GABAergic input onto CA3 hippocampal interneurons remains shunting throughout development

Area of Science:

• Neuroscience
• Developmental Biology
• Cellular Electrophysiology

Background:

• Hippocampal excitability is regulated by inhibitory interneurons.
• GABAergic inhibition in principal cells shifts from depolarizing to hyperpolarizing during development.
• This shift is mediated by chloride cotransporters NKCC1 and KCC2.

Purpose of the Study:

• To investigate if inhibitory input onto hippocampal interneurons also undergoes a developmental shift in polarity.
• To explore the role of chloride cotransporters in regulating inhibitory input onto interneurons across development.

Main Methods:

• Gramicidin perforated-patch recordings from CA3 hippocampal stratum lucidum interneurons and pyramidal cells.
• Monitoring of GABA(A) receptor-mediated synaptic input and inhibitory postsynaptic potential (IPSC) reversal potential.
• Assessment of sensitivity to chloride cotransporter blockers (KCC2 and NKCC1).

Main Results:

• GABAergic input onto stratum lucidum interneurons remained shunting (depolarizing) across the entire developmental range (postnatal day 5-31).
• IPSC reversal potential and resting membrane potential were consistently close in interneurons.
• Sensitivity to KCC2 and NKCC1 blockers did not change with age, suggesting fixed cotransporter expression.

Conclusions:

• Unlike principal cells, inhibitory synaptic input onto CA3 interneurons exhibits a persistent shunting inhibition throughout development.
• The developmental switch in GABAergic inhibition polarity observed in principal cells does not occur in these interneurons.
• This suggests distinct developmental trajectories for inhibitory signaling in different hippocampal cell types.