Biochemistry of Information Storage in the Nervous System

Black, Ira B.; Adler, Joshua E.; Dreyfus, Cheryl F.; Friedman, Wilma; LaGamma, Edmund F.; Roach, Arthur

doi:10.1126/science.2884727

Cited by 145 publications

(47 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4). Induction of the TH gene by PKA might thus be an important mediator of alterations of neuronal activity in response to environmental stimuli (7). Additionally, PKA can exert important acute regulation of TH activity in response to many stimuli by phosphorylation of the enzyme molecule (3).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A dual role for the cAMP-dependent protein kinase in tyrosine hydroxylase gene expression.

Kim

Park

Wessel

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to 3,4-dihydroxy-L-phenylalanine, the first and rate-limiting step in catecholamine biosynthesis. The cAMP-dependent protein kinase (PKA) phosphorylates and activates the TH enzyme and is thought to mediate transcriptional induction of the TH gene. To better understand the functional role of PKA in TH gene regulation, we studied TH gene expression at the transcriptional, translational, and posttranslational levels in several PKA-deficient cell lines derived from rat PC12 pheochromocytoma cells. Strikingly, all PKAdeficient cell lines analyzed in this study showed substantial deficits in basal TH expression as measured by TH enzymatic activity, level of TH immunoreactivity, TH protein level, and steady-state mRNA level. Interestingly, the steady-state level of mRNA correlated well with levels of TH activity, immunoreactivity, and protein. In addition, PKA-deficient cell lines lacked transcriptional induction of the TH gene following treatment with dibutyryl cAMP. Cotransfection of PKAdeficient cells with an expression plasmid for the catalytic subunit of PKA fully reversed transcriptional defect, as indicated by robust transcriptional induction of a reporter construct containing 2400 bp of TH upstream sequence in all PC12 cells tested. These data indicate that the PKA system regulates both the basal and the cAMP-inducible expression of the TH gene primarily at the transcriptional level in PC12 cells.The nervous system performs important adaptive processes through activation of various postsynaptic receptors and their associated signal transduction pathways. These processes can elicit either acute changes in the function of proteins-for instance, enzyme activities-by covalent modification ofpreexisting molecules or delayed changes in levels of protein by altering gene expression. The regulation of neurotransmitter-biosynthesizing-enzyme genes in particular is thought to play a pivotal role, since the resultant change in the amount of available neurotransmitter molecules can trigger substantial variations in neuronal activity.Tyrosine hydroxylase [TH; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] catalyzes the conversion of L-tyrosine to 3,4-dihydroxy-L-phenylalanine (L-dopa), which is the first and rate-limiting step in the biosynthesis of the catecholamine neurotransmitters (1). A variety of trans-synaptic and hormonal stimuli are known to produce either acute increases in TH activity via phosphorylation of the preexisting enzyme proteins (refs. 2 and 3; for review see ref. 4) or delayed increases in TH (5-7). The latter responses correlate with increases in TH mRNA and enzyme molecules and are blocked by inhibitors of RNA and protein synthesis, indicating that transcriptional regulation of the TH gene is directly involved (8,9).

show abstract

Section: Resultsmentioning

confidence: 99%

“…2 and 3; for review see ref. 4) or delayed increases in TH (5)(6)(7). The latter responses correlate with increases in TH mRNA and enzyme molecules and are blocked by inhibitors of RNA and protein synthesis, indicating that transcriptional regulation of the TH gene is directly involved (8,9).…”

mentioning

confidence: 99%

A dual role for the cAMP-dependent protein kinase in tyrosine hydroxylase gene expression.

Kim

Park

Wessel

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Depolarization, which leads to a rapid fourfold increase in VGF mRNA levels, triggers calcium influx through voltage-gated calcium channels. Genes regulated by depolarization include the immediate-early genes (9,37,75,76,82,107) and those encoding neuropeptide and neurotransmitter biosynthetic enzymes (12,31,50,103). Since VGF polypeptide is secreted through a regulated pathway in PC12 cells and its release is stimulated by depolarization (80), the elevation in VGF mRNA levels that was observed after depolarization may be a response to depletion of cellular VGF stores, much as the pituitary genes that encode growth hormone, pro-opiomelanocortin, and prolactin respond to stimulated secretion of the respective peptide hormones by increasing the rate of gene transcription (7,8,30,34,78).…”

Section: Discussionmentioning

confidence: 99%

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

1991

View full text Add to dashboard Cite

Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.

show abstract

“…Graybiel and Ragsdale (38) have found that butyryl-and acetylcholinesterase levels are also higher in regions of visual cortex deprived of input by unilateral enucleation. In culture systems as well, reductions in electrical activity may increase the expression of some neurotransmitter systems (39).…”

Section: Discussionmentioning

confidence: 99%

Neural plasticity without postsynaptic action potentials: less-active inputs become dominant when kitten visual cortical cells are pharmacologically inhibited.

Reiter

Stryker

1988

Proc. Natl. Acad. Sci. U.S.A.

244

140

View full text Add to dashboard Cite

Models of synaptic plasticity in the nervous system have conventionally assumed a mechanism in which spike activity of a postsynaptic cell enhances the efficacy of recently active presynaptic inputs. Making use of the prompt and dramatic response of the visual cortex to occlusion of vision in one eye during the critical period, we tested the role of postsynaptic activity in ocular dominance plasticity. To do so, we selectively blocked cortical cell discharges with a continuous intracortical infusion of the inhibitory neurotransmitter agonist muscimol during a period of monocular deprivation. This drug inhibits cortical cell discharges with no apparent effect on the activity of their presynaptic geniculocortical inputs. Recording from single cortical cells after they had recovered from the muscimol-induced blockade, we found a consistent shift in the responsiveness of the visual cortex in favor of the less-active, closed eye, while the normal shift in favor of the more-active, open eye was evident in regions not affected by the treatment. Such an inhibition-coupled expression of plasticity in favor of the less-active, closed eye cannot be explained by a nonspecific disruption of cortical function. We interpret these results to indicate (i) that the postsynaptic cell is crucially involved in plasticity of the visual cortex, (ii) that the direction of cortical plasticity depends on postsynaptic membrane conductance or polarization, and (iii) that plasticity can occur in the absence of postsynaptic spike activity.Synaptic plasticity is known to be widespread in both the developing and the mature central nervous system. A hypothesis about the mechanism of plasticity in development, put forward by Hebb, is that spike activity in the postsynaptic cell enhances the efficacy of recently active inputs (1-6). Hebb's hypothesis has been used to explain many instances of neural plasticity (7). This hypothesis stands in contrast to one favoring a purely presynaptic mechanism, as was reported for classical conditioning in Aplysia, in which responses of cells were facilitated even while their somata were hyperpolarized by an intracellular microelectrode (8).In the visual (9-14) and motor cortices (15), however, several types of evidence favor an excitation-coupled postsynaptic mechanism of plasticity.Synaptic connections serving the two eyes to the visual cortex are reorganized during normal development (16-18).This reorganization is most dramatic when vision in one eye is occluded during a critical period in early life (17)(18)(19)(20): the occluded eye loses its ability to drive most cortical cells, which come to respond exclusively to the nonoccluded eye. This phenomenon is called ocular dominance plasticity.Previous experiments in which a region of visual cortex was infused with tetrodotoxin during a period of monocular deprivation demonstrated that activity at the level of the visual cortex is crucial for ocular dominance plasticity (10). Because tetrodotoxin blocks pre-as well as postsynaptic activities in the vis...

show abstract

Biochemistry of Information Storage in the Nervous System

Cited by 145 publications

References 41 publications

A dual role for the cAMP-dependent protein kinase in tyrosine hydroxylase gene expression.

A dual role for the cAMP-dependent protein kinase in tyrosine hydroxylase gene expression.

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

Neural plasticity without postsynaptic action potentials: less-active inputs become dominant when kitten visual cortical cells are pharmacologically inhibited.

Contact Info

Product

Resources

About