Neurotensin-induced excitation of neurons of the rat's frontal cortex studied intracellularly in vitro.

Abstract

The actions of neurotensin (NT) on frontal pyramidal neurons were studied in vitro in slices of rat cerebral cortex using current clamp and single electrode voltage clamp (SEVC) techniques. Bath application of NT (0.1 microM-10 microM) induced a depolarization (2-13 mV) in 88% of the pyramidal cells, this effect was associated with a decrease in input conductance of 5-35% and its reversal potential was estimated at -88 +/ -9.7 mV. Typically, this depolarizing effect of NT was transient, since no cell responded to a second application of the peptide within 20 min after the first one. NT also induced an increase in the rate of firing of pyramidal cells evoked by direct stimulation, even when an hyperpolarizing current was applied to prevent the depolarization induced by NT. This effect could neither be explained by a decrease of the post-spike after-hyperpolarization, nor by an increase of the persistent sodium current which sustains the spiking of pyramidal cells, since the former was not affected consistently by NT and the later was insensitive to the peptide. This excitation of pyramidal neurons by NT persisted after blockade of synaptic transmission. On the other hand, NT also enhanced the synaptic noise recorded in pyramidal cells in standard perfusing medium. Furthermore, dopaminergic antagonists and noradrenergic antagonists failed to block these effects of NT. Finally, the inactive fragment of the peptide, NT(1-8), did not affect membrane properties of pyramidal cells. All together, these results suggest that NT excites frontal cortical neurons through the activation of specific NT receptors.