Biomedical subjects

J M Beggs

Publications and source records attributed to J M Beggs.

6 recordsLinked to original sources

PubMed2001

A statistical theory of long-term potentiation and depression.

The synaptic phenomena of long-term potentiation (LTP) and long-term depression (LTD) have been intensively studied for over twenty-five years. Although many diverse aspects of these forms of plasticity have been observed, no single theory has offered a unifying explanation for them. Here, a statistical "bin" model is proposed to account for a variety of features observed in LTP and LTD experiments performed with field potentials in mammalian cortical slices. It is hypothesized that long-term synaptic changes will be induced when statistically unlikely conjunctions of pre- and postsynaptic activity occur. This hypothesis implies that finite changes in synaptic strength will be proportional to information transmitted by conjunctions and that excitatory synapses will obey a Hebbian rule (Hebb, 1949). Using only one set of constants, the bin model offers an explanation as to why synaptic strength decreases in a decelerating manner during LTD induction (Mulkey & Malenka, 1992); why the induction protocols for LTP and LTD are asymmetric (Dudek & Bear, 1992; Mulkey & Malenka, 1992); why stimulation over a range of frequencies produces a frequency-response curve similar to that proposed by the BCM theory (Bienenstock, Cooper, & Munro, 1982; Dudek & Bear, 1992); and why this curve would shift as postsynaptic activity is changed (Kirkwood, Rioult, & Bear, 1996). In addition, the bin model offers an alternative to the BCM theory by predicting that changes in postsynaptic activity will produce vertical shifts in the curve rather than merely horizontal shifts.

Information Theory↗

PubMed2000

Gelonin is an unusual DNA glycosylase that removes adenine from single-stranded DNA, normal base pairs and mismatches.

We reported that plant ribosome inactivating proteins (RIP) have a unique DNA glycosylase activity that removes adenine from single-stranded DNA (Nicolas, E., Beggs, J. M., Haltiwanger, B. M., and Taraschi, T. F. (1998) J. Biol. Chem. 273, 17216-17220). In this investigation, we further characterized the interaction of the RIP gelonin with single-stranded oligonucleotides and investigated its activity on double-stranded oligonucleotides. At physiological pH, zinc and beta-mercaptoethanol stimulated the adenine DNA glycosylase activity of gelonin. Under these conditions, gelonin catalytically removed adenine from single-stranded DNA and, albeit to a lesser extent, from normal base pairs and mismatches in duplex DNA. Also unprecedented was the finding that activity on single-stranded and double-stranded oligonucleotides containing multiple adenines generated unstable products with several abasic sites, producing strand breakage and duplex melting, respectively. The results from competition experiments suggested similar interactions between gelonin's DNA-binding domain and oligonucleotides with and without adenine. A re-examination of the classification of gelonin as a DNA glycosylase/AP lyase using the borohydride trapping assay revealed that gelonin was similar to the DNA glycosylase MutY: both enzymes are monofunctional glycosylases, which are trappable to their DNA substrates. The k(cat) for the removal of adenine from single-stranded DNA was close to the values observed with multisubstrate DNA glycosylases, suggesting that the activity of RIPs on DNA may be physiologically relevant.

Adenine↗

PubMed2000

Prolonged synaptic integration in perirhinal cortical neurons.

Layer II/III of rat perirhinal cortex (PR) contains numerous late-spiking (LS) pyramidal neurons. When injected with a depolarizing current step, these LS cells typically delay spiking for one or more seconds from the onset of the current step and then sustain firing for the duration of the step. This pattern of delayed and sustained firing suggested a specific computational role for LS cells in temporal learning. This hypothesis predicts and requires that some layer II/III neurons should also exhibit delayed and sustained spiking in response to a train of excitatory synaptic inputs. Here we tested this prediction using visually guided, whole cell recordings from rat PR brain slices. Most LS cells (19 of 26) exhibited delayed spiking to synaptic stimulation (>1 s latency from the train onset), and the majority of these cells (13 of 19) also showed sustained firing that persisted for the duration of the synaptic train (5-10 s duration). Delayed and sustained firing in response to long synaptic trains has not been previously reported in vertebrate neurons. The data are consistent with our model that a circuit containing late spiking neurons can be used for encoding long time intervals during associative learning.

Animals↗

PubMed1998

A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific adenines in single-stranded DNA.

Although the biological function of DNA glycosylases is to protect the genome by removal of potentially cytotoxic or mutagenic bases, this investigation describes the existence of natural DNA glycosylases with activity on undamaged, nonmispaired bases. Gelonin, pokeweed antiviral protein, and ricin, previously described as ribosome-inactivating proteins, are shown to damage single-stranded DNA by removal of a protein-specific set of adenines and cleavage at the resulting abasic sites. Using an oligonucleotide as the substrate reveals that the reaction proceeds via the enzyme-DNA imino intermediate characteristic of DNA glycosylase/AP lyases. The adenine glycosylase activity on single-stranded DNA reported here challenges the concept that a normal base has to be in a mismatch to be specifically removed. By contrast to other glycosylases, these enzymes are expected to damage DNA rather than participate in repair processes. The significance of this DNase activity to the biological function of these plant proteins and to their toxicity to animal cells remains to be determined.

Adenine↗

PubMed1997

Direct evidence for the deoxyribonuclease activity of the plant ribosome inactivating protein gelonin.

Several plant ribotoxins, including gelonin, were reported to have additional weak nuclease activities on supercoiled DNA. The potential contribution of this activity to their cytotoxicity has not been given serious consideration due to concerns about contaminating nucleases in the protein preparations. We now report the degradation of single-stranded DNA by preparations of native plant gelonin and recombinant gelonin produced in E. coli. The DNase activity of both preparations is similarly modulated by zinc. An SDS-PAGE DNase assay identifies gelonin as the polypeptide responsible for deoxyribonuclease activity.

DNA, Single-Stranded↗

PubMed1994

Electrophysiology and morphology of neurons in rat perirhinal cortex.

The intrinsic membrane properties of perirhinal cortical neurons were studied by intracellular recording in in vitro rat brain slices. Gross morphology was also examined through injection of the fluorescent dye carboxyfluorescein. The cells encountered displayed a diversity of electrophysiological properties, and were similar to cells reported in other neocortical areas with regard to spiking patterns, afterpotentials, and morphology. However, very few (4%) intrinsically bursting neurons were encountered. Two pyramidal cells with thick apical dendrites were filled, and both fired doublets of action potentials for their first suprathreshold events. Of the filled pyramidal cells with thin apical dendrites, most (9/11) fired single action potentials for their first suprathreshold events. A variety of classification schemes were used to group the data, and several schemes were found to be equally successful. According to one of the schemes, cells recorded with carboxyfluorescein filled electrodes had significantly greater action potential widths at half-amplitude and more depolarized resting potentials than cells recorded without this dye.

Action Potentials↗