RT Journal Article
SR Electronic
T1 Telencephalin Slows Spine Maturation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1776
OP 1786
DO 10.1523/JNEUROSCI.2651-05.2006
VO 26
IS 6
A1 Hitomi Matsuno
A1 Shigeo Okabe
A1 Masayoshi Mishina
A1 Toshio Yanagida
A1 Kensaku Mori
A1 Yoshihiro Yoshihara
YR 2006
UL http://www.jneurosci.org/content/26/6/1776.abstract
AB Dendritic filopodia are highly dynamic structures, and morphological maturation from dendritic filopodia to spines is intimately associated with the stabilization and strengthening of synapses during development. Here, we report that telencephalin (TLCN), a cell adhesion molecule belonging to the Ig superfamily, is a negative regulator of spine maturation. Using cultured hippocampal neurons, we examined detailed localization and functions of TLCN in spine development and synaptogenesis. At early stages of synaptogenesis, TLCN immunoreactivity gradually increased and was present in dendritic shafts and filopodia. At later stages, TLCN tended to be excluded from mature spine synapses in which PSD-95 (postsynaptic density-95) clusters were apposed to presynaptic synaptophysin clusters. To elucidate the function of TLCN in spine maturation, we analyzed the dendrite morphology of TLCN-overexpressing and TLCN-deficient neurons. Overexpression of TLCN caused a dramatic increase in the density of dendritic filopodia and a concomitant decrease in the density of spines. Conversely, TLCN-deficient mice showed a decreased density of filopodia and an acceleration of spine maturation in vitro as well as in vivo. These results demonstrate that TLCN normally slows spine maturation by promoting the filopodia formation and negatively regulating the filopodia-to-spine transition. In addition, we found that spine heads of mature neurons were wider in TLCN-deficient mice compared with wild-type mice. Thus, the preservation of immature synapses by TLCN may be an essential step for refinement of functional neural circuits in the telencephalon, that take charge of higher brain functions such as learning, memory, and emotion.