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Summary: The locus coeruleus (LC) and noradrenergic neurotransmission are involved in the regulation of sudden unexpected death in epilepsy (SUDEP). Here, we present a protocol for modulating the noradrenergic pathway from LC to heart to prevent SUDEP in acoustic and pentylenetetrazole-induced DBA/1 mouse models of SUDEP. We describe steps for constructing SUDEP models, calcium signal recording, and electrocardiogram monitoring. We then detail measurement of tyrosine hydroxylase content and activity, β1 and p-β1-AR content, and destruction of LCNE neurons.For complete details on the use and execution of this protocol, please refer to Lian et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.