A model of long-term memory storage in the cerebellar cortex: A possible role for plasticity at parallel fiber synapses onto stellate/basket interneurons

By evoking changes in climbing fiber activity, movement errors are thought to modify synapses from parallel fibers onto Purkinje cells (pf*Pkj) so as to improve subsequent motor performance. Theoretical arguments suggest there is an intrinsic tradeoff, however, between motor adaptation and long-term storage. Assuming a baseline rate of motor errors is always present, then repeated performance of any learned movement will generate a series of climbing fiber-mediated corrections. By reshuffling the synaptic weights responsible for any given movement, such corrections will degrade the memories for other learned movements stored in overlapping sets of synapses. The present paper shows that long-term storage can be accomplished by a second site of plasticity at synapses from parallel fibers onto stellate/basket interneurons (pf*St/Bk). Plasticity at pf*St/Bk synapses can be insulated from ongoing fluctuations in climbing fiber activity by assuming that changes in pf*St/Bk synapses occur only after changes in pf*Pkj synapses have built up to a threshold level. Although climbing fiber-dependent plasticity at pf*Pkj synapses allows for the exploration of novel motor strategies in response to changing environmental conditions, plasticity at pf*St/Bk synapses transfers successful strategies to stable long-term storage. To quantify this hypothesis, both sites of plasticity are incorporated into a dynamical model of the cerebellar cortex and its interactions with the inferior olive. When used to simulate idealized motor conditioning trials, the model predicts that plasticity develops first at pf*Pkj synapses, but with additional training is transferred to pf*St/Bk synapses for long-term storage.

Hypothesis: "Rogue cell"-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis.

The hemagglutination inhibition antibody titers against the JC and BK polyoma viruses (JCV and BKV, respectively) are significantly elevated in individuals exhibiting "rogue" cells among their cultured lymphocytes. However, the elevation is so much greater with respect to JCV that the BKV elevation could readily be explained by cross reactivity to the capsid protein of these two closely related viruses. The JCV exhibits high sequence homology with the simian papovavirus, simian virus 40 (SV40), and inoculation of human fetal brain cells with JCV produces polyploidy and chromosomal damage very similar to that produced by SV40. We suggest, by analogy with the effects of SV40, that these changes are due to the action of the viral large tumor antigen, a pluripotent DNA binding protein that acts in both transcription and replication. The implications of these findings for oncogenesis are briefly discussed.

Identification of receptor ligands and receptor subtypes using antagonists in a capillary electrophoresis single-cell biosensor separation system.

A capillary electrophoresis system with single-cell biosensors as a detector has been used to separate and identify ligands in complex biological samples. The power of this procedure was significantly increased by introducing antagonists that inhibited the cellular response from selected ligand-receptor interactions. The single-cell biosensor was based on the ligand-receptor binding and G-protein-mediated signal transduction pathways in PC12 and NG108-15 cell lines. Receptor activation was measured as increases in cytosolic free calcium ion concentration by using fluorescence microscopy with the intracellular calcium ion indicator fluo-3-acetoxymethyl ester. Specifically, a mixture of bradykinin (BK) and acetylcholine (ACh) was fractionated and the components were identified by inhibiting the cellular response with icatibant (HOE 140), a selective antagonist to the BK B2 receptor subtype (B2BK), and atropine, an antagonist to muscarinic ACh receptor subtypes. Structurally related forms of BK were also identified based on inhibiting B2BK receptors. Applications of this technique include identification of endogenous BK in a lysate of human hepatocellular carcinoma cells (Hep G2) and screening for bioactivity of BK degradation products in human blood plasma. The data demonstrate that the use of antagonists with a single-cell biosensor separation system aids identification of separated components and receptor subtypes.

Library catalogue notes of Isaac Smith, ca. 1789

Thirteen slips of paper with fragments of handwritten alphabetical lists created by Isaac Smith presumably in his capacity as Harvard Librarian. Most of the entries are surnames or single-word subjects. For example, one slip with "M" entries includes: milway, miracles, miraculous, Mitchell, and Mitchell. Some of the lists have struck-through words or have entries annotated with numbers and the abbreviations "o" and "bk." The verso of one leaf has a brief, undated note regarding the transfer of books between Mr. Hilliard and Mr. Smith.

Americans with Disabilities Act handbook.

"October 1992."

Glass beads for highway paint stripes.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Twelve sonatas for the piano. [music] /

bk.1. 1-7 -- bk.2. 8-12.

Hungarian dances. [music] /

Bk.1. Nos. 1-5 -- Bk.2. Nos. 6-10.

The complete works in verse and prose of Edmund Spenser /

Vol. 10 ("Glossarial index, with notes and illustrations on every word, person and thing, in the entire works") never published?

Apollo in chorus.

Copyright by William Binney Smith.

Public speaking /

Added t.p.: Public speaking : the standard course of the United Y.M.C.A. schools.

Follow-up study: floating glass beads for traffic stripes. Final report.

Mode of access: Internet.

Sebastiani Serlii Bononiensis De architectvra libri qvinqve ... : necnon extraordinarius quinquaginta portarum libellus in operis calce adiunctus hic demum conspicitur /

Errata, p. [449].

Healthy living,

Book 1 contains a chapter on "Physical exercises," book 2 a chapter on "Sport and health," by Walter Camp. Supplements in book one and two, by Oscar Dowling.

A Digest of English civil law /

Includes index.