Publication: TrkB receptor signaling and
activity-dependent inhibitory synaptogenesis
Authors
Seil, F.J.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
When mouse organotypic cerebellar cultures
were exposed to anti-GABA agents that increased
neuronal activity early in development, there was a
doubling of the ratio of inhibitory axosomatic synapse
profiles to Purkinje cell somatic profiles after two weeks
in vitro, which correlated with a decrease in spontaneous
cortical discharges. When similar cultures were
maintained in medium with activity blocking agents,
Purkinje cell axosomatic synapses were reduced to
approximately half of control values and, after recovery
from activity blockade, the cultures discharged
hyperactively. By contrast, the full complement of
excitatory cortical synapses developed in the absence of
neuronal activity. These results support the concept that
neuronal activity is necessary for the complete
development of inhibitory circuitry. When cerebellar
cultures were simultaneously exposed to activity
blocking agents and to neurotrophins BDNF or NT-4,
both of which bound to the TrkB receptor, the numbers
of inhibitory Purkinje cell axosomatic synapses were
similar to those of untreated control cultures, and control
rates of spontaneous cortical discharges were recorded.
The TrkC receptor ligand, NT-3, did not promote
inhibitory synapse development in the absence of
neuronal activity, and such cultures exhibited
hyperactive cortical discharges. These results are
consistent with a role for TrkB receptor ligands in
activity-dependent inhibitory synaptogenesis.
Subsequent exposure of cerebellar cultures to antibody
to the extracellular domain of TrkB induced an increased
development of Purkinje cell axosomatic synapses,
while similar antibody activation of TrkC had no effect
on inhibitory synaptogenesis. The promotion of
inhibitory synapse development by specific antibody
activation of TrkB supports the concept that signaling
for activity-dependent inhibitory synaptogenesis is via
the TrkB receptor.
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