Subthreshold Kir and Ih currents modulate excitability of layer 1 VIP interneurons in the medial prefrontal cortex
Claudio Moreno1, Denise Riquelme1, Camila Cornejo1
1Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
Biological Research
|February 14, 2026
Summary
Vasoactive intestinal peptide (VIP) interneurons in the medial prefrontal cortex (mPFC) use hyperpolarization-activated cation (Ih) and inward-rectifying potassium (Kir) currents to control neuronal excitability and information flow. These currents shape how VIP cells process signals in the mPFC.
Area of Science:
- Neuroscience
- Cellular Electrophysiology
- Computational Neuroscience
Background:
- Cortical layer 1 (L1) integrates sensory information and contains vasoactive intestinal peptide (VIP)-expressing interneurons.
- VIP interneurons regulate cortical circuits by disinhibiting pyramidal neurons, but their subthreshold ionic mechanisms are unclear.
- Understanding these mechanisms is crucial for deciphering information processing in the medial prefrontal cortex (mPFC).
Purpose of the Study:
- To characterize the electrophysiological properties of L1b VIP interneurons in the mouse mPFC.
- To investigate the roles of the hyperpolarization-activated cation current (Ih) and inward-rectifying potassium current (Kir) in shaping VIP interneuron excitability.
- To determine how these currents influence synaptic integration and information flow in the mPFC.
Main Methods:
- Whole-cell patch-clamp recordings in acute mouse mPFC slices.
- Pharmacological inhibition of Ih (ZD-7288) and Kir (BaCl2).
- Voltage-clamp recordings and immunofluorescence for HCN channel expression.
Main Results:
- L1b VIP interneurons exhibit constitutively active Ih and Kir currents near resting membrane potential.
- Inhibition of Ih or Kir individually altered resting membrane potential, input resistance, action potential duration, and firing frequency.
- Both currents enhanced EPSP-spike coupling probability, while neither affected spontaneous or miniature EPSC properties.
Conclusions:
- Ih and Kir currents are key regulators of L1b VIP interneuron passive properties and intrinsic excitability in the mPFC.
- These currents jointly control EPSP-spike coupling, influencing how VIP interneurons integrate synaptic inputs.
- The interplay between Ih and Kir shapes signal filtering and information flow within the prefrontal cortical column.
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