Evidence for a negative ultrashort loop feedback regulating galanin release from the arcuate nucleus-median eminence functional unit.

Recent studies from our laboratory have demonstrated that galanin (GAL) is a member of the hypothalamic-hypophysiotropic hormone family. Most of the hypothalamic hormones regulate their own secretion rate by ultrashort loop feedback mechanisms. The purpose of these studies was to evaluate the possibility that hypothalamic GAL could regulate its own release through a similar mechanism. Galanin secretion from median eminence (ME) fragments incubated in vitro increased exponentially with time, whereas GAL release from arcuate nucleus-ME (AN-ME) fragments depicted a secretory profile consisting of an initial exponential rising phase, followed by a plateau phase in which GAL secretion was apparently abolished. Moreover, preexposure of AN-ME fragments to porcine GAL (pGAL) increased tissue responsiveness to K(+)-induced depolarization, suggesting that pGAL reduced the gain of the system. Thus, after pGAL removal, AN-ME fragments appear to be more sensitive to the depolarizing stimulus. In addition, blockade of GAL biological activity in vivo by administration of a sheep antirat GAL serum increased GAL release from AN-ME fragments in vitro, whereas this treatment did not affect GAL release from ME terminals. These results indicate that GAL neurons may diminish their own activity, establishing, therefore, a negative ultrashort loop feedback that controls the firing of the AN galaninergic network and maintains a balanced physiological status. By means of electron microscopy, we demonstrated that GAL-containing perikarya and proximal dendrites receive synapsing axons immunoreactive for the same peptide in the AN, which provides the anatomical basis for interactions between galaninergic neurons. In conclusion, our data support the notion that the galaninergic system, as other peptidergic neurotransmitters, is able to regulate its own release via a negative ultrashort loop feedback control mechanism that is operative at the level of the AN.