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Free keywords:
ACTIVITY-DEPENDENT REGULATION; CRITICAL PERIOD PLASTICITY; TERM SYNAPTIC
PLASTICITY; INHIBITORY SYNAPSES; VISUAL-CORTEX; DENDRITIC SPINES;
EXCITATORY SYNAPSES; HIPPOCAMPAL-NEURONS; NEUROTROPHIC FACTOR;
PRESYNAPTIC TERMINALSactivity-dependent plasticity; bouton dynamics; hippocampal organotypic
cultures; inhibitory axons; two-photon microscopy;
Abstract:
Coordinated changes at excitatory and inhibitory synapses are essential for normal brain development and function. It is well established that excitatory neurons undergo structural changes, but our knowledge about inhibitory structural plasticity is rather scarce. Here we present a quantitative analysis of the dynamics of GABAergic boutons in the dendritic region of the hippocampal CA1 area using time-lapse two-photon imaging in organotypic hippocampal cultures from GAD65-GFP mice. We show that similar to 20% of inhibitory boutons are not stable. They are appearing, disappearing and reappearing at specific locations along the inhibitory axon and reflect immature or incomplete synapses. Furthermore, we observed that persistent boutons show large volume fluctuations over several hours, suggesting that presynaptic content of inhibitory synapses is not constant. Our data show that inhibitory boutons are highly dynamic structures and suggest that inhibitory axons are continuously probing potential locations for inhibitory synapse formation by redistributing presynaptic material along the axon. In addition, we found that neuronal activity affects the exploratory dynamics of inhibitory axons. Blocking network activity rapidly reduces the number of transient boutons, whereas enhancing activity reduces the number of persistent inhibitory boutons, possibly reflecting enhanced competition between boutons along the axon. The latter effect requires signaling through GABA(A) receptors. We propose that activity-dependent regulation of bouton dynamics contributes to inhibitory synaptic plasticity.
