Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control

Area of Science:

• Neuroscience
• Epileptology
• Traumatic Brain Injury Research

Background:

• Traumatic brain injury (TBI) is a significant risk factor for developing pharmacoresistant epilepsy.
• The exact mechanisms linking TBI to epileptiform network activity remain unclear, despite known disruptions in brain circuitry.

Purpose of the Study:

• To investigate alterations in cortical excitability and glutamatergic signaling following controlled cortical impact (CCI) in a TBI model.
• To elucidate the role of specific neuronal microcircuits in initiating and spreading epileptiform activity post-TBI.

Main Methods:

• Utilized controlled cortical impact (CCI) to model TBI in acute brain slices.
• Employed FRET-based glutamate biosensors for optical mapping of cortical glutamate signaling.
• Simultaneously recorded cortical field potentials and analyzed synaptic currents (IPSCs and EPSCs).

Main Results:

• CCI induced epileptiform field potentials and altered input-output relationships in deep cortical layers.
• Significantly increased cortical glutamate signaling correlated with epileptiform activity.
• Decreased GABAergic interneuron markers and reduced inhibitory/increased excitatory synaptic currents were observed post-CCI.

Conclusions:

• Increased glutamatergic signaling, potentially due to diminished GABAergic control, offers a mechanism for TBI-induced post-traumatic epilepsy.
• Specific cortical neuronal microcircuits may initiate and propagate epileptiform activity following TBI.