EXPRESSION OF c-Fos, Fos B, Jun B, AND Zif268 TRANSCRIPTION FACTOR PROTEINS IN RAT BARREL CORTEX FOLLOWING APOMORPHINE-EVOKED WHISKING BEHAVIOR R. K. FILIPKOWSKI, a;b * M. RYDZ a;c and L. KACZMAREK a a Department of Molecular and Cellular Neurobiology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland b Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA c Division of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, S-141 86 Huddinge, Sweden AbstractöApomorphine-evoked expression of transcription factor proteins: c-Fos, Fos B, Jun B, and Zif268 (also named Krox-24, NGFI-A, Egr-1), was investigated in rat somatosensory (barrel) cortex. The e¡ect of the N-methyl-D-aspartate receptor antagonist MK-801 on their expression was also analyzed. Apomorphine is a dopamine receptor agonist, eliciting motor activity, including enhanced whisking leading to the activation of vibrissae representation in the barrel cortex. Rats had their whiskers clipped on one side of the snout. The Zif268 levels were markedly reduced by this procedure alone. In contrast, apomorphine (5.0 mg/kg) evoked marked c-Fos elevation, less pronounced changes in Jun B and Zif268 and no change in Fos B. The greatest apomorphine-evoked c-Fos accumulation was observed in layers IV and V/VI of non-deprived barrel cortex and was not signi¢cantly in£uenced by MK-801 injection at 0.1 mg/kg. A higher dose of MK-801 (1.0 mg/kg) produced abnormalities in locomotor behavior and diminished c-Fos levels on the non-deprived side to the ones observed in the sensory stimulus-deprived cortex. We conclude that the response of the somatosensory cortex is selective with respect to both the gene activated and its cortical layer localization. Furthermore, sensory stimulation provides a major but not the only component to apomor- phine-evoked barrel cortex gene activation. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. Key words: vibrissae, NMDA receptor, immediate early genes, AP-1, MK-801. In the rodent vibrissae-barrel cortex system, sensory input produced by de£ection of the whiskers is conveyed via the brainstem and thalamus to cortical layer IV, where each cortical column, extending through all layers, contains a barrel, a discrete cluster of closely packed cells. There is one-to-one correspondence between each barrel and each vibrissa. The whisker-to-barrel system is contralateral, so the somatosensory cortex on one side represents vibrissae on the other side of the snout (Kossut, 1992). The part of the barrel ¢eld containing the large barrels and representing the vibrissae of the mystacial pad is called the postero-medial barrel sub¢eld (PMBSF) (Woolsey and Van der Loos, 1970), also known as the MV area (Chapin and Lin, 1984). Because of its simplicity, laterality as well as ethological and behavioral importance, the rodent somatosensory cortex, representing mystacial vibrissae (large whiskers) of the snout, o¡ers a very convenient system to study the e¡ects of sensory stimulation upon cortical function. Sensory stimulation plays an important role in neuronal plasticity (Buonomano and Merzenich, 1998) and recent studies indicate that gene expression may be of pivotal impor- tance for this phenomenon (Kaczmarek, 1993; Kaczmarek and Chaudhuri, 1997). The barrel cortex has already been a subject of inves- tigation of stimulation-evoked gene expression (see review by Filipkowski, 2000). In particular, Steiner and Gerfen (1994) as well as LaHoste et al. (1996) reported that the treatment of rats with dopamine agonists, such as apomorphine, known to enhance motor (including whisking) activity (Beck et al., 1986; Berke et al., 1998; Szechtman et al., 1982; Young et al., 1991), resulted in the accumulation of immediate early genes, c-fos and zif268 mRNA as well as c-Fos protein in var- ious brain regions including somatosensory cortex. This e¡ect was fully input-speci¢c, since clipping of the whiskers prevented the mRNA increase in the corre- sponding PMBSF (Steiner and Gerfen, 1994). Thus, it can be inferred that sensory input is critical for regulat- ing c-fos and zif268 expression in the barrel cortex. Fur- 679 *Correspondence to : R.K. Filipkowski, Cold Spring Harbor Labo- ratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. Tel.: +1-516-367-8886; fax: +1-516-367-8880. E-mail address : ¢lip@cshl.org (R. K. Filipkowski). Abbreviations : AP-1, activator protein-1 transcription factor ; apo, mice treated with apomorphine; apoMK, mice treated with apo- morphine and MK-801 (0.1 mg/kg); apoMK1, mice treated with apomorphine and MK-801 (1.0 mg/kg) ; CREB, cAMP-response element-binding protein transcription factor ; DAB, 3,3P-diamino- benzidine; FL/HL, forelimb/hindlimb, a part of the cortex receiv- ing sensory information from the limbs; MK, mice treated with MK-801 ; MK-801, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10-imine, dizocilpine ; NMDA, N-methyl-D-aspar- tate ; PBS, phosphate-bu¡ered saline ; PMBSF, postero-medial barrel sub¢eld. NSC 5151 18-10-01 www.neuroscience-ibro.com Neuroscience Vol. 106, No. 4, pp. 679^688, 2001 ß 2001 IBRO. Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved PII:S0306-4522(01)00310-4 0306-4522 / 01 $20.00+0.00