Brief CommunicationDissociating Barrel Development and Lesion-InducedPlasticity in the Mouse Somatosensory CortexAlexandra Rebsam,1Isabelle Seif,2and Patricia Gaspar11Institut National de la Sante´ et de la Recherche Me´dicale U616, Universite´ Paris VI Hoˆpital Salpeˆtrie`re, 75651 Paris cedex 13, France, and2Faculte´dePharmacie, Universite´ de Paris-Sud, 92296 Cha៮ tenay-Malabry, FranceIn the mouse somatosensory cortex, thalamocortical axons (TCAs) corresponding to individual whiskers cluster into restricted barreldomains during the first days of life. If whiskers are lesioned before that time, the cortical space devoted to the afferents from the damagedwhisker shrinks and becomes occupied by thalamocortical afferents from neighboring unlesioned whiskers. This plasticity ends bypostnatal day 3 (P3) to P4 when barrels emerge. To test whether TCA development and lesion-induced plasticity are linked, we usedmonoamine oxidase A knock-out (MAOA-KO) mice in which normal TCA development is halted by an excess of serotonin. Normal TCAdevelopment can be restored when serotonin levels are lowered by parachlorophenylalanine (PCPA). By varying the time of PCPAadministration, we found that barrel development can be reinitiated until P11, although the emergence of TCA clusters becomes gradu-ally slower and less complete. In mice in which barrels emerge 3 d later than the normal schedule, at P6 instead of P3, we examinedlesion-induced plasticity. We find a progressive decline of the lesion-induced plasticity and a closure at P3, similar to normal mice,showing that this plasticity is not influenced by an excess of serotonin levels. Thus, in MAOA-KO mice, theemergence of barrel patterningcan be delayed without a concomitant delay in lesion-induced plasticity, and the cortical space devoted to one whisker representationcannot be modified by the periphery once patterning is imprinted in the subcortical relays. We conclude that the closure of the lesion-induced plasticity period in the barrelfield is probably not determined at the cortical level.Key words: lesion; whisker; serotonin; barrelfield; thalamocortical; monoamine oxidase AIntroductionThe somatosensory cortex of rodents is a useful model for ana-lyzing the influence of sensory periphery and neural activity onpattern formation. In the cerebral cortex, each barrel corre-sponds to one whisker on the contralateral snout (Woolsey andVan der Loos, 1970). A barrel is formed by a bouquet of thalamo-cortical axon (TCA) terminals (Killackey and Leshin, 1975)around which layer IV stellate neurons aggregate (Woolsey et al.,1975). The clustering of TCAs into whisker-related patternsemerges during the first 3 postnatal days from an initially diffusedistribution in layer IV (Senft and Woolsey, 1991; Rebsam et al.,2002). During this period, the somatosensory map is plastic tochanges induced by peripheral lesions (Van der Loos and Wool-sey, 1973): lesioning a whisker row causes a reduction in therepresentation of this deprived row, whereas the representationof the adjacent rows expands. This effect diminishes with age, andno effect is visible when lesions are effected at postnatal day 4(P4), at a time when thalamocortical fibers are clearly segregatedinto barrel domains (Woolsey and Wann, 1976; Belford and Kil-lackey, 1980; Jeanmonod et al., 1981). Thus, the maturation ofthe barrelfield and its plasticity are concomitant, suggesting thatthe two processes are linked (Woolsey and Wann, 1976). To testthis hypothesis, a number of authors have tried to uncouple thesephenomena (Vongdokmai, 1980; Osterheld-Haas et al., 1994).However, these results can be questioned because the delay inbarrel emergence was limited and the experimental paradigmsthat were used implied a general delay of brain maturation. Totest whether these developmental events are linked, we chose amodel that allowed to delay the formation of barrels withoutaffecting the general brain maturation. We used the monoamineoxidase A knock-out (MAOA-KO) mouse, in which barrels arelacking in the cerebral cortex despite a normal patterning of thesubcortical sensory relays. The altered segregation of thalamo-cortical axons is attributable to an excess buildup of serotonin(5-HT) in the brain (Cases et al., 1996). The MAOA-KO mice canbe made to develop a normal barrelfield when the 5-HT1Brecep-tors are genetically invalidated (Salichon et al., 2001; Rebsam etal., 2002) or when 5-HT levels are reduced by daily injections ofparachlorophenylalanine (PCPA) from birth to P6 (Cases et al.,1996). PCPA is an inhibitor of tryptophan hydroxylase that sig-nificantly lowers 5-HT levels after 24 –48 h. We delayed the ad-ministration of PCPA to determine until when barrels can beinduced to form in the MAOA-KO mice and found that this canoccur until P10. Then, using mice witha3ddelay in barrelemergence, we analyzed the effects of peripheral lesions on barreldevelopment.Received Oct. 8, 2004; revised Nov. 24, 2004; accepted Nov. 29, 2004.This work was supported by Institut National de la Sante´ et de la Recherche Me´dicale, Centre National de laRecherche Scientifique, andFondationdeFrance.A.R. is funded by a grant from Fondation France Te´le´com Me´ce´natAutisme. We thank Nicole Ropert, Aude Muzerelle, and Constantino Sotelo for their help.Correspondence shouldbeaddressedto Patricia Gaspar, Institut National delaSante´ et de la Recherche Me´dicaleU616, Pavillon Enfant et Adolescent, Centre Hospitalier Universitaire Pitie´-Salpeˆtrie`re, 47 Boulevard de l’Hopital,75013 Paris, France. E-mail: [email protected]:10.1523/JNEUROSCI.4191-04.2005Copyright © 2005 Society for Neuroscience 0270-6474/05/250706-05$15.00/0706 • The Journal of Neuroscience, January 19, 2005 • 25(3):706 –710Materials and MethodsAnimals. Wild-type mice of the C3H/HeOuJ strain were purchased froma commercial source (Iffa Credo, Arbresle, France). The MAOA-KOmouse line has been described by Cases et al. (1995). Pregnant mice ofeach strain were examined twice daily to determine the moment of birth(noted as P0) with a 12 h precision.All of the experimental procedures were performed in accordance withthe provision for animal care and use of the European CommunityCouncil.PCPA treatment. P2–P21 pups were injected with PCPA (300 mg/kg,s.c., in saline) every 24 h for 1 week. The litter was separated from themother, and all of the pups received PCPA or saline and were returnedtogether to home cages.HPLC. Pups from MAOA-KO mice