TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons

Holtzman, David M.; Kilbridge, Joshua; Li, Yiwen; Cunningham, Emmett T.; Lenn, Nicholas J.; Clary, Douglas O.; Reichardt, Louis F.; Mobley, William C.

doi:10.1523/jneurosci.15-02-01567.1995

Cited by 178 publications

(104 citation statements)

References 65 publications

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“…Immunostaining for NGF within the infusion site showed that exogenous NGF was con¢ned mainly to the cortical neuropil and seemed to avoid cortical neuronal cell bodies. We did not observe any TrkA immunoreactivity in cortical neurons (data not shown), and this is in agreement with other studies (Sobreviela et al, 1994;Holtzman et al, 1995). In addition, Domenici et al (1994b) found that the number of basal forebrain neurons labeled by a local injection of radiolabeled NGF into rat occipital cortex was one to two orders of magnitude greater than the number of labeled cortical neurons near the injection site, depending on the age of the animal.…”

Section: Possible Actions Of Ngf On Cortical Neuronssupporting

confidence: 92%

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Silver¹,

Fagiolini²,

Gillespie³

et al. 2001

Neuroscience

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AbstractöIntracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the e¡ects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF a¡ects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no e¡ect on the normal developmental segregation of geniculocortical a¡erents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75 NTR -, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons.We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: TrkA, p75, choline acetyltransferase, retrograde transport, acetylcholine, monocular deprivation.Monocular deprivation (MD) is a well-studied model of experience-dependent cortical plasticity. When one eye of an animal is occluded during a critical period of development, that eye loses most of its ability to drive neurons in primary visual cortex, shifting the distribution of visual responses to favor the nondeprived eye (Wiesel and Hubel, 1963). Intracerebroventricular (ICV) administration of the neurotrophin nerve growth factor (NGF) to rats during a critical period of development blocks the e¡ects of MD (Domenici et al., 1991;Ma¡ei et al., 1992). This has been demonstrated at several levels of analysis, including physiological, anatomical, immunocytochemical, and behavioral (for a review, see Cellerino and Ma¡ei, 1996). Infusion of NGF directly into developing rat visual cortex also prevents physiological ocular dominance plasticity (Lodovichi et al., 2000).In addition, anti-NGF antibodies prevent normal anatomical and physiological development of the visual system when they are administered to rats by implantation of antibody-secreting hybridoma cells in the lateral ventricle (Berardi et al., 1994). These antibodies also prolong the critical period for ocular dominance plasticity in the rat (Domenici et al., 1994a). Together, these results demonstrate an imp...

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Section: Possible Actions Of Ngf On Cortical Neuronssupporting

confidence: 92%

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Silver¹,

Fagiolini²,

Gillespie³

et al. 2001

Neuroscience

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“…This effect is likely mediated by activation of cortical TrkA, since the specific TrkA-activating antibody RTA also rescues LGN neurons from monocular deprivation-induced shrinkage (T. Pizzorusso, N. B. and L. M., unpublished) and prevents monocular deprivation effects in visual cortex . TrkA is not expressed by LGN neurons (Merlio et al, 1992;Holtzman et al, 1995), and LGN neurons do not retrogradely transport cortically infused NGF or RTA Pizzorusso et al, 1999). Rather, TrkA is expressed by cholinergic afferents (Merlio et al, 1992;Sobreviela et al, 1994;Holtzman et al, 1995;Rossi et al, 2002) and some cortical glutamatergic terminals (Sala et al, 1998).…”

Section: Ngf Accelerates Lgn Developmentmentioning

confidence: 99%

Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions

Wahle

Cristo²,

Schwerdtfeger

et al. 2003

Development

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Neurotrophins strongly affect visual system development and plasticity. However, the mode of delivery and targets of neurotrophin action are still under debate. For instance, cortical NT-4/5 (neurotrophin 4/5; Ntf4/5) was shown to rescue lateral geniculate nucleus (LGN) neurons from monocular deprivation-induced atrophy suggesting a retrograde action on thalamic afferents. It is still unclear whether LGN neurons respond to NT-4/5 and other neurotrophins during development in animals with normal vision. We now show that infusions of NT-4/5 and NGF (nerve growth factor) into visual cortex at the onset and the peak of the critical period accelerated LGN neuron growth. BDNF (brain-derived neurotrophic factor) was ineffective. The effects of neurotrophin on LGN development were clearly dissociated from the effects at cortical level because soma growth of cortical layer IV and VI neurons was strongly promoted by BDNF. NT-4/5 was only effective at the onset, but no longer at the peak of the critical period suggesting a switch in neurotrophin dependency for these cortical cell classes. To dissociate retrograde and anterograde effects of the TrkB ligands, we analyzed the stratum griseum superficiale (SGS) of the superior colliculus, a target of visual cortical efferents. Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth. Strikingly, the TrkB-expressing excitatory tectothalamic calbindin neurons in the SGS did not respond. This demonstrated for the first time a selective cell type-specific anterograde action of NT-4/5 and suggested for the LGN that anterograde as well as retrograde effects contribute to soma size regulation. Strikingly, cortical infusion of the cytokine LIF, which affects development of visual cortex neurochemical architecture, transiently inhibited growth of neurons in LGN,cortical layer IV and VI and SGS. In summary, the study presents three important results. First, central neurons regulate soma size development in an age-and ligand-specific fashion. Second, NT-4/5 and NGF accelerate LGN development in rats with normal vision while LIF delays growth. Third,anterogradely transported NT-4/5 effectively promotes neuronal maturation. These differential actions on subcortical neurons may contribute to the different effects of neurotrophins on visual system development and plasticity.

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“…Expression of trkA in sympathetic neurons starts at E13.5 and reaches highest levels at E18, coinciding with the time of their maximum response to NGF (Ernfors et al, 1992). In the central nervous system trkA mRNA has been found in NGFresponsive cholinergic neurons of the basal forebrain and neostriatum and in some non-cholinergic neurons in several nuclei at di erent regions of the brainstem (Holtzman et al, 1995). trkA expressing neurons closely match those that are NGF-dependent for survival and di erentiation, suggesting that trkA could mediate NGF actions in vivo.…”

mentioning

confidence: 98%

Molecular cloning and characterization of the 5′ region of the mouse trkA proto-oncogene

et al. 1999

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The trkA proto-oncogene encodes a high-a nity NGF receptor that is essential for the survival, di erentiation and maintenance of many neural and non-neural cell types. Altered expression of the trkA gene or trkA receptor malfunction have been implicated in neurodegeneration, tumor progression and oncogenesis. We have cloned and characterized the 5' region of the mouse trkA gene and have identi®ed its promoter. trkA promoter sequences are GC-rich, lack genuine TATA or CAAT boxes, and are contained within a CpG island which extends over the entire ®rst coding exon. The mouse trkA transcription start site is located 70/71 bp upstream to the AUG translation initiation codon. Sequence analysis showed that the gene encoding the insulin receptor-related receptor, IRR, is located just 1.6 kbp upstream to the trkA gene and is transcribed in the opposite direction. We have used trkA-CAT transcriptional fusions to study trkA promoter function in transient transfection experiments. RNase protection assays and CAT protein ELISA analyses showed that a 150 bp long DNA segment, immediately upstream to the start site, is su cient to direct accurate transcription in trkA-expressing cells. Dissection of this fragment allowed us to identify a 13 bp cis-regulatory element essential for both promoter activity and cell-type speci®c expression. Deletion of this 13 bp segment as well as modi®cation of its sequence by site-directed mutagenesis led to a dramatic decline in promoter activity. Gel mobility shift assays carried out with double-stranded oligonucleotides containing the 13 bp element revealed several speci®c DNA-protein complexes when nuclear extracts from trkA-expressing cells were used. Supershift experiments showed that the Sp1 transcription factor was a component of one of these complexes. Our results identify a minimal trkA gene promoter, located very close to the transcription start site, and de®ne a 13 bp enhancer within this promoter sequence.

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TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons

Cited by 178 publications

References 65 publications

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions

Molecular cloning and characterization of the 5′ region of the mouse trkA proto-oncogene

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