Synaptic Signaling by All-Trans Retinoic Acid in Homeostatic Synaptic Plasticity

被引:304
作者
Aoto, Jason [1 ]
Nam, Christine I. [1 ]
Poon, Michael M. [1 ]
Ting, Pamela [1 ]
Chen, Lu [1 ,2 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
关键词
D O I
10.1016/j.neuron.2008.08.012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Normal brain function requires that the overall synaptic activity in neural circuits be kept constant. Longterm alterations of neural activity lead to homeostatic regulation of synaptic strength by a process known as synaptic scaling. The molecular mechanisms underlying synaptic scaling are largely unknown. Here, we report that all-trans retinoic acid (RA), a well-known developmental morphogen, unexpectedly mediates synaptic scaling in response to activity blockade. We show that activity blockade increases RA synthesis in neurons and that acute RA treatment enhances synaptic transmission. The RA-induced increase in synaptic strength is occluded by activity blockade-induced synaptic scaling. Suppression of RA synthesis prevents synaptic scaling. This form of RA signaling operates via a translation-dependent but transcription-independent mechanism, causes an upregulation of postsynaptic glutamate receptor levels, and requires RAR alpha receptors. Together, our data suggest that RA functions in homeostatic plasticity as a signaling molecule that increases synaptic strength by a protein synthesis-dependent mechanism.
引用
收藏
页码:308 / 320
页数:13
相关论文
共 59 条
[1]   Control of synaptic strength by glial TNFα [J].
Beattie, EC ;
Stellwagen, D ;
Morishita, W ;
Bresnahan, JC ;
Ha, BK ;
Von Zastrow, M ;
Beattie, MS ;
Malenka, RC .
SCIENCE, 2002, 295 (5563) :2282-2285
[2]   VITAMIN-A METABOLISM - NEW PERSPECTIVES ON ABSORPTION, TRANSPORT, AND STORAGE [J].
BLOMHOFF, R ;
GREEN, MH ;
GREEN, JB ;
BERG, T ;
NORUM, KR .
PHYSIOLOGICAL REVIEWS, 1991, 71 (04) :951-990
[3]   All-trans- retinoic acid stimulates translation and induces spine formation in hippocampal neurons through a membrane-associated RARα [J].
Chen, Na ;
Napoli, Joseph L. .
FASEB JOURNAL, 2008, 22 (01) :236-245
[4]   An essential role for retinoid receptors RARβ and RXRγ in long-term potentiation and depression [J].
Chiang, MY ;
Misner, D ;
Kempermann, G ;
Schikorski, T ;
Giguère, V ;
Sucov, HM ;
Gage, FH ;
Stevens, CF ;
Evans, RM .
NEURON, 1998, 21 (06) :1353-1361
[5]   Vitamin A deficiency produces spatial learning and memory impairment in rats [J].
Cocco, S ;
Diaz, G ;
Stancampiano, R ;
Diana, A ;
Carta, M ;
Curreli, R ;
Sarais, L ;
Fadda, F .
NEUROSCIENCE, 2002, 115 (02) :475-482
[6]   Homeostatic control of neural activity: From phenomenology to molecular design [J].
Davis, Graeme W. .
ANNUAL REVIEW OF NEUROSCIENCE, 2006, 29 :307-323
[7]   IDENTIFICATION OF A RETINOIC ACID RESPONSIVE ELEMENT IN THE RETINOIC ACID RECEPTOR-BETA GENE [J].
DETHE, H ;
VIVANCORUIZ, MD ;
TIOLLAIS, P ;
STUNNENBERG, H ;
DEJEAN, A .
NATURE, 1990, 343 (6254) :177-180
[8]   ADULT-RABBIT BRAIN SYNTHESIZES RETINOIC ACID [J].
DEV, S ;
ADLER, AJ ;
EDWARDS, RB .
BRAIN RESEARCH, 1993, 632 (1-2) :325-328
[9]   Retinoic acid inhibits expression of TNF-α and iNOS in activated rat microglia [J].
Dheen, ST ;
Jun, Y ;
Yan, Z ;
Ling, EA .
GLIA, 2005, 50 (01) :21-31
[10]   Citral, an inhibitor of retinoic acid synthesis, attenuates the frequency and severity of branchial arch abnormalities induced by triazole-derivative fluconazole in rat embryos cultured in vitro [J].
Di Renzo, Francesca ;
Broccia, Maria L. ;
Giavini, Errninio ;
Menegola, Elena .
REPRODUCTIVE TOXICOLOGY, 2007, 24 (3-4) :326-332