Home LiteratureArticle Details
PMID: 8656293 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of NGF and NT3 mRNAs in hippocampal interneurons innervated by the GABAergic septohippocampal pathway.

Rocamora N, Pascual M, Acsàdy L, de Lecea L, Freund TF, Soriano E

Abstract

We used in situ hybridization for the detection of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT3) mRNAs combined with immunocytochemistry against the calcium-binding proteins parvalbumin (PARV), calbindin 28k (CALB), and calretinin (CALR) to determine the expression of neurotrophins in functionally distinct subsets of hippocampal interneurons. Most PARV-immunoreactive neurons in the hippocampus were NGF mRNA-positive (82%), which corresponds to 71% of NGF-positive neurons in the hippocampus proper and in the dentate gyrus (excluding granule cells). In contrast, only a subset of CALB- and CALR-immunoreactive interneurons (24% and 23%, respectively) displayed hybridization signals for NGF. Small subsets of PARV- and CALR-positive cells expressed NT3 mRNA, but we did not find hippocampal interneurons expressing BDNF mRNA. These results show that NGF and NT3 genes are differentially regulated in distinct subsets of GABAergic cells, and these interneurons are a major source of NGF production in the hippocampus. We also addressed whether hippocampal interneurons expressing neurotrophins were targets of the GABAergic septohippocampal pathway. We developed a triple-labeling method that combines anterograde tracing of this pathway by means of Phaseolus vulgaris leucoagglutinin injections, with in situ hybridization for the detection of neurotrophins, and immunocytochemistry for calcium-binding proteins. Virtually every PARV-positive neuron innervated by GABAergic septohippocampal baskets expressed NGF mRNA (86%), whereas 39-59% of CALR- and CALB-positive interneurons that were contacted by GABAergic septohippocampal axons showed NGF gene expression. A small subset of NT3 mRNA-expressing interneurons was also innervated by septohippocampal baskets. These findings show that the GABAergic septohippocampal pathway preferentially terminates on interneurons expressing NGF mRNA, suggesting that this neurotrophic factor might be involved in the specification of this connection and in its maintenance and normal function in the adult brain.

MeSH Terms
Afferent Pathways Animals Axons/chemistry Base Sequence Biomarkers Brain-Derived Neurotrophic Factor Cholinergic Fibers/chemistry,physiology Hippocampus/cytology Immunohistochemistry In Situ Hybridization Interneurons/cytology,physiology Molecular Sequence Data Nerve Growth Factors/analysis,genetics Nerve Tissue Proteins/analysis Neurotrophin 3 Phytohemagglutinins RNA, Messenger/physiology Rats Rats, Wistar Septal Nuclei/cytology gamma-Aminobutyric Acid/physiology
Chemicals
Biomarkers Brain-Derived Neurotrophic Factor Nerve Growth Factors Nerve Tissue Proteins Neurotrophin 3 Phytohemagglutinins RNA, Messenger leukoagglutinins, plants gamma-Aminobutyric Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rocamora N
Department of Animal and Plant Cell Biology, Faculty of Biology, University of Barcelona, Spain.
Pascual M
Acsàdy L
de Lecea L
Freund T F
Soriano E
References (96)
96 references, click to expand
  1. BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF.
    Neuron. 1991 Jun;6(6):937-48 PMID: 2054188
  2. Characterization of a polyclonal antiserum against the purified human recombinant calcium binding protein calretinin.
    Cell Calcium. 1993 Oct;14(9):639-48 PMID: 8242719
  3. Positive feedback between acetylcholine and the neurotrophins nerve growth factor and brain-derived neurotrophic factor in the rat hippocampus.
    Eur J Neurosci. 1994 Apr 1;6(4):668-71 PMID: 8025717
  4. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF.
    Science. 1990 Mar 23;247(4949 Pt 1):1446-51 PMID: 2321006
  5. p75 and Trk: a two-receptor system.
    Trends Neurosci. 1995 Jul;18(7):321-6 PMID: 7571013
  6. GABAergic and cholinergic neurons exhibit high-affinity nerve growth factor binding in rat basal forebrain.
    Exp Neurol. 1989 May;104(2):181-5 PMID: 2707365
  7. Calbindin D28k-containing nonpyramidal cells in the rat hippocampus: their immunoreactivity for GABA and projection to the medial septum.
    Neuroscience. 1992 Aug;49(4):793-805 PMID: 1279455
  8. High-affinity nerve growth factor receptor (Trk) immunoreactivity is localized in cholinergic neurons of the basal forebrain and striatum in the adult rat brain.
    Brain Res. 1993 May 28;612(1-2):330-5 PMID: 8330208
  9. Colocalization of NGF receptor immunoreactivity and [3H]GABA uptake activity in developing rat septum/diagonal band neurons in vitro.
    Neurosci Lett. 1989 Apr 24;99(1-2):39-43 PMID: 2546109
  10. Loss of developing cholinergic basal forebrain neurons following excitotoxic lesions of the hippocampus: rescue by neurotrophins.
    Exp Neurol. 1994 Dec;130(2):178-95 PMID: 7867749
  11. Calbindin D-28k and parvalbumin in the rat nervous system.
    Neuroscience. 1990;35(2):375-475 PMID: 2199841
  12. Death of developing septal cholinergic neurons following NGF withdrawal in vitro: protection by protein synthesis inhibition.
    J Neurosci. 1994 Jan;14(1):75-87 PMID: 8283253
  13. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us.
    Cell. 1994 Jun 3;77(5):627-38 PMID: 8205613
  14. Innervation of different peptide-containing neurons in the hippocampus by GABAergic septal afferents.
    Neuroscience. 1990;37(1):31-44 PMID: 1978740
  15. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons.
    Cell. 1994 Mar 25;76(6):1001-11 PMID: 8137419
  16. Rat beta-nerve growth factor sequence and site of synthesis in the adult hippocampus.
    J Neurosci Res. 1988 Aug;20(4):403-10 PMID: 3184206
  17. GABAergic neurons containing the Ca2+-binding protein parvalbumin in the rat hippocampus and dentate gyrus.
    Brain Res. 1987 Sep 1;419(1-2):119-30 PMID: 3315112
  18. Differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs in adult rat brain after intrahippocampal injection of quinolinic acid.
    Brain Res Mol Brain Res. 1994 Oct;26(1-2):89-98 PMID: 7854071
  19. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene.
    Nature. 1994 Mar 17;368(6468):246-9 PMID: 8145823
  20. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements.
    Nature. 1994 Mar 17;368(6468):249-51 PMID: 8145824
  21. Induction of L1 mRNA in PC12 cells by NGF is modulated by cell-cell contact and does not require the high-affinity NGF receptor.
    J Neurosci. 1995 Mar;15(3 Pt 2):2504-12 PMID: 7891184
  22. Reduced transport of [125I]nerve growth factor by cholinergic neurons and down-regulated TrkA expression in the medial septum of aged rats.
    Neuroscience. 1994 Oct;62(3):625-9 PMID: 7532836
  23. Fine structure of rat septohippocampal neurons: II. A time course analysis following axotomy.
    J Comp Neurol. 1992 Nov 8;325(2):219-42 PMID: 1460114
  24. Cholinergic innervation of hippocampal GAD- and somatostatin-immunoreactive commissural neurons.
    J Comp Neurol. 1987 Jul 1;261(1):33-47 PMID: 2887594
  25. Is there a long-lasting effect of a short-term nerve growth factor application on axotomized rat septohippocampal neurons?
    Neurosci Lett. 1994 May 23;173(1-2):213-5 PMID: 7936417
  26. An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L).
    Brain Res. 1984 Jan 9;290(2):219-38 PMID: 6198041
  27. The parvalbumin-containing nonpyramidal neurons in the rat hippocampus.
    Anat Embryol (Berl). 1990;181(5):413-25 PMID: 2196836
  28. Subpopulations of GABAergic neurons containing parvalbumin, calbindin D28k, and cholecystokinin in the rat hippocampus.
    J Comp Neurol. 1991 Oct 15;312(3):371-8 PMID: 1721075
  29. GABAergic septohippocampal neurons contain parvalbumin.
    Brain Res. 1989 Jan 30;478(2):375-81 PMID: 2924136
  30. Calretinin is present in non-pyramidal cells of the rat hippocampus--I. A new type of neuron specifically associated with the mossy fibre system.
    Neuroscience. 1992;48(1):1-27 PMID: 1584417
  31. A high degree of spatial selectivity in the axonal and dendritic domains of physiologically identified local-circuit neurons in the dentate gyrus of the rat hippocampus.
    Eur J Neurosci. 1993 May 1;5(5):395-410 PMID: 8261117
  32. Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections.
    J Neurosci. 1986 Aug;6(8):2155-62 PMID: 3746405
  33. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF.
    Nature. 1993 May 27;363(6427):350-3 PMID: 8497318
  34. Atrophy but not death of adult septal cholinergic neurons after ablation of target capacity to produce mRNAs for NGF, BDNF, and NT3.
    J Neurosci. 1993 Dec;13(12):5263-76 PMID: 8254373
  35. Immunocytochemical study of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat hippocampus.
    Exp Brain Res. 1988;72(2):347-62 PMID: 3066634
  36. Spiny nonpyramidal neurons in the CA3 region of the rat hippocampus are glutamate-like immunoreactive and receive convergent mossy fiber input.
    J Comp Neurol. 1993 Jul 15;333(3):435-48 PMID: 8102385
  37. Distribution of septohippocampal neurons containing parvalbumin or choline acetyltransferase in the rat brain.
    J Comp Neurol. 1990 Aug 15;298(3):362-72 PMID: 2212109
  38. Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: response to fimbria-fornix transection.
    J Comp Neurol. 1989 Jun 8;284(2):187-204 PMID: 2546981
  39. Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression.
    J Neurosci. 1993 May;13(5):1965-75 PMID: 8478687
  40. Expression of members of the trk family in the developing postnatal rat brain.
    Brain Res Dev Brain Res. 1993 Mar 19;72(1):119-31 PMID: 8453762
  41. Stratum lacunosum-moleculare interneurons of hippocampal CA1 region. II. Intrasomatic and intradendritic recordings of local circuit synaptic interactions.
    J Neurosci. 1988 Apr;8(4):1411-24 PMID: 3357024
  42. Regulation of TrkA and ChAT expression in developing rat basal forebrain: evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons.
    J Neurosci. 1995 Apr;15(4):2888-905 PMID: 7536822
  43. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.
    Science. 1995 Mar 17;267(5204):1658-62 PMID: 7886457
  44. Tonic inhibition originates from synapses close to the soma.
    Neuron. 1995 Jun;14(6):1273-83 PMID: 7605636
  45. The organization of the embryonic and early postnatal murine hippocampus. II. Development of entorhinal, commissural, and septal connections studied with the lipophilic tracer DiI.
    J Comp Neurol. 1994 Jun 1;344(1):101-20 PMID: 8063952
  46. Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system.
    J Neurosci. 1994 Jan;14(1):14-28 PMID: 8283230
  47. TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons.
    J Neurosci. 1995 Feb;15(2):1567-76 PMID: 7869118
  48. Precision and variability in postsynaptic target selection of inhibitory cells in the hippocampal CA3 region.
    Eur J Neurosci. 1993 Dec 1;5(12):1729-51 PMID: 8124523
  49. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain.
    EMBO J. 1990 Aug;9(8):2459-64 PMID: 2369898
  50. GABAergic innervation of the rat fascia dentata: a novel type of interneuron in the granule cell layer with extensive axonal arborization in the molecular layer.
    J Comp Neurol. 1993 Aug 15;334(3):385-96 PMID: 8376624
  51. Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons.
    Science. 1995 Jun 9;268(5216):1495-9 PMID: 7770776
  52. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture.
    Neuron. 1990 Sep;5(3):297-306 PMID: 2169269
  53. Septal cholinergic afferents regulate expression of brain-derived neurotrophic factor and beta-nerve growth factor mRNA in rat hippocampus.
    Exp Brain Res. 1992;88(1):78-90 PMID: 1541364
  54. Calretinin is present in non-pyramidal cells of the rat hippocampus--III. Their inputs from the median raphe and medial septal nuclei.
    Neuroscience. 1993 Feb;52(4):829-41 PMID: 7680801
  55. Septal neurons containing glutamic acid decarboxylase immunoreactivity project to the hippocampal region in the rat brain.
    Anat Embryol (Berl). 1984;169(1):41-4 PMID: 6721220
  56. Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus.
    Brain Res Mol Brain Res. 1991 Jan;9(1-2):113-23 PMID: 1708074
  57. Development of the rat septohippocampal projection: tracing with DiI and electron microscopy of identified growth cones.
    J Comp Neurol. 1993 Jun 1;332(1):69-88 PMID: 7685781
  58. Neurotrophic factors. Switching neurotrophin dependence.
    Curr Biol. 1994 Mar 1;4(3):273-6 PMID: 7922335
  59. Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):961-5 PMID: 1992488
  60. Survival of newly postmitotic motoneurons is transiently independent of exogenous trophic support.
    J Neurosci. 1995 Apr;15(4):3128-37 PMID: 7722651
  61. Limbic seizures induce a differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3, in the rat hippocampus.
    Brain Res Mol Brain Res. 1992 Mar;13(1-2):27-33 PMID: 1315916
  62. Mice lacking brain-derived neurotrophic factor develop with sensory deficits.
    Nature. 1994 Mar 10;368(6467):147-50 PMID: 8139657
  63. Calretinin is present in non-pyramidal cells of the rat hippocampus--II. Co-existence with other calcium binding proteins and GABA.
    Neuroscience. 1992;48(1):29-43 PMID: 1584423
  64. TrkA-immunoreactive profiles in the central nervous system: colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin.
    J Comp Neurol. 1994 Dec 22;350(4):587-611 PMID: 7890832
  65. The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons.
    Neuron. 1992 May;8(5):983-93 PMID: 1375039
  66. Postsynaptic targets of GABAergic hippocampal neurons in the medial septum-diagonal band of broca complex.
    J Neurosci. 1993 Sep;13(9):3712-24 PMID: 7690065
  67. Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors.
    EMBO J. 1990 Nov;9(11):3545-50 PMID: 2170117
  68. Brain-derived neurotrophic factor promotes the differentiation of various hippocampal nonpyramidal neurons, including Cajal-Retzius cells, in organotypic slice cultures.
    J Neurosci. 1996 Jan 15;16(2):675-87 PMID: 8551351
  69. In situ hybridization detection of trkA mRNA in brain: distribution, colocalization with p75NGFR and up-regulation by nerve growth factor.
    J Comp Neurol. 1994 Mar 15;341(3):324-39 PMID: 8195465
  70. Brain-derived neurotrophic factor: subcellular compartmentalization and interneuronal transfer as visualized with anti-peptide antibodies.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9843-7 PMID: 1946410
  71. Development of septal cholinergic neurons in culture: plating density and glial cells modulate effects of NGF on survival, fiber growth, and expression of transmitter-specific enzymes.
    J Neurosci. 1988 Aug;8(8):2967-85 PMID: 2842468
  72. Nerve growth factor mRNA is expressed by GABAergic neurons in rat hippocampus.
    Neuroreport. 1993 Dec 13;5(3):273-6 PMID: 8298089
  73. The neurotrophic factor concept: a reexamination.
    J Neurosci. 1993 Jul;13(7):2739-48 PMID: 8331370
  74. A low-affinity nerve growth factor receptor antibody is internalized and retrogradely transported selectively into cholinergic neurons of the rat basal forebrain.
    Neuroscience. 1993 Nov;57(2):297-305 PMID: 8115039
  75. Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis.
    Neuron. 1991 Jul;7(1):165-76 PMID: 1829904
  76. Analysis of the trk NGF receptor tyrosine kinase using recombinant fusion proteins.
    J Cell Sci Suppl. 1993;17:223-8 PMID: 8144701
  77. Axo-axonic chandelier cells in the rat fascia dentata: Golgi-electron microscopy and immunocytochemical studies.
    J Comp Neurol. 1990 Mar 1;293(1):1-25 PMID: 1690225
  78. Transcripts encoding a neural membrane CD26 peptidase-like protein are stimulated by synaptic activity.
    Brain Res Mol Brain Res. 1994 Sep;25(3-4):286-96 PMID: 7808228
  79. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family.
    Neuron. 1990 Oct;5(4):511-26 PMID: 2206535
  80. Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites.
    Nature. 1994 Apr 28;368(6474):823-8 PMID: 8159242
  81. Muscarinic amplification of fast excitation in hilar neurones and inhibition in granule cells in the guinea-pig hippocampus.
    J Physiol. 1994 Nov 1;480 ( Pt 3):513-26 PMID: 7869265
  82. Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study.
    J Comp Neurol. 1985 Sep 8;239(2):237-46 PMID: 4044938
  83. Limbic seizures increase neuronal production of messenger RNA for nerve growth factor.
    Science. 1989 Aug 18;245(4919):758-61 PMID: 2549634
  84. Neurotrophin induced second messenger responses in rat brain synaptosomes.
    Neuroreport. 1993 May;4(5):483-6 PMID: 8390308
  85. Neurotrophins. Keeping track of changing neurotrophic theory.
    Curr Biol. 1994 Jul 1;4(7):662-5 PMID: 7953551
  86. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development.
    Cell. 1994 Mar 25;76(6):989-99 PMID: 8137432
  87. Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain.
    Exp Neurol. 1991 Oct;114(1):35-43 PMID: 1915733
  88. Cellular localization of NGF and NT-3 mRNAs in postnatal rat forebrain.
    Mol Cell Neurosci. 1994 Feb;5(1):46-62 PMID: 8087414
  89. Trophic factors and neuronal survival.
    Neuron. 1989 Jun;2(6):1525-34 PMID: 2697237
  90. GABA-containing neurons in the septum control inhibitory interneurons in the hippocampus.
    Nature. 1988 Nov 10;336(6195):170-3 PMID: 3185735
  91. Survival of adult basal forebrain cholinergic neurons after loss of target neurons.
    Science. 1990 Jan 19;247(4940):338-42 PMID: 1688664
  92. Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system.
    Neuroscience. 1992 Dec;51(3):513-32 PMID: 1488112
  93. Cholinergic regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) but not neurotrophin-3 (NT-3) mRNA levels in the developing rat hippocampus.
    J Neurosci. 1993 Sep;13(9):3818-26 PMID: 8366347
  94. Interplay between glutamate and gamma-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons.
    Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10037-41 PMID: 1658793
  95. Hippocampal pyramidal cells excite inhibitory neurons through a single release site.
    Nature. 1993 Dec 16;366(6456):683-7 PMID: 8259211
  96. Survival-promoting effect of NGF on in vitro septohippocampal neurons with cholinergic and GABAergic phenotypes.
    Brain Res Dev Brain Res. 1991 Feb 22;58(2):189-201 PMID: 1851468
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1996-06-15
Pages
3991-4004
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6578621
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com