SELECTIVE HISTAMINE UPTAKE RESCUES PHOTO-RECEPTOR AND MECHANORECEPTORFUNCTION OF HISTIDINE DECARBOXYLASE-DEFICIENT DROSOPHILA MUTANT

In insects, histamine is found both in the peripheral nervous system ( PNS) and in the CNS and is known to function as a fast neurotransmitte r in photoreceptors that have been shown to express selectively the hd c gene. This gene codes for histidine decarboxylase (HDC), the enzyme for histamine synthesis. Fast neurotransmission requires the efficient removal of the transmitter from the synaptic cleft. Here we identify in Drosophila photo- and mechanoreceptors a histamine uptake mechanism that can restore the function of these receptors in mutants unable to synthesize histamine. When apparent null mutants for the hdc gene imb ibe aqueous histamine solution or are genetically ''rescued'' by a tra nsgene ubiquitously expressing histidine decarboxylase under heat-shoc k control, sufficient amounts of histamine selectively accumulate in p hoto- and mechanoreceptors to generate near-normal electrical response s in second-order visual interneurons and qualitatively to restore wil d-type visual and mechanosensory behavior. This strongly supports the proposal that histamine functions as a fast neurotransmitter also in a certain class of mechanoreceptors. A set of CNS-intrinsic neurons tha t in the wild type contain high concentrations of histamine apparently lacks this uptake mechanism. We therefore speculate that histamine of intrinsic neurons may function as a neuromodulator rather than as a f ast transmitter.