Excitatory Synaptic Input to Hilar Mossy Cells under Basal and Hyperexcitable Conditions

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Synaptic Plasticity

Background:

• Hilar mossy cells (HMCs) in the hippocampus are crucial for cognitive processing and epilepsy.
• Excitatory inputs to HMCs from dentate granule cells (via mossy fibers) and CA3 neurons are not fully understood.
• Understanding these synapses is key to deciphering hippocampal function and dysfunction.

Purpose of the Study:

• To compare synaptic properties of mossy fiber (MF) and CA3 inputs to HMCs.
• To investigate the roles of these inputs in hippocampal hyperexcitability models.
• To characterize age- and sex-dependent differences in these excitatory connections.

Main Methods:

• Electrophysiological recordings of excitatory postsynaptic currents (EPSCs) in HMCs.
• Comparison of pre- and postsynaptic parameters between MF-HMC and CA3-HMC synapses.
• Induction of hippocampal hyperexcitability using pharmacological agents and kainate injection models.

Main Results:

• MF-HMC synapses showed larger EPSC amplitudes, postsynaptic kainate receptors, and lower NMDA/AMPA ratios than CA3-HMC synapses.
• MF inputs exhibited less short-term plasticity (paired-pulse facilitation) compared to previously studied MF-CA3 synapses.
• Hippocampal hyperexcitability induced strong spontaneous bursts of compound EPSCs (cEPSCs) from CA3-HMC connections, particularly in young mice.

Conclusions:

• CA3-HMC synapses are dynamically regulated and can become powerful drivers of HMC excitation during hyperexcitability.
• This CA3-driven HMC activity may contribute to network hyperexcitability and seizure generation.
• The findings highlight distinct roles for MF and CA3 inputs in hippocampal circuit function and epilepsy.