Traumatic Brain Injury Broadly Affects GABAergic Signaling in Dentate Gyrus Granule Cells.

Area of Science:

• Neuroscience
• Cellular and Molecular Biology
• Trauma Research

Background:

• Traumatic brain injury (TBI) is linked to neuropsychiatric disorders and epilepsy.
• GABAergic dysfunction is implicated in TBI pathophysiology, but its impact on hippocampal tonic inhibition is unclear.

Purpose of the Study:

• To investigate the effects of severe TBI on GABAergic signaling, specifically tonic inhibition, in dentate gyrus granule cells (DGGCs).

Main Methods:

• Utilized a controlled cortical impact (CCI) mouse model to assess GABAergic currents and receptor subunit expression in DGGCs.
• Measured tonic currents, spontaneous inhibitory postsynaptic currents (sIPSCs), and GABA_B receptor-mediated responses.

Main Results:

• CCI reduced THIP-induced tonic currents in ipsilateral DGGCs, indicating impaired δ subunit-containing GABA_A receptor function.
• Reduced frequency of sIPSCs and decreased expression of GABA_A receptor δ and GABA_B receptor B2 subunits were observed post-CCI.
• GABA_B receptor activation showed significantly attenuated tonic current potentiation and reduced K⁺ currents in ipsilateral DGGCs.

Conclusions:

• Severe TBI causes widespread GABAergic signaling disruption in DGGCs, affecting both phasic and tonic inhibition.
• Deficits in GABA_B receptor function contribute to the observed GABAergic dysfunction after TBI.
• These alterations are predicted to disrupt hippocampal network function and contribute to TBI sequelae like epilepsy.