An endogenous adrenoceptor ligand potentiates excitatory synaptic transmission in cultured hippocampal neurons

Noradrenergic inputs modulate hippocampal function via distinct receptors. In hippocampal neuronal cultures, mRNA expression of adrenoceptor subtypes is maintained from 1 day in vitro (DIV) to 22 DIV. Noradrenaline dose-depen dently stimulates phosphoinositide (PI) breakdown in both immature and matu re cultures through the activation of al receptors. At 22 DIV, basal PI bre akdown depends on excitatory synaptic activity since it is decreased by tet rodotoxin or glutamate receptor antagonists. At 22 DIV, a similar decrease of basal PI breakdown is also observed with alpha1, alpha2 or beta adrenoce ptor antagonists. These effects are not additive with that produced by tetr odotoxin. Adrenergic antagonists also strongly reduce spontaneous excitator y post-synaptic currents (sEPSC) as evidenced by whole call recording. Ther efore, in hippocampal cultures, excitatory transmission is modulated by a t onic activation of adrenoceptors probably produced by an endogenous ligand. Indeed, (i) the depletion of catecholamine pools by reserpine also decreas es both basal PI metabolism and sEPSC; (ii) hippocampal neurons possess bot h tyrosine hydroxylase (TH) and dopamine-beta -hydroxylase mRNAs, encoding enzymes required for catecholamine synthesis; and (iii) some hippocampal ne urons show TH-immunoreactivity. TH-positive cells are also detected in E18 hippocampal sections. Thus, cultured hippocampal neurons synthesize and rel ease an adrenergic-like ligand, which tonically potentiates excitatory syna ptic transmission in mature cultures.