GALANIN RECEPTOR-MEDIATED INHIBITION OF GLUTAMATE RELEASE IN THE ARCUATE NUCLEUS OF THE HYPOTHALAMUS

It is thought that galanin, a 29 amino acid neuropeptide, is involved in various neuronal functions, including the regulation of food intake and hormone release. Consistent with this idea, galanin receptors hav e been demonstrated throughout the brain, with high levels being obser ved in the hypothalamus. However, little is known about the mechanisms by which galanin elicits its actions in the brain. Therefore, we stud ied the effects of galanin and its analogs on synaptic transmission us ing an in vitro slice preparation of rat hypothalamus. In arcuate nucl eus neurons, application of galanin resulted in an inhibition of evoke d glutamatergic EPSCs and a decrease in paired-pulse depression, indic ating a presynaptic action. The fragments galanin 1-16 and 1-15 produc ed a robust depression of synaptic transmission, whereas the fragment 3-29 produced a lesser degree of depression. The chimeric peptides C7, M15, M32, and M40, which have been reported to antagonize some action s of galanin, all produced varying degrees of depression of evoked EPS Cs. In a minority of cases, C7, M15, and M40 antagonized the actions o f galanin. Analysis of mEPSCs in the presence of TTX and Cd2+, or afte r application of alpha-latrotoxin, indicated a site of action for gala nin downstream of Ca2+ entry. Thus, our data suggest that galanin acts via several subtypes of presynaptic receptors to depress synaptic tra nsmission in the rat arcuate nucleus.