Modification of the synaptic cleft under excitatory conditions

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Plasticity

Background:

• The synaptic cleft, crucial for neuronal communication, is increasingly recognized for its role in synaptic efficacy.
• Its precise geometry and molecular organization significantly influence synaptic function.

Purpose of the Study:

• To investigate short-term morphological changes in the synaptic cleft under excitatory conditions using electron microscopy.
• To understand how synaptic cleft structure is affected by neuronal activity and chemical modulators.

Main Methods:

• Utilized electron microscopy to examine synaptic structures in cultured hippocampal neurons and adult brain tissue.
• Applied high potassium (K+) concentrations, tetrodotoxin (TTX), NMDA, APV, and EGTA to manipulate neuronal activity and calcium levels.

Main Results:

• High K+ depolarization and NMDA application significantly increased the frequency of peripherally widened synaptic clefts ('open clefts').
• TTX application, inhibiting basal activity, led to the disappearance of open clefts.
• Extracellular calcium depletion using EGTA also increased open cleft frequency, suggesting the role of Ca2+-dependent trans-synaptic bridges.

Conclusions:

• Excitatory conditions and calcium depletion promote synaptic cleft widening, likely by dissociating trans-synaptic bridges.
• This structural plasticity may allow mobile elements like AMPA receptors into the cleft.
• Peripheral cleft opening could enhance neurotransmitter clearance, potentially acting as a homeostatic or protective mechanism.