Subcellular Structures in Native Hippocampal Synapses Revealed by Cryo-electron Tomography.

Area of Science:

• Neuroscience
• Cell Biology
• Structural Biology

Background:

• Synapses are crucial for brain function, requiring precise organization.
• Previous studies using cryo-electron tomography (cryo-ET) focused mainly on synaptic vesicles and receptors.
• Other critical synaptic components remain underexplored.

Purpose of the Study:

• To quantitatively analyze subcellular features of over 300 intact hippocampal synapses using cryo-ET.
• To provide a comprehensive view of synaptic structural organization.
• To suggest fundamental principles governing subcellular synaptic architecture.

Main Methods:

• Cryo-electron tomography (cryo-ET) was employed for nanoscale imaging.
• Quantitative analysis of over 300 intact hippocampal synapses.
• Identification and categorization of subcellular structures within synapses.

Main Results:

• 32% of excitatory synapses were on dendritic shafts; 35% of inhibitory synapses targeted dendritic spines.
• Four distinct synaptic cleft geometries were identified.
• Presynaptic boutons showed enrichment of dense core vesicles, dense granules, and clathrin cages.
• Mitochondria were abundant pre- and postsynaptically, with more matrix granules found postsynaptically.

Conclusions:

• Cryo-ET provides unprecedented detail on hippocampal synapse organization.
• Synaptic structure varies between excitatory and inhibitory synapses and their locations.
• Novel presynaptic structures and mitochondrial variations offer insights into synaptic function.