Dynamic electrical synapses rewire brain networks for persistent oscillations and epileptogenesis

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• Mammalian telencephalic neural computation relies on sustained network activity beyond initial triggers.
• Persistent neural activity is fundamental for cognition but can cause disorders like epilepsy if dysregulated.
• Conventional models propose negative feedback loops between GABAergic interneurons (INs) and glutamatergic pyramidal neurons (PNs) to regulate activity.

Purpose of the Study:

• To investigate the drive behind self-perpetuating telencephalic activities.
• To characterize the role of electrical synapses between INs and PNs in the amygdala.
• To understand how these connections influence network oscillations and plasticity.

Main Methods:

• Investigated activity-dependent deployment of electrical synapses between INs and PNs in the amygdala.
• Analyzed the functional consequences of these direct synaptic links on neural computation.
• Examined the dynamic engagement and disengagement of electrical synapses based on neural activity levels.

Main Results:

• Discovered direct electrical synapses between INs and PNs in the amygdala.
• These synapses provide INs with dual excitatory and inhibitory actions on PNs, creating an intrinsic excitatory drive.
• This mechanism enables persistent network oscillations while preserving GABAergic negative feedback.
• Demonstrated that the functioning of these electrical synapses is dynamically regulated by neural activity, controlling network scale.
• Uncovered a wide-range, context-dependent plasticity in brain network wiring/rewiring.

Conclusions:

• Electrical synapses between INs and PNs are key to persistent telencephalic network oscillations and cognitive functions.
• The dynamic and activity-dependent nature of these synapses allows for flexible brain network organization.
• Dysregulation or pathological extension of this plasticity can contribute to epileptogenesis and other neuropsychiatric disorders.