CO-LOCALIZED NEUROPEPTIDE-Y AND GABA HAVE COMPLEMENTARY PRESYNAPTIC EFFECTS ON SENSORY SYNAPTIC TRANSMISSION

We have examined the morphological relationship of neuropeptide Y (NPY ) and GABAergic neurons in the lamprey spinal cord, and the physiologi cal effects of NPY and GABA(B) receptor agonists on afferent synaptic transmission. NPY-containing fibres and cell bodies were identified in the dorsal root entry zone. NPY immunoreactive (-ir) fibres made clos e appositions with primary afferent axons. Go-localization of NPY and GABA-ir was found in the dorsal horn and dorsal column. Fifty-two per cent of NPY-ir profiles showed immunoreactivity to GABA at the ultrast ructural level. Electron microscopic analysis showed that NPY-immunore activity was present throughout the axoplasm, including over dense cor e vesicles, whereas GABA-immunoreactivity was mainly found over small synaptic vesicles. Synthetic lamprey NPY, and the related peptide, pep tide YY, reduced the amplitude of monosynaptic afferent EPSPs in spino bulbar neurons. NPY had no significant effect on the postsynaptic inpu t resistance or membrane potential, the electrical component of the sy naptic potential, or the response to glutamate, but it could reduce th e duration of presynaptic action potentials, suggesting that it was ac ting presynaptically. NPY also reduced the excitability of the spinobu lbar neurons, suggesting at least one postsynaptic effect. Because NPY and GABA colocalize, we compared the effects of NPY and the GABA(B) a gonist baclofen, Both presynaptically reduced EPSP amplitudes, baclofe n having a larger effect and a faster onset and recovery than NPY, The GABA(B) antagonist phaclofen reduced the effect of baclofen, but not that of NPY. We conclude that NPY and GABA are colocalized in terminal s in the dorsal spinal cord of the lamprey, and that they have complem entary actions in modulating sensory inputs.