The vertebrate spleen generally receives a discrete supply of nerve fibres of spinal autonomic (“sympathetic”) origin. The innervation is chiefly adrenergic, although both neuropeptides (mammals) and acetylcholine (teleost fish) are found to be neurotransmitters. The autonomic nerves control splenic blood flow and also, by contracting the capsular and trabecular smooth muscle of the spleen, serve to release sequestered erythrocytes from their splenic stores.

The cholinergic component in the excitatory innervation of the cod spleen is not present in other vertebrate groups. A “cholinergic supersensitivity” is observed after treatment with 6-hydroxydopamine, and this effect has been interpreted in favour of a “primitive”, non-differentiated adrenergic/cholinergic neuron from which catecholamines and acetylcholine are released to act upon their respective postsynaptic receptors of the splenic smooth muscle.