Synapse elimination accompanies functional plasticity in hippocampal neurons

Area of Science:

• Neuroscience
• Developmental Biology
• Synaptic Plasticity

Background:

• Synapse elimination is crucial for nervous system development and relies on neuronal activity.
• Long-term potentiation (LTP) and long-term depression (LTD) modify synaptic strength, correlating with spine size changes.
• It remains unclear if LTD-induced spine shrinkage leads to synapse separation.

Purpose of the Study:

• To investigate whether long-term depression (LTD) can cause synapse elimination through the separation of synaptic structures.
• To visualize the dynamic process of synapse loss during LTD in live neuronal cultures.

Main Methods:

• Concurrent imaging and electrophysiological recording of live synapses in cultured rat hippocampal slices.
• Neuronal labeling with fluorescent proteins to visualize presynaptic (red) and postsynaptic (green) structures.
• Induction of LTD using low-frequency stimulation.

Main Results:

• LTD induction reduced colocalization of presynaptic and postsynaptic markers, indicating structural changes.
• Complete separation of presynaptic boutons from dendritic spines was observed in many cases.
• Synapse separation was linked to initial spine size and depression magnitude, not spine shrinkage during LTD.
• Spine loss did not accompany synapse separation during the observation period.

Conclusions:

• Repeated low-frequency stimulation during LTD induction can restructure synaptic contacts, leading to synapse elimination.
• This process provides insight into activity-dependent refinement of brain circuitry during development.
• The findings highlight a mechanism for synapse loss independent of spine shrinkage.