Looking After Polysialic Acid

Science's STKE  04 Dec 2007:
Vol. 2007, Issue 415, pp. tw437
DOI: 10.1126/stke.4152007tw437

Many aspects of brain function are modulated by neuronal activity; in some cases, the effects of activity are restricted to particular developmental stages, or critical periods. For instance, loss of visual input from one eye early in life leads to a shift in the responsiveness of neurons in the visual cortex toward the functional eye. The onset and time course of this critical period for ocular dominance plasticity is influenced by the maturation of GABAergic innervation, which is itself regulated by visual input and neuronal activity. But how? Di Cristo et al. found that polysialic acid [PSA, a homopolymer of sialic acid that attaches to neural cell adhesion molecules (NCAMs) and modulates intercellular bonds] and NCAMs were abundant in the neonatal mouse visual cortex but that PSA underwent a steep decline after eye opening. Pups reared in the dark showed increased PSA compared with pups reared under conventional light/dark cycles, and pharmacological suppression of visual signals suppressed the decline. In organotypic cortical cultures, enzymatic removal of PSA with endoneuramidase led to premature maturation of the innervation of pyramidal cell somata by GABAergic basket interneurons. Similarly, endoneuramidase injection into the visual cortex promoted both perisomatic GABAergic innervation and the frequency of miniature inhibitory postsynaptic currents. Moreover, it stimulated the early onset of the critical period for ocular dominance plasticity. Thus, the authors conclude that maturation of GABAergic inhibition--and thereby the initiation of ocular dominance plasticity--is regulated by an activity-dependent decrease in PSA.

G. Di Cristo, B. Chattopadhyaya, S. J. Kuhlman, Y. Fu, M.-C. BĂ©langer, C. Z. Wu, U. Rutishauser, L. Maffei, Z. J. Huang, Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity. Nat. Neurosci. 10, 1569-1577 (2007). [PubMed]