C, are likely to be important in CA1 during the second and third weeks postnatal. Cell-specific expression of NR1 splice variants undoubtedly contributes to functional diversity of N-methyl-D-aspartate receptor properties in neuronal populations within the hippocampus. Developmental regulation of NR1 splicing is likely to influence synaptic plasticity and the formation of new synaptic contacts. Moreover, findings from this study suggest that a change in NR1 splicing following a neurological injury could significantly alter glutamate pathogenicity in a particular population of cells.

Original languageEnglish (US)
Pages (from-to)399-409
Number of pages11
JournalNeuroscience
Volume79
Issue number2
DOIs
StatePublished - May 12 1997

Fingerprint

N-Methyl-D-Aspartate Receptors
Dentate Gyrus
Hippocampus
Exons
Messenger RNA
Neuronal Plasticity
Pyramidal Cells
Protein Kinase C
Population
Cluster Analysis
Virulence
Glutamic Acid
Parturition
Wounds and Injuries

Keywords

  • Development regulation
  • Excitatory amino acid receptor
  • In situ hybridization
  • Neuroanatomy
  • NMDA receptor splice variant
  • RNA splicing

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Developmental regulation and cell-specific expression of N-methyl-D-aspartate receptor splice variants in rat hippocampus. / Paupard, M. C.; Friedman, L. K.; Zukin, R. Suzanne.

In: Neuroscience, Vol. 79, No. 2, 12.05.1997, p. 399-409.

Research output: Contribution to journalArticle

@article{fe456314637c4c3fb411ea937c1c71b2,
title = "Developmental regulation and cell-specific expression of N-methyl-D-aspartate receptor splice variants in rat hippocampus",
abstract = "The present study demonstrates cell-specific and developmental regulation of 5' and 3' splicing of the N-methyl-D-aspartate receptor NR1 subunit within specific neuronal populations of the hippocampus. At birth, NR1 transcripts lacking exon 5 (encoding the amino-terminal splice cassette N1) exhibit mature patterns of labelling within the hippocampus, with high levels of expression in the CA1, CA3, and dentate gyrus. In contrast, exon 5-containing (NR1(1XX)) transcripts are expressed at low levels until P8, at which time expression is prominent and essentially uniform in the CA1, CA3, and dentate gyrus. Exon 5 expression increases at a faster rate in CA3 than in CA1. or dentate gyrus. By the third week postnatal (postnatal day P21), exon 5-containing transcripts exhibit a distinct gradient of labelling, with more intense expression in CA3, than in CA1 or dentate gyrus. By P21 pyramidal neurons of the CA1 and granule cells of the dentate gyrus express mainly NR12(0xx) receptor messenger RNAs (lacking exon 5). Because splicing in of the N1 splice cassette confers greater current amplitude and enhanced potentiation by protein kinase C, these observations predict elevated levels of synaptic activity in the CA1 early in postnatal life, a time at which synaptic plasticity is enhanced. The carboxy-terminal splice cassettes C1 and C2 are regulated independently within the hippocampus. Whereas NR(X11) (C1-C2-containing) and NR1(X01) (C2 only) receptors exhibit high levels of expression in CA1, CA3, and dentate gyrus, NR1(X01) receptors are expressed more intensely in pyramidal neurons of CA3. NR1(X10) receptor expression is very low in all cells and at all times examined, even in adults. Because splicing in of the C1 cassette is thought to regulate receptor targeting, clustering, and cytoskeletal interactions, N-methyl-D-aspartate receptors in the two hippocampal subfields may play differing roles in synaptogenesis and the formation of new neuronal contacts. Moreover, cell-specific patterns of NR(x00) receptor messenger RNAs parallel those of NR1(0XX) receptor messenger RNAs; and cell-specific patterns of NR1(1XX) (N1-containing) receptor messenger RNAs parallels those of NR1(X00) (C1-, C2-lacking) receptor messenger RNAs throughout development. These observations suggest that NR1(X00) receptors, which exhibits the greatest potentiation by protein kinase C, are likely to be important in CA1 during the second and third weeks postnatal. Cell-specific expression of NR1 splice variants undoubtedly contributes to functional diversity of N-methyl-D-aspartate receptor properties in neuronal populations within the hippocampus. Developmental regulation of NR1 splicing is likely to influence synaptic plasticity and the formation of new synaptic contacts. Moreover, findings from this study suggest that a change in NR1 splicing following a neurological injury could significantly alter glutamate pathogenicity in a particular population of cells.",
keywords = "Development regulation, Excitatory amino acid receptor, In situ hybridization, Neuroanatomy, NMDA receptor splice variant, RNA splicing",
author = "Paupard, {M. C.} and Friedman, {L. K.} and Zukin, {R. Suzanne}",
year = "1997",
month = "5",
day = "12",
doi = "10.1016/S0306-4522(96)00677-X",
language = "English (US)",
volume = "79",
pages = "399--409",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Developmental regulation and cell-specific expression of N-methyl-D-aspartate receptor splice variants in rat hippocampus

AU - Paupard, M. C.

AU - Friedman, L. K.

AU - Zukin, R. Suzanne

PY - 1997/5/12

Y1 - 1997/5/12

N2 - The present study demonstrates cell-specific and developmental regulation of 5' and 3' splicing of the N-methyl-D-aspartate receptor NR1 subunit within specific neuronal populations of the hippocampus. At birth, NR1 transcripts lacking exon 5 (encoding the amino-terminal splice cassette N1) exhibit mature patterns of labelling within the hippocampus, with high levels of expression in the CA1, CA3, and dentate gyrus. In contrast, exon 5-containing (NR1(1XX)) transcripts are expressed at low levels until P8, at which time expression is prominent and essentially uniform in the CA1, CA3, and dentate gyrus. Exon 5 expression increases at a faster rate in CA3 than in CA1. or dentate gyrus. By the third week postnatal (postnatal day P21), exon 5-containing transcripts exhibit a distinct gradient of labelling, with more intense expression in CA3, than in CA1 or dentate gyrus. By P21 pyramidal neurons of the CA1 and granule cells of the dentate gyrus express mainly NR12(0xx) receptor messenger RNAs (lacking exon 5). Because splicing in of the N1 splice cassette confers greater current amplitude and enhanced potentiation by protein kinase C, these observations predict elevated levels of synaptic activity in the CA1 early in postnatal life, a time at which synaptic plasticity is enhanced. The carboxy-terminal splice cassettes C1 and C2 are regulated independently within the hippocampus. Whereas NR(X11) (C1-C2-containing) and NR1(X01) (C2 only) receptors exhibit high levels of expression in CA1, CA3, and dentate gyrus, NR1(X01) receptors are expressed more intensely in pyramidal neurons of CA3. NR1(X10) receptor expression is very low in all cells and at all times examined, even in adults. Because splicing in of the C1 cassette is thought to regulate receptor targeting, clustering, and cytoskeletal interactions, N-methyl-D-aspartate receptors in the two hippocampal subfields may play differing roles in synaptogenesis and the formation of new neuronal contacts. Moreover, cell-specific patterns of NR(x00) receptor messenger RNAs parallel those of NR1(0XX) receptor messenger RNAs; and cell-specific patterns of NR1(1XX) (N1-containing) receptor messenger RNAs parallels those of NR1(X00) (C1-, C2-lacking) receptor messenger RNAs throughout development. These observations suggest that NR1(X00) receptors, which exhibits the greatest potentiation by protein kinase C, are likely to be important in CA1 during the second and third weeks postnatal. Cell-specific expression of NR1 splice variants undoubtedly contributes to functional diversity of N-methyl-D-aspartate receptor properties in neuronal populations within the hippocampus. Developmental regulation of NR1 splicing is likely to influence synaptic plasticity and the formation of new synaptic contacts. Moreover, findings from this study suggest that a change in NR1 splicing following a neurological injury could significantly alter glutamate pathogenicity in a particular population of cells.

AB - The present study demonstrates cell-specific and developmental regulation of 5' and 3' splicing of the N-methyl-D-aspartate receptor NR1 subunit within specific neuronal populations of the hippocampus. At birth, NR1 transcripts lacking exon 5 (encoding the amino-terminal splice cassette N1) exhibit mature patterns of labelling within the hippocampus, with high levels of expression in the CA1, CA3, and dentate gyrus. In contrast, exon 5-containing (NR1(1XX)) transcripts are expressed at low levels until P8, at which time expression is prominent and essentially uniform in the CA1, CA3, and dentate gyrus. Exon 5 expression increases at a faster rate in CA3 than in CA1. or dentate gyrus. By the third week postnatal (postnatal day P21), exon 5-containing transcripts exhibit a distinct gradient of labelling, with more intense expression in CA3, than in CA1 or dentate gyrus. By P21 pyramidal neurons of the CA1 and granule cells of the dentate gyrus express mainly NR12(0xx) receptor messenger RNAs (lacking exon 5). Because splicing in of the N1 splice cassette confers greater current amplitude and enhanced potentiation by protein kinase C, these observations predict elevated levels of synaptic activity in the CA1 early in postnatal life, a time at which synaptic plasticity is enhanced. The carboxy-terminal splice cassettes C1 and C2 are regulated independently within the hippocampus. Whereas NR(X11) (C1-C2-containing) and NR1(X01) (C2 only) receptors exhibit high levels of expression in CA1, CA3, and dentate gyrus, NR1(X01) receptors are expressed more intensely in pyramidal neurons of CA3. NR1(X10) receptor expression is very low in all cells and at all times examined, even in adults. Because splicing in of the C1 cassette is thought to regulate receptor targeting, clustering, and cytoskeletal interactions, N-methyl-D-aspartate receptors in the two hippocampal subfields may play differing roles in synaptogenesis and the formation of new neuronal contacts. Moreover, cell-specific patterns of NR(x00) receptor messenger RNAs parallel those of NR1(0XX) receptor messenger RNAs; and cell-specific patterns of NR1(1XX) (N1-containing) receptor messenger RNAs parallels those of NR1(X00) (C1-, C2-lacking) receptor messenger RNAs throughout development. These observations suggest that NR1(X00) receptors, which exhibits the greatest potentiation by protein kinase C, are likely to be important in CA1 during the second and third weeks postnatal. Cell-specific expression of NR1 splice variants undoubtedly contributes to functional diversity of N-methyl-D-aspartate receptor properties in neuronal populations within the hippocampus. Developmental regulation of NR1 splicing is likely to influence synaptic plasticity and the formation of new synaptic contacts. Moreover, findings from this study suggest that a change in NR1 splicing following a neurological injury could significantly alter glutamate pathogenicity in a particular population of cells.

KW - Development regulation

KW - Excitatory amino acid receptor

KW - In situ hybridization

KW - Neuroanatomy

KW - NMDA receptor splice variant

KW - RNA splicing

UR - http://www.scopus.com/inward/record.url?scp=0030958288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030958288&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(96)00677-X

DO - 10.1016/S0306-4522(96)00677-X

M3 - Article

C2 - 9200724

AN - SCOPUS:0030958288

VL - 79

SP - 399

EP - 409

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 2

ER -