Neurobiology. In the article ''ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae '' by Steve A. N. Goldstein, Laura A. Price, David N. Rosenthal, and Mark H. Pausch, which appeared in number 23, November 12, 1996, of Proc. Natl. Acad. Sci. USA (93, 13256-13261), the authors request that the following sequence correction be noted. We have found errors in the ORK1 nucleotide sequence reported in this work. The correct sequence extends the ORF and predicts a protein of 1001 residues; the correct nucleotide and predicted protein sequences are deposited under the GenBank accession no. U55321. The errors do not otherwise alter the conclusions of the paper. We are grateful to Noam Zilberberg (Yale Univ. School of Medicine, New Haven, CT) for his efforts to establish the correct sequence.Neurobiology. In the article "A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia" by Hiroaki Kawasaki, Gregory M. Springett, Shinichiro Toki, Juan J. Canales, Patricia Harlan, Justin P. Blumenstiel, Emy J. Chen, I. Amy Bany, Naoki Mochizuki, Amy Ashbacher, Michiyuki Matsuda, David E. Housman, and Ann M. Graybiel, which appeared in number 22, October 27, 1998, of Proc. Natl. Acad. Sci. USA (95,(13278)(13279)(13280)(13281)(13282)(13283), due to a printer's error, the gene CalDAG-GEFII was referred to incorrectly in three places: in the heading of the second paragraph of Materials and Methods, in the first line of the Abbreviations footnote, and in line 11 of the second paragraph on page 13282. 318Corrections Proc. Natl. Acad. Sci. USA 96 (1999) Contributed by Ann M. Graybiel, August 20, 1998 ABSTRACT Ras proteins, key regulators of growth, differentiation, and malignant transformation, recently have been implicated in synaptic function and region-specific learning and memory functions in the brain. Rap proteins, members of the Ras small G protein superfamily, can inhibit Ras signaling through the Ras͞Raf-1͞mitogen-activated protein (MAP) kinase pathway or, through B-Raf, can activate MAP kinase. Rap and Ras proteins both can be activated through guanine nucleotide exchange factors (GEFs). Many Ras GEFs, but to date only one Rap GEF, have been identified. We now report the cloning of a brain-enriched gene, CalDAG-GEFI, which has substrate specificity for Rap1A, dual binding domains for calcium (Ca 2؉ ) and diacylglycerol (DAG), and enriched expression in brain basal ganglia pathways and their axon-terminal regions. Expression of CalDAG-GEFI activates Rap1A and inhibits Ras-dependent activation of the Erk͞MAP kinase cascade in 293T cells. Ca 2؉ ionophore and phorbol ester strongly and additively enhance this Rap1A activation. By contrast, CalDAG-GEFII, a second CalDAG-GEF family member that we cloned and found identical to

Background: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia.

The spontaneous behavior of humans can be altered dramatically by repeated exposure to psychomotor stimulants. We have developed a primate model for analyzing the neurobiology underlying such drug-induced behavioral changes. We performed ethogram-based behavioral assays on squirrel monkeys given single or multiple cocaine treatments, and in the same monkeys made anatomical plots of striatal neurons that were activated to express early-gene proteins. A final cocaine challenge after chronic intermittent exposure to cocaine induced highly patterned behavioral changes in the monkeys, affecting individual behavioral motifs in distinct ways. In the striatum, the challenge dose induced striosome-predominant expression combined with intense dorsal early-gene expression, especially in the putamen. These patterns of gene expression were highly predictive of the levels of stereotypy exhibited by the monkeys in response to cocaine challenge. The total levels of expression, on the other hand, appeared to reflect increased spontaneous behavioral activation during the drug-free period after the cocaine exposure. We suggest that in the primate, compartmentally and regionally specific striatal activation patterns contribute to the striatal modulation of psychostimulant-induced behaviors. These observations in nonhuman primates raise the possibility that monitoring such basal ganglia activity patterns could help to delineate the neural mechanisms underlying drug-induced repetitive behaviors and related syndromes in which stereotypies are manifest.

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