Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic neurones

Abstract

AbstractöDopamine-containing neurones of the ventral tegmental area express neurotensin receptors which are involved in regulating cell ¢ring and dopamine release. Although indirect evidence suggests that some neurotensin receptors may be localised on the nerve terminals of dopaminergic neurones in the striatum and thus locally regulate dopamine release, a clear demonstration of such a mechanism is lacking and a number of indirect sites of action are possible. We have taken advantage of a simpli¢ed preparation in which cultured rat ventral tegmental area dopaminergic neurones establish nerve terminals that co-release glutamate to determine whether neurotensin can act at presynaptic sites. We recorded glutamatemediated synaptic currents that were generated by dopaminergic nerve terminals as an index of presynaptic function. The neurotensin receptor agonist NT(8^13) caused an inward current and an enhancement of the ¢ring rate of dopaminergic neurones together with an increase in the frequency of spontaneous glutamate receptor-mediated excitatory postsynaptic currents (EPSCs). Incompatible with a direct excitatory action on nerve terminals, NT(8^13) failed to change the amplitude of individual action potential-evoked EPSCs or the frequency of miniature EPSCs recorded in the presence of tetrodotoxin. However, NT(8^13) reduced the ability of terminal D2 dopamine receptors to inhibit action potentialevoked EPSCs in isolated dopaminergic neurones. Taken together, our results suggest that in addition to its well-known somatodendritic excitatory e¡ect leading to an increase in ¢ring rate, neurotensin also acts on nerve terminals. The main e¡ect of neurotensin on nerve terminals is not to produce a direct excitation, but rather to decrease the e¡ectiveness of D2 receptor-mediated presynaptic inhibition. ß

Use of TH-EGFP transgenic mice as a source of identified dopaminergic neurons for physiological studies in postnatal cell culture

“…The excitatory effect of this tridecapeptide on dopaminergic neurons is well established (Legault et al, 2002;Pinnock, 1985;Seutin et al, 1989;St-Gelais et al, 2004). The effect of the active fragment of neurotensin (NT(8-13)) on neuronal excitability was evaluated by whole-cell current-clamp recordings.…”

Role of Calcium in Neurotensin-Evoked Enhancement in Firing in Mesencephalic Dopamine Neurons

“…It acts both at the nerve terminal (Hetier et al, 1988;Faggin et al, 1990;Heaulme et al, 1997;Legault et al, 2002) and at the somatodendritic level in which it enhances firing rate (Pinnock, 1985;Seutin et al, 1989;Jiang et al, 1994;Nalivaiko et al, 1998;Werkman et al, 2000). The effects of NT on DAergic neurons are thought to be primarily mediated by NTS1, a G-protein-coupled receptor that is highly expressed in DAergic neurons (Mazella et al, 1996).…”

Differential cellular and subcellular distribution of glutamate transporters in the cat retina

“…If glutamate is found to be a co-transmitter in these amacrine cells, it would partner with dopamine and GABA, respectively. While not specific to these cell types, there is increasing evidence from other studies for the co-release of dopamine and glutamate (Sulzer et al, 1998;Legault et al, 2002;Chuhma et al, 2004) or GABA and glutamate from single neurons (Docherty et al, 1987;Yang & Yazulla, 1994).…”