An Endogenous Adrenoceptor Ligand Potentiates Excitatory Synaptic Transmission in Cultured Hippocampal Neurons

Abstract

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-dependently stimulates phosphoinositide (PI) breakdown in both immature and mature cultures through the activation of alpha1 receptors. At 22 DIV, basal PI breakdown depends on excitatory synaptic activity since it is decreased by tetrodotoxin or glutamate receptor antagonists. At 22 DIV, a similar decrease of basal PI breakdown is also observed with alpha1, alpha2 or beta adrenoceptor antagonists. These effects are not additive with that produced by tetrodotoxin. Adrenergic antagonists also strongly reduce spontaneous excitatory post-synaptic currents (sEPSC) as evidenced by whole cell recording. Therefore, in hippocampal cultures, excitatory transmission is modulated by a tonic activation of adrenoceptors probably produced by an endogenous ligand. Indeed, (i) the depletion of catecholamine pools by reserpine also decreases both basal PI metabolism and sEPSC; (ii) hippocampal neurons possess both tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase mRNAs, encoding enzymes required for catecholamine synthesis; and (iii) some hippocampal neurons show TH-immunoreactivity. TH-positive cells are also detected in E18 hippocampal sections. Thus, cultured hippocampal neurons synthesize and release an adrenergic-like ligand, which tonically potentiates excitatory synaptic transmission in mature cultures.

Pharmacological and neurochemical characterization of the involvement of hippocampal adrenoreceptor subtypes in the modulation of acute limbic seizures

“…2). The data are in line with the finding that α 1 ‐antagonism inhibits spontaneous excitatory synaptic activity in cultured hippocampal neurons (Aubert et al. 2001) but contrasts to previous in vitro investigations showing α 1 ‐adrenoreceptors to pre‐synaptically inhibit Glu release in the CA3 hippocampal area (Scanziani et al.…”

Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells

“…In contrast, experiments made on neurons of layer V of the medial prefrontal cortex and in mature cultured hippocampal neurons showed that activation of α1-ARs increase the frequency but not the amplitude of sEPSC. No differences were found on mEPSC (Marek and Aghajanian, 1999, Aubert et al, 2001). In accordance with the latter data, our results showed that enhancement of EPSCs by α1-AR activation is dependent on presynaptic action potentials given that the increased frequency was not observed in the presence of TTX, an established inhibitor of voltage-gated sodium channels (Narahashi et al, 1967).…”

“…The effects of α1-AR stimulation on spontaneous synaptic transmission have been previously assessed with contradictory results in cultured rat hippocampal neurons, and in brain slices of hypothalamus and cerebral cortex (Marek and Aghajanian, 1999, Aubert et al, 2001, Gordon and Bains, 2003, Dong et al, 2005, Gordon and Bains, 2005). Investigations on different nuclei of the hypothalamus and prelimbic cortex preparations have demonstrated that α1-AR activation increase mEPSC frequency.…”

L‐phenylalanine selectively depresses currents at glutamatergic excitatory synapses

“…L-Phe is the direct precursor of tyrosine, which in turn is metabolized to dopamine and norepinephrine. Although in the adult hippocampus norepinephrine is released mainly by fibers originating from the locus coeruleus (Loy et al, 1980), Aubert et al (2001) showed that cultured hippocampal neurons possess both tyrosine hydroxylase (TH) and dopamine-␤-hydroxylase mRNAs, and some hippocampal neurons show TH immunoreactivity. In addition, the presence of TH immunoreactivity has been reported in hippocampal cells under specific conditions, including colchicine-treated rats during development (Siddiqui et al, 1995) and following complex partial seizures in humans (Zhu et al, 1990).…”