EH3B 11. S. LeVay, M. P. Stryker, C. J. Shatz, J. Comp. Neu- rol. 179, 223 (1978); A. Antonini and M. P. Stryker, J. Neurosci. 13,3549(1993). 12. A. Kirkwood, S. M. Dudek, J. T. Gold, C. D. Aizen- man, M. F. Bear, Science 260, 1518 (1993); A. Kirk- wood and M. F. Bear, J. Neurosci. 14, 3404 (1994); A. Kirkwood, H.-K. Lee, M. F. Bear, Nature 375, 328 (1995). 13. U. Drager, J. Neurophysiol. 41, 28 (1978); M. Fagio- lini et al., Vision Res. 34, 709 (1994). J. A. Gordon and M. P. Stryker [J. Neurosci., in press] show that ocular dominance plasticity in mouse primary visual cortex is subject to the same conditions and occurs in the same way as in the cat, involving both intra- cortical and thalamocortical changes (1). 14. Recordings were obtained from layer ll/lll in the bin- ocular zone of 400-fxm-thick coronal slices of mouse primary visual cortex (C57/BL6; <6 weeks old) con- tinuously superfused with oxygenated (95% 0 2 , 5% C02) artificial cerebrospinal fluid (ACSF), containing (in millimolar) 119 NaCI, 2.5 KCI, 1.3 MgS04, 1.0 NaH2P04, 26.2 NaHC03, 2.5 CaCI2, and 11 glucose. Extracellular pipettes (1 M NaCI, 1-3 megohm) moni- tored stable, half-maximal baseline field potentials evoked from layer IV by a bipolar Pt-lr electrode deliv- ering 100-fxs pulses at 0.1 Hz. Five episodes of TBS were given at 10-s intervals to induce LTP before depotentiation was attempted with 900 pulses at 1 Hz. A single TBS consisted of 10 repetitions of four stimuli at 100 Hz delivered at 200-ms intervals {12). All experiments were terminated by bath application of 10 fxM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, Tocris, UK) and 50 fxM D-(-)-2-amino-5-phosphono- valeric acid (D-APV, Sigma) to determine the synaptic component of the field response. Similar results were obtained by measurements of synaptic slope or peak amplitude normalized to the baseline period before TBS, and renormalized to the 10 min preceding 1 -Hz stimulation to adjust for variable elapsed time post- TBS across experiments. Both LTP and depotentia- tion were prevented by the A/-methyl-D-aspartate re- ceptor antagonist APV, as also reported for LTD of naive synapses {12). R,S-a-MCPG or (+)-MCPG (Tocris) were dissolved in 100 mM NaOH at 50 mM, then diluted to 500 \xM in ACSF. 15. K. R. Stratton, P. F. Worley, J. M. Baraban, Eur. J. Pharmacol. 186, 357 (1990); S. Charpak, B. H. Gah- wiler, K. Q. Do, T. Knopfel, Nature 347, 765 (1990); R. W. Gereau and P. J. Conn, J. Neurophysiol. 74, 122 (1995); A. Baskys, Trends Neurosci. 15, 92 (1992). 16. In visual cortical slices prepared and maintained as de- scribed {14), /AHP currents were evoked by stepping the membrane potential of regular-spiking supragranular pyramidal cells [D. A. McCormickef al., J. Neurophysiol. 54, 782 (1985)] from - 5 0 to +40 mV for 100 ms in the whole-cell voltage-clamp mode (Axoclamp-2B). The pi- pette solution contained (in millimolar): 122.5 potassium gluconate, 17.5 KCI, 10 Hepes buffer, 0.2 EGTA, 8 NaCI, 2.0 Mg-adenosine 5'-triphosphate, and 0.3 Na3- guanosine 5'-triphosphate (3 to 8 megohm, pH 7.2, 290 to 300 mOsm). t-ACPD (Tocris) was dissolved in ACSF and bath applied. 17. In vivo experiments were done as described [H. O. Reiter, D. M. Waitzman, M. P. Stryker, Exp. Brain Res. 65,182 (1986)]. Infusion cannulae connected to osmotic minipumps (Alza model 2002) were implant- ed bilaterally into postnatal day 28 (P28) kitten striate cortex under sterile conditions. One eyelid was su- tured shut under brief halothane anesthesia on P30, and MD was verified for 5 days. R,S-a- or (+)-MCPG (25 to 50 mM in 100 mM NaOH), or vehicle (100 mM NaOH, pH 10) solution was delivered at a constant rate (0.5 fxl/hour) throughout the experiment. In some cases, MCPG solutions were first neutralized to physiological pH 7, which rendered the drug inac- tive on the in vitro /AHP assay {16). On P35, animals were prepared for acute single-unit recording by standard techniques in accordance with University of California, San Francisco, guidelines for animal care. In brief, kittens were anesthetized and main- tained with a combination of barbiturate infusion [pentobarbital sodium (Nembutal) 10 mg/kg intrave- nous] and N20:02 (2:1) ventilation. Extracellular unit recordings were obtained immediately in front and no further than 1.5 mm from each cannula with resin- coated tungsten microelectrodes (1 to 3 megohms) in vertical penetrations spaced evenly at 400-fxm intervals along the medial bank. Electrode tracks were reconstructed in Nissl-stained coronal sections to confirm sampling from all layers of visual cortex. Light bar stimuli were swept across the receptive field with a hand-held lamp to assign each cell to an ocular dominance group on the basis of Hubel and Wiesel's seven-point scale (1). Here, an ocular dom- inance of 7 represents complete dominance by the open eye. The contralateral bias index (CBI), a weighted average of the bias toward one eye or the other, was calculated for each treated hemisphere, separately and as a group, according to the formula: CBI = [{n1 - n7) + 2 Mn2 - n6) + Vs{n3 - n5) + N]/{2N), where N is the total number of cells and nx is the number within ocular dominance group x. 18. In each hemisphere, multibarreled iontophoretic pi- pettes were lowered into striate cortex just beyond the most distant penetration site used for determina- tion of ocular dominance (<2 mm from cannula). Activation thresholds for kainic acid and t-ACPD (both 20 mM in saline) were determined by gradually increasing iontophoretic ejection currents (WPI model 160) in 20-nA steps once every 60 s. Each round of iontophoresis was preceded by isolation of multiple units with visual stimulation and concluded by verifying the presence of the same visually driven cells. Additional iontophoretic penetrations amidst the single-unit sites and well beyond (>3 mm) con- firmed that all shifted cells lay within a region in which mGluRs were blocked. 19. K. Lingenhohl, H.-R. Olpe, N. Bendali, T. Knopfel, Neurosci. Res. 18, 229 (1993); P. M. B. Cahusac, Eur. J. Neurosci. 6, 1505 (1994); D. E. Jane et al., Neuropharmacology 32, 725 (1993). 20. A. Antoninf and M. P. 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Only presynaptic mGluR4 is not blocked by MCPG in vitro {24). 29. O. Manzoni, M. G. Weisskopf, R. A. Nicoll, Eur. J. Neurosci. 6,1050 (1994); P. Chinestra, L. Anikstejn, D. Diabira, Y. Ben-Ari, J. Neurophysiol. 70, 2684 (1993); A. Y. Hsia et al., Neuropharmacology 34, 1567(1995). 30. Z. A. Bortolotto, Z. I. Bashir, C. H. Davies, G. L. Collingridge, Nature 368, 740 (1994). 31. We thank S. Harris for assistance during the implant surgeries, and M. Fagiolini and R. A. Nicoll for critical comments on the manuscript. T.K.H. is a Howard Hughes Medical Institute Predoctoral Fellow. Sup- ported by grants to M.P.S. from the National Insti- tutes of Health (EY02874) and the Human Frontiers Science Program (RG69/93). 3 October 1995; accepted 30 January 1996 moving helix-distorting lesions from cellu- lar genomes. The general strategy appears to be similar in organisms ranging from Esch- erichia coli to humans. This process is com- plex and requires the participation of a number of different proteins (1). Its role in ameliorating the carcinogenic consequenc- es of DNA damage has been inferred from studies of the genetic disease xeroderma pigmentosum (XP). Cells from XP patients are hypersensitive to the killing and muta- genic effects of ultraviolet light (UV) and 557 Transcription-Coupled Repair Deficiency and Mutations in Human Mismatch Repair Genes Isabel Mellon,* Deepak K. Rajpal, Minoru Koi, C. Richard Boland, Gregory N. Champe Deficiencies in mismatch repair have been linked to a common cancer predisposition syndrome in humans, hereditary nonpolyposis colorectal cancer (HNPCC), and a subset of sporadic cancers. Here, several mismatch repair-deficient tumor cell lines and HNPCC-derived lymphoblastoid cell lines were found to be deficient in an additional DNA repair process termed transcription-coupled repair (TCR). The TCR defect was corrected in a mutant cell line whose mismatch repair deficiency had been corrected by chromo- some transfer. Thus, the connection between excision repair and mismatch repair pre- viously described in Escherichia coli extends to humans. These results imply that defi- ciencies in TCR and exposure to carcinogens present in the environment may contribute to the etiology of tumors associated with genetic defects in mismatch repair.