The Journal of Neuroscience, February 25, 2004 • 24(8):i • i This Week in The Journal F Cellular/Molecular length protein but was later found to pro- reward-directed behavior. Okay, but duce a spliced isoform lacking the external maybe the authors should have tried $20! cAMP and a Retinal Clock neurotrophin-binding site. More recently, a Chiaki Fukuhara, Cuimei Liu, Tamara mouse with a mutation in exon IV was N. Ivanova, Guy C.-K. Chan, Daniel R. thought to be entirely p75NTR deficient, Storm, P. Michael Iuvone, and Gianluca but it now appears that its high mortality and severe defects may result in part from an Tosini unexpected gain-of-function. Paul et al. (see pages 1803–1811) identified a 26 kDa protein in exon IV Ϫ/Ϫ In photoreceptors, an autonomous circa- mice that contains the transmembrane dian clock interacts with the light/dark cy- and intracellular domains of p75NTR. cle to control aspects of retinal function. Transcription of the fragment was driven The circadian pattern of melatonin syn- by a sequence within the inserted pGK-Neo thesis in photoreceptors is regulated by cassette in exon IV. Overexpression of the Blood oxygen level-dependent (BOLD) signals in subjects arylalkylamine N-acetyltransferase (AA- fragment activated p75NTR-mediated sig- whowereanticipatingrespondingformonetarygain.Signals NAT). Transcription of AA-NAT is under naling cascades leading to apoptosis. The intheventralstriatumwerebilaterallyenhancedinadults(B) Ϫ/Ϫ dual control by CLOCK and BMAL1 tran- exon IV mouse, although perhaps not compared with adolescents (A). scription factors at an E-box transcrip- the true null it was thought to be, may still tional site, and by a cAMP:cAMP response help reveal the complex signaling of ࡗ Neurobiology of Disease element (CRE)-mediated site. Fukuhara p75NTR. Friedreich Ataxia in the Mouse et al. now report that the gene for type 1 f adenylyl cyclase (AC1) also contains an Behavioral/Systems/Cognitive Delphine Simon, Herve´ Seznec, Anne E-box site, and it too is controlled by the Gansmuller, Nade`ge Carelle, Philipp CLOCK:BMAL1 complex. The clock Motivation, the Brain, and the Adolescent Weber, Daniel Metzger, Pierre Rustin, genes exerted rhythmic control of AC1 ex- Michel Koenig, and He´le`ne Puccio pression, and thus cAMP synthesis, in the James M. Bjork, Brian Knutson, Grace (see pages 1987–1995) retina as well as in the pineal gland and W. Fong, Daniel M. Caggiano, Shannon suprachiasmatic nucleus. Because AC1 is M. Bennett, and Daniel W. Hommer Friedreich’s ataxia (FRDA) is named for calcium dependent, the nighttime in- (see pages 1793–1802) the resulting progressive balance deficits crease in photoreceptor cytoplasmic cal- and sensory neuropathy, but it is also as- cium, induced by the depolarizing dark What motivates teenagers is a question sociated with diabetes and cardiomyopa- current, increases cAMP and thus melato- that can baffle parents and teachers. Phys- thy. The disease is most commonly caused nin synthesis. The authors suggest that ical differences in the motivational circuit by GAA triplet expansion in the first in- clock control of cAMP signaling may of the ventral striatum have been sug- tron of frataxin, leading to reduced tran- serve a general role in the integration of gested as underlying the tendency of some scription. Frataxin is a mitochondrial pro- circadian signals. teens to take risks without fully consider- tein that is involved in iron–sulfur Œ ing the consequences. Does risk-taking re- complex (ISC) assembly. Reduced func- Development/Plasticity/Repair sult from an “overactive” motivational tion of the ISC can cause oxidative stress p75: Lessons from a Knock-Out That circuitry or from a hypoactive circuit that and iron accumulation. Although the cel- requires high-risk/high-reward incen- lular effects have been studied in yeast, an Wasn’t a Knock-Out tives? In this week’s Journal, Bjork et al. animal model would facilitate studies of Christine E. Paul, Emily Vereker, compared teen and adult brain activity in disease mechanisms. Because frataxin- Kathleen M. Dickson, and Philip A. the ventral striatum during a money- deficient mice do not survive long enough Barker motivated game. In all subjects, anticipa- to allow detailed study, Simon et al. cre- (see pages 1917–1923) tion of monetary gain (20 cents, $1, or $5) ated two conditional, neuron-specific caused activation of the ventral striatum, knock-out mice. The mice have a normal The p75 neurotrophin receptor (p75NTR) whereas notification of gain activated the life expectancy, but they show ataxia and remains an enigma. It binds all neurotro- mesial frontal cortex. However, teens aged progressive sensory loss as in FRDA. The phins and can activate seemingly opposing 12–17 showed less activation in the right death of large sensory neurons in the dor- signaling cascades. Several transgenic nucleus accumbens in anticipation of sal root ganglia appeared to be autophagic mouse models have been created to ad- monetary gain than did young adults. The rather than apoptotic. These mice should dress the function of p75NTR in vivo.An authors suggest that adolescents show help unravel the pathophysiology of exon III Ϫ/Ϫ mouse expresses no full- reduced recruitment of motivational FRDA. The Journal of Neuroscience February 25, 2004 • Volume 24 Number 8 www.jneurosci.org i This Week in The Journal Brief Communications 1833 A Rapid and Precise On-Response in Posterior Parietal Cortex James W. Bisley, B. Suresh Krishna, and Michael E. Goldberg Œ 1917 A Pro-Apoptotic Fragment of the p75 Neurotrophin Receptor Is Expressed in p75NTRExonIV Null Mice Christine E. Paul, Emily Vereker, Kathleen M. Dickson, and Philip A. Barker 1936 Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Cover picture: Optical recording of synaptic NMDA Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice receptor activation in an acute hippocampal slice. CA1 Christian A. A. von Hehn, Arin Bhattacharjee, and Leonard K. Kaczmarek pyramidal cells (background image) are loaded with a mixture of calcium-sensitive (green) and calcium- 1962 Distinct Roles of Hippocampal De Novo Protein Synthesis and Actin Rearrangement in insensitive (red) dye. The stochastic responses of Extinction of Contextual Fear several synapses to extracellular stimulation of the Andre´ Fischer, Farahnaz Sananbenesi, Christina Schrick, Joachim Spiess, and presynaptic axons are revealed by the increase in Jelena Radulovic fluorescence intensity of the calcium-sensitive dye (yellow spines). Ten separate trials are shown in Articles separate frames. For details, see the article by CELLULAR/MOLECULAR Nimchinsky et al. in this issue (pages 2054–2064). ᭹ 1803 Gating of the cAMP Signaling Cascade and Melatonin Synthesis by the Circadian Clock in Mammalian Retina Chiaki Fukuhara, Cuimei Liu, Tamara N. Ivanova, Guy C.-K. Chan, Daniel R. Storm, P. Michael Iuvone, and Gianluca Tosini 1888 Clearance of ␣-Synuclein Oligomeric Intermediates via the Lysosomal Degradation Pathway He-Jin Lee, Farnaz Khoshaghideh, Smita Patel, and Seung-Jae Lee 1897 Reelin and Cyclin-Dependent Kinase 5-Dependent Signals Cooperate in Regulating Neuronal Migration and Synaptic Transmission Uwe Beffert, Edwin J. Weeber, Gerardo Morfini, Jane Ko, Scott T. Brady, Li-Huei Tsai, J. David Sweatt, and Joachim Herz 2004 Monitoring Clathrin-Mediated Endocytosis during Synaptic Activity Veronika J. Mueller, Martin Wienisch, Ralf B. Nehring, and Jurgen Klingauf 2054 The Number of Glutamate Receptors Opened by Synaptic Stimulation in Single Hippocampal Spines Esther A. Nimchinsky, Ryohei Yasuda, Thomas G. Oertner, and Karel Svoboda DEVELOPMENT/PLASTICITY/REPAIR 1812 Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABAA Receptor Subunits Angelica Zepeda, Frank Sengpiel, Miguel Angel Guagnelli, Luis Vaca, and Clorinda Arias 1852 Distinct Roles of Different Neural Cell Adhesion Molecule (NCAM) Isoforms in Synaptic Maturation Revealed by Analysis of NCAM 180 kDa Isoform-Deficient Mice Luis Polo-Parada, Christian M. Bose, Florian Plattner, and Lynn T. Landmesser 1873 Oxidized Galectin-1 Stimulates Macrophages to Promote Axonal Regeneration in Peripheral Nerves after Axotomy Hidenori Horie, Toshihiko Kadoya, Naoshi Hikawa, Kazunori Sango, Hiroko Inoue, Kaori Takeshita, Reiko Asawa, Tomoko Hiroi, Manami Sato, Tohru Yoshioka, and Yoshihiro Ishikawa 1941 Essential Function of Oncostatin M in Nociceptive Neurons of Dorsal Root Ganglia Yoshihiro Morikawa, Shinobu Tamura, Ken-ichi Minehata, Peter J. Donovan, Atsushi Miyajima, and Emiko Senba 1976 L1/Laminin Modulation of Growth Cone Response to EphB Triggers Growth Pauses and Regulates the Microtubule Destabilizing Protein SCG10 Leejee H. Suh, Stephen F. Oster, Sophia S. Soehrman, Gabriele Grenningloh, and David W. Sretavan 2027 DRAGON: A Member of the Repulsive Guidance Molecule-Related Family of Neuronal- and Muscle-Expressed Membrane Proteins Is Regulated by DRG11 and Has Neuronal Adhesive Properties Tarek A. Samad, Ashok Srinivasan, Laurie A. Karchewski, Sung-Jin Jeong, Jason A. Campagna, Ru-Rong Ji, David A. Fabrizio, Ying Zhang, Herbert Y. Lin, Esther Bell, and Clifford J. Woolf BEHAVIORAL/SYSTEMS/COGNITIVE f 1793 Incentive-Elicited Brain Activation in Adolescents: Similarities and Differences from Young Adults James M. Bjork, Brian Knutson, Grace W. Fong, Daniel M. Caggiano, Shannon M. Bennett, and Daniel W. Hommer 1822 Attention to Features Precedes