Anterior cingulate cortex neuron subtypes differentially regulate seizures

Area of Science:

• Neuroscience
• Epilepsy Research
• Cortical Circuitry

Background:

• The anterior cingulate cortex (ACC) plays a crucial role in regulating brain activity.
• Understanding neuronal subtypes within the ACC is vital for deciphering seizure modulation mechanisms.
• Acute seizures involve complex alterations in neuronal activity within critical brain regions.

Purpose of the Study:

• To investigate the regulatory roles of distinct neuronal subtypes in the ACC during acute seizures.
• To identify cell type-specific mechanisms underlying seizure modulation in the ACC.
• To elucidate the contribution of excitatory and inhibitory neurons to seizure dynamics.

Main Methods:

• Established acute seizure models in mice using pentylenetetrazol (PTZ) injection.
• Utilized in vivo fiber photometry, miniscope calcium imaging, and multichannel electroencephalography (EEG) to monitor neuronal activity and brain signals.
• Performed bidirectional chemogenetic and optogenetic manipulations on specific neuronal populations, including CaMKII excitatory neurons, vGAT-expressing GABAergic interneurons, and parvalbumin (PV) and somatostatin (SST) interneuron subpopulations.

Main Results:

• Both excitatory and inhibitory neurons in the ACC showed synchronized hyperactivity during seizures.
• Inhibition of CaMKII excitatory neurons reduced seizure severity, while their activation induced seizure-like activity.
• Activation of GABAergic interneurons decreased seizure frequency and severity; their inhibition worsened seizures.
• Somatostatin (SST) interneuron activation suppressed seizures, whereas parvalbumin (PV) interneuron activation did not show significant antiseizure effects.
• Inhibition of either PV or SST interneurons triggered spontaneous seizure-like activity, indicating their necessity for network stability.

Conclusions:

• Distinct ACC neuronal populations exhibit differential roles in acute seizure dynamics.
• Activating GABAergic interneurons or inhibiting CaMKII-positive neurons effectively suppresses seizure activity.
• SST interneurons contribute to seizure suppression, while PV interneurons are crucial for network stability.
• Both PV and SST interneurons play indispensable, complementary roles in maintaining cortical homeostasis and preventing epileptiform activity.
• Cortical stability relies on the excitation-inhibition balance and the cooperative interplay of multiple interneuron subtypes within the ACC.