Propagating Activity in Neocortex, Mediated by Gap Junctions and Modulated by Extracellular Potassium

Area of Science:

• Neuroscience
• Computational Neuroscience
• Cellular Neuroscience

Background:

• Parvalbumin-expressing interneurons form gap junction-coupled networks.
• These networks support synchronized activity, but propagation in natural states is unclear.
• Extracellular potassium ([K+]o) increases during intense neural activity, like seizures.

Purpose of the Study:

• To investigate if parvalbumin-expressing interneuron activity propagates under elevated [K+]o.
• To determine the mechanisms underlying activity propagation.
• To compare propagation under elevated [K+]o with 4-aminopyridine-induced activity.

Main Methods:

• Optogenetic activation of parvalbumin-expressing interneurons in mouse visual cortex.
• Recording neural activity with a linear electrode array.
• Manipulating [K+]o and using pharmacological blockers (GABAergic, glutamatergic, gap junction inhibitors).
• Computational modeling of network dynamics.

Main Results:

• At baseline [K+]o, activity was confined to the activated area.
• Elevated [K+]o (>8.0 mm) enabled propagation of interneuron activity (59.1 mm/s).
• Propagation was independent of GABAergic transmission but modulated by glutamatergic blockers.
• Gap junction blockade (quinine, mefloquine, carbenoxolone) prevented propagation.

Conclusions:

• Elevated [K+]o facilitates gap junction-dependent propagation of parvalbumin-expressing interneuron activity.
• This syncytial propagation mechanism may influence seizure dynamics.
• Propagation differs qualitatively between high [K+]o and 4-aminopyridine conditions.