Blast exposure triggers locus coeruleus hyperactivity, flooding the hippocampus with NE and elevating basal intracellular calcium levels in CA1 neurons. This causes heterogeneous reductions in fast Ca²⁺ transients tied to spiking activity and slow shifts in basal Ca²⁺, reducing network excitability without neuronal loss. Recovery occurs within ~1 hour, but repeated blasts sustain deficits in hippocampal-dependent tasks like novel object recognition.[pmc.ncbi.nlm.nih +3]

Synaptic and Molecular Impacts

Excess NE desensitizes α- and β-adrenergic receptors in CA1 and dentate gyrus, downregulating GluR1 phosphorylation at Ser845/Ser831 via PKA/CaMKII inhibition, weakening AMPA trafficking and LTP induction. Proteomic shifts include tau hyperphosphorylation and NLRP3 inflammasome activation, promoting microglial inflammation and progenitor proliferation deficits in dentate gyrus. Mossy fiber pathways show altered NMDA receptor contributions, shifting toward intermediate excitability between sham and moderate injury.[frontiersin +4]