Direct inhibitory action of galanin on hypothalamic arcuate nucleus neurones expressing galanin receptor Gal-R1 mRNA

Galanin may act in the regulation of reproduction and feeding behaviour through a direct action on arcuate nucleus (ARC) neurones but evidence for a postsynaptic action is absent. The effects of rat galanin(1-29) on rat ARC neurones were examined during recordings with biocytin-filled sharp microelectrodes from brain slices. Neurones were subsequently visualised and hybridized for the mRNA of the galanin receptor Gal-R1. Current-clamp recordings revealed that ARC neurones displayed a functional heterogeneity in their firing properties. A great majority of neurones showed low-threshold spikes, instantaneous and time-dependent inward rectifications and an outward rectification. Two types of bursting behaviours were recorded, depending on the level of the membrane potential. Galanin (500 nm) elicited a reversible hyperpolarisation with a decrease in the resistance or a decrease in resistance only in 9 of 34 tested neurones, independent of the electrophysiological phenotype. The reversal potential for the galanin response was about -94 mV, near the equilibrium potential for K+. Galantide (10 nM) antagonised the effects which were not blocked by tetrodotoxin, indicating a postsynaptic action. In situ hybridisation revealed that Gal-R1 mRNA occurred in the neurones that responded to galanin, whereas the unresponsive neurones never exhibited the hybridisation signal. This suggests that the responsive neurones possess functional postsynaptic Gal-R1. The study demonstrates for the first time a direct inhibitory action of galanin on ARC neurones, probably mediated by activation of Gal-R1. This action may have important implications for the functioning of neurones involved in the regulation of reproduction and feeding behaviour, such as proopiomelanocortin neurones. Copyright (C) 2003 S. Karger AG, Basel.