Temporal Dynamics of Inhibitory Neurotransmission in the Adult Hippocampus After Hyperexcitability-Induced Damage

Inhibitory neurotransmission in the adult hippocampus is essential for regulating excitatory activity, synchronizing neuronal firing, and supporting cognitive function and emotional states. Brain damage such as traumatic brain injury (TBI) and ischemia disrupt this finely tuned inhibition, leading to excitation–inhibition imbalance further and pathological hyperexcitability. Here we review the populations of hippocampal inhibitory neurons, as well as the molecular and network-level alterations in inhibitory circuits following hippocampal damage. We detail how inhibitory neurotransmission progresses from acute synaptic dysfunction and interneuron vulnerability to chronic maladaptive remodeling and altered inhibitory signaling through time. These dynamic changes contribute to persistent network instability and cognitive deficits as well as emotional alterations. Understanding the temporal dynamics of inhibitory reorganization provides critical insights into mechanisms underlying post-injury hyperexcitability and identifies potential targets for therapeutic intervention aimed at restoring inhibitory control and hippocampal circuit function.