Biology Reference
In-Depth Information
neurons that typically have filopodia-like projections. A target or targets of
mir-125b regulating spine morphology are still unknown.
mir-134 is, like mir-124, a nervous system-specific miRNA. However,
unlike mir-124 that is expressed earlier, mir-134 expression in the hippo-
campus peaks around postnatal day 13 correlating with the time of synaptic
maturation (
Schratt
et al
., 2006
). mir-134 localizes to dendrites, where it
regulates spine morphology. First, in hippocampal neurons in culture, mir-
134 overexpression resulted in decreased dendritic spine volume, without
affecting the number of spines, through the repression of Lim-domain-
containing protein kinase 1 (
Limk1
)(
Schratt
et al
., 2006
). LIMK1 has been
shown to regulate dendritic spine morphology by affecting dynamics of the
actin cytoskeleton. However, upon neuronal activation—which is known
to stimulate dendritic growth—the inhibition on
Limk1
is relieved. Surpris-
ingly, in younger neurons, neuronal activity induces mir-134 expression
and through downregulation of Pumilio 2, mir-134 promotes dendritic
outgrowth (
Fiore
et al
., 2009
;
Khudayberdiev
et al
., 2009
). These seemingly
opposite roles of mir-134 can be reconciled in two different ways. First, it is
possible that mir-134 plays different roles at different time points, mediated
through distinct targets. Alternatively, both effects could be part of homeo-
stasis or plasticity mechanisms to coordinate global and local responses of a
neuron to increased or decreased neuronal activity. For example, an
increase in dendritic arborization has been shown to be accompanied by a
decrease in the strength of individual synapses to maintain the overall
excitability within a certain range (
Peng
et al
., 2009
). In addition, localized
effects of mir-134 in the synapse allow for differential downscaling or
strengthening of individual spines. Whether all three, mir-132, mir-134,
and mir-125b, act in the same cell to provide a coordinated, balanced
response or whether they act at different times and/or different cell types
need to be further explored to obtain a more comprehensive picture of their
function during dendritic formation and plasticity.
In addition, three different miRNAs have been shown to affect synaptic
strength and plasticity in three different organisms. In
Aplysia californica
, mir-
124 is, as in
C. elegans
, restricted to sensory neurons. The sensory-motor
synapse of
Aplysia
has been extensively studied, and it can be modulated by
serotonin. Serotonin is known to promote long-term facilitation at this
synapse through the activation of CREB. While mir-124 seems to target
CREB in the sensory neuron, interestingly, serotonin was found to inhibit
mir-124 biogenesis and thus relieve the repression this miRNA imposes on
CREB (
Rajasethupathy
et al
., 2009
). This arrangement forms a coherent
feedforward loop (FFL), postulated to increase the specificity of
the
response.
The other two cases involve miRNAs regulating the strength of the
neuromuscular junction (NMJ). The first report was from Kim and collea-
gues who showed that in
C. elegans
,
mir-1
, a conserved muscle-specific
