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Biomedical subjects

C Pittenger

Publications and source records attributed to C Pittenger.

6 recordsLinked to original sources
PubMed2001

Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase.

Long-lasting forms of synaptic plasticity like the late phase of LTP (L-LTP) typically require an elevation of cAMP, the recruitment of the cAMP-dependent protein kinase (PKA), and ultimately the activation of transcription and translation; some forms also require brain-derived neurotrophic factor (BDNF). Both cAMP and BDNF can activate mitogen-activated protein kinase (MAPK/ERK), which also plays a role in LTP. However, little is known about the mechanisms whereby cAMP, BDNF, and MAPK interact. We find that increases in cAMP can rapidly activate the BDNF receptor TrkB and induce BDNF-dependent long-lasting potentiation at the Schaffer collateral-CA1 synapse in hippocampus. Surprisingly, in these BDNF-dependent forms of potentiation, which are also MAPK dependent, TrkB activation is not critical for the activation of MAPK but instead appears to modulate the subcellular distribution and nuclear translocation of the activated MAPK.

Active Transport, Cell Nucleus↗
PubMed1999

The past, the future and the biology of memory storage.

We here briefly review a century of accomplishments in studying memory storage and delineate the two major questions that have dominated thinking in this area: the systems question of memory, which concerns where in the brain storage occurs; and the molecular question of memory, which concerns the mechanisms whereby memories are stored and maintained. We go on to consider the themes that memory research may be able to address in the 21st century. Finally, we reflect on the clinical and societal import of our increasing understanding of the mechanisms of memory, discussing possible therapeutic approaches to diseases that manifest with disruptions of learning and possible ethical implication of the ability, which is on the horizon, to ameliorate or even enhance human memory.

Animals↗
PubMed1995

Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair gene.

We have constructed a strain of Saccharomyces cerevisiae with a deletion of the YKL510 open reading frame, which was initially identified in chromosome XI as a homolog of the RAD2 nucleotide excision repair gene (A. Jacquier, P. Legrain, and B. Dujon, Yeast 8:121-132, 1992). The mutant strain exhibits increased sensitivity to UV light and to the alkylating agent methylmethane sulfonate but not to ionizing radiation. We have renamed the YKL510 open reading frame the RAD27 gene, in keeping with the accepted nomenclature for radiation-sensitive yeast mutants. Epistasis analysis indicates that the gene is in the RAD6 group of genes, which are involved in DNA damage tolerance. The mutant strain also exhibits increased plasmid loss, increased spontaneous mutagenesis, and a temperature-sensitive lethality whose phenotype suggests a defect in DNA replication. Levels of the RAD27 gene transcript are cell cycle regulated in a manner similar to those for several other genes whose products are known to be involved in DNA replication. We discuss the possible role of Rad27 protein in DNA repair and replication.

Base Sequence↗
PubMedDate not supplied

A genetic switch for long-term memory.

Current models of brain function hold that learning corresponds to changes in the efficacy of single synapses. The study of learning and of a variety of forms of synaptic plasticity has revealed that both have at least two phases: an early phase that is not dependent on protein synthesis and a late phase that depends on new transcription and translation. Our laboratory has examined synaptic plasticity in Aplysia and in mice to better understand the regulatory events that lead to the induction of the late, protein synthesis-dependent phase of synaptic plasticity. Our recent studies of Aplysia have revealed that the genes that control the late phase of synaptic facilitation are controlled by both an activator, ApCREB1, and a repressor, ApCREB2. This leads to a model in which the late phase of synaptic facilitation is initiated by a perturbation of the balance between activators and repressors of transcription; this perturbation can be accomplished by regulating the activator, the repressor, or both. We, and others, have shown that this transcriptional switch is conserved, at least in part, in the regulation of synaptic plasticity in mice: CREB is implicated in activation of genes required for LTP, a model for synaptic plasticity in the mammalian hippocampus. We speculate that a similar balance between activators and repressors may regulate the genes required for long-term memory in mammals.

Animals↗