Co‐localized neuropeptide Y and GABA have complementary presynaptic effects on sensory synaptic transmission

Abstract

We have examined the morphological relationship of neuropeptide Y (NPY) and GABAergic neurons in the lamprey spinal cord, and the physiological 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 close appositions with primary afferent axons. Co-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 ultrastructural level. Electron microscopic analysis showed that NPY-immunoreactivity was present throughout the axoplasm, including over dense core vesicles, whereas GABA-immunoreactivity was mainly found over small synaptic vesicles. Synthetic lamprey NPY, and the related peptide, peptide YY, reduced the amplitude of monosynaptic afferent EPSPs in spinobulbar neurons. NPY had no significant effect on the postsynaptic input resistance or membrane potential, the electrical component of the synaptic potential, or the response to glutamate, but it could reduce the duration of presynaptic action potentials, suggesting that it was acting presynaptically. NPY also reduced the excitability of the spinobulbar neurons, suggesting at least one postsynaptic effect. Because NPY and GABA colocalize, we compared the effects of NPY and the GABA(B) agonist baclofen. Both presynaptically reduced EPSP amplitudes, baclofen 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 terminals in the dorsal spinal cord of the lamprey, and that they have complementary actions in modulating sensory inputs.

A neuropeptide Y receptor Y1‐subfamily gene from an agnathan, the European river lamprey

“…The CNS expression of the lamprey receptor, along with earlier studies revealing high expression levels of NPY and PYY in the lamprey CNS [4], clearly motivates further investigation of the possible neuronal functions of the lamprey receptor. The previous description of NPY effects in the lamprey spinal cord [29] encourages studies of the receptor in this context. The expression pattern also suggests that the lamprey receptor could have a role in peripheral functions of the NPY-family peptides, such as regulation of gastrointestinal tract endocrine functions and blood pressure.…”

“…Porcine NPY, p[Leu31,Pro34]NPY, the series of amino terminally truncated pig NPY peptides pNPY , pNPY 13236 , pNPY [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] , pNPY [25][26][27][28][29][30][31][32][33][34][35][36] , pNPY [26][27][28][29][30][31][32][33][34][35][36] , and bovine PP were from Bachem (King of Prussia, PA, USA); p[D-Trp32]NPY was from Peninsula Laboratories Inc. Lamprey peptides were synthesized as described below. BIBP3226 was kindly provided by K. Thomae GmBH, Biberach, Germany.…”

Hypocretinergic Control of Spinal Cord Motoneurons

“…This indicates that Hcrt is capable of acting presynaptically by increasing the release of neurotransmitter, putatively glutamate, from a population of axon terminals that impinge on spinal motoneurons John et al, 2003;Peever et al, 2003). In favor of a postsynaptic action of Hcrt, (1) applied Hcrt produced large-amplitude, long-lasting membrane depolarization, which would not be expected if the mechanism of action were purely presynaptic (Del Negro and Chandler, 1998;Parker et al, 1998), and (2) preliminary anatomical data indicate that Hcrt-containing fibers are apposed to lumbar motoneurons and that these cells contain Hcrt membrane receptors . A physiological postsynaptic effect induced by Hcrt is peculiar, because most peptides are colocalized with and act to alter the release of classic neurotransmitters (Lohof et al, 1993;Li et al, 1998).…”

GABAergic Neurons that Contain Neuropeptide Y Selectively Target Cells with the Neurokinin 1 Receptor in Laminae III and IV of the Rat Spinal Cord

“…In the lamprey spinal cord, N PY-immunoreactive axons (many of which also contain GABA) form close associations with primary afferents (Bongianni et al, 1990). Parker et al (1998) have recently demonstrated that N PY not only acted presynaptically to reduce the amplitude of primary afferentevoked EPSPs on spinobulbar neurons but also decreased the excitability of these neurons, which was thought to be a postsynaptic action. Spinobulbar neurons in the lamprey appear to be homologous with spinothalamic neurons in mammals, and some of the lamina III / IV N K1 receptor-immunoreactive neurons in the rat belong to this tract (Marshall et al, 1996).…”