Dynorphin A(1–8) immunoreactive cell bodies, dendrites and terminals are postsynaptic to calcitonin gene-related peptide primary afferent terminals in the monkey dorsal horn

Carlton, Susan M.; Hayes, Elizabeth S.

doi:10.1016/0006-8993(89)91607-7

Cited by 30 publications

(12 citation statements)

References 24 publications

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“…A protocol for immunogold staining has been previously published by our lab (24, 25). Briefly, rats (n=3) were perfused, the brain was removed and the tissue blocks were post fixed, embedded with epon, cured, cut and rinsed.…”

Section: Methodsmentioning

confidence: 99%

Gamma-Aminobutyric Acidergic Projections From the Dorsal Raphe to the Nucleus Accumbens Are Regulated by Neuromedin U

Kasper

McCue

Milton

et al. 2016

Biological Psychiatry

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Introduction Neuromedin U (NMU) is a neuropeptide enriched in the nucleus accumbens shell (NAcSh), a brain region associated with reward. While NMU and its receptor, NMU Receptor 2 (NMUR2), have been studied for its ability to regulate food reward, NMU has not been studied in the context of drugs of abuse (e.g. cocaine). Furthermore, the neuroanatomical pathways which express NMUR2 and its ultrastructural localization are unknown. Methods Immunohistochemistry was used to determine the synaptic localization of NMUR2 in the NAcSh and characterize which neurons express this receptor (n=17). The functional outcome of NMU on NMUR2 was examined using microdialysis (n=16). The behavioral effects of NMU microinjection directly to the NAcSh was investigated using cocaine-evoked locomotion (n=93). The specific effects of NMUR2 knockdown on cocaine-evoked locomotion was evaluated using viral-mediated RNAi (n=40). Results NMUR2 is localized to presynaptic GABAergic nerve terminals in the NAcSh originating from the dorsal raphe nucleus. Furthermore, NMU microinjection to the NAcSh decreased local GABA concentrations. Next, we evaluated the effects of NMU microinjection on behavioral sensitization to cocaine. When repeatedly administered throughout the sensitization regimen, NMU attenuated cocaine-evoked hyperactivity. Additionally, shRNA-mediated knockdown of presynaptic NMUR2 in the NAcSh using a retrograde viral vector potentiated cocaine sensitization. Conclusions Together, these data reveal that NMUR2 modulates a novel GABAergic pathway from the dorsal raphe nucleus to the NAcSh to influence behavioral responses to cocaine.

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Section: Methodsmentioning

confidence: 99%

Gamma-Aminobutyric Acidergic Projections From the Dorsal Raphe to the Nucleus Accumbens Are Regulated by Neuromedin U

Kasper

McCue

Milton

et al. 2016

Biological Psychiatry

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“…Calcitonin gene-related peptide (CGRP), first reported as an alternative expression product of the gene encoding calcitonin (Amara et al, 1982(Amara et al, , 1985Rosenfeld et al, 1983Rosenfeld et al, , 1984, is widely distributed in the central and peripheral sensory nervous systems (Gibson et al, 1984;Skofitsch and Jacobowitz, 1985a;Colin and Kruger, 1986;Peterfreund and Vale, 1986;Carlton et al, 1987;Kuwayama et al, 1987;Kruger, 1987, 1989;Chung et al, 1988;Harmon et al, 1988;Kruger et al, 1988a, b;Carlton and Hayes, 1989;Traub et al, 1989Traub et al, , 1990Hökfelt, 1991;Quartu et al, 1992;Henry et al, 1996). The CGRP-like immunoreactivity (CGRP-ir) is found in a large proportion of small to medium-sized primary neuronal cell bodies (Mason et al, 1984;Skofitsch and Jacobowitz, 1985b;Goodman and Iversen, 1986;McCulloch et al, 1986;Ju et al, 1987) but is rare in autonomic ganglia (Rosenfeld et al, 1983;Landis and Fredieu, 1986).…”

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confidence: 97%

Central projection of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive trigeminal primary neurons in the rat

et al. 1997

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Substance P (SP) is implicated in transmission of primary afferent nociceptive signals. In primary neurons, SP is colocalized with calcitonin gene-related peptide (CGRP), which is another neuropeptide marker for small to medium primary neurons. CGRP coreleased with SP augments the postsynaptic effect of SP and thereby modulates the nociceptive transmission. This study demonstrates the distribution of CGRP-like immunoreactivity (-ir) and SP-ir in the lower brainstem of normal rats and after trigeminal rhizotomy or tractotomy at the level of subnucleus interpolaris (Vi). By comparing the results obtained from normal and deafferented rats, we analyzed the central projection of trigeminal primary nociceptors. The CGRP-immunoreactive (-ir) trigeminal primaries projected to the entire rostrocaudal extent of the spinal trigeminal nucleus, the principal nucleus (PrV), the paratrigeminal nucleus (paraV), and the lateral subnucleus of solitary tract nucleus (STN) on the ipsilateral side. The trigeminal primaries projecting to the spinal trigeminal nucleus, paraV and STN also contained SP-ir. The ipsilateral trigeminal primaries were the exclusive source of CGRP-ir terminals in the PrV, the Vi and the dorsomedial nucleus within the subnucleus oralis (Vo). The medullary dorsal horn (MDH) and the lateral edge of Vo received convergent CGRP-ir projection from the ipsilateral trigeminal primaries and other neurons. The glossopharyngeal and vagal primaries are candidates for the source of CGRP-ir projection to the Vo and the MDH, while the dorsal root axons supply the MDH with CGRP-ir terminals. In addition, contralateral primary neurons crossing the midline appear to contain CGRP and to terminate in the MDH.

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“…Despite this and other physiological evidence for vesicular release of neurotransmitter candidates from the somata of sensory neurons (Huang and Neher 1996;Neubert et al, 2000;Ulrich-Lai et al, 2001;Zhang and Zhou 2002), there is a stark paucity of anatomical data to complement physiological findings. Published electron microscopy (EM) investigations of the cellular organelles in sensory neuron somata do not reveal presence of vesicles in proximity to the plasma membrane of the type that are commonly observed at the synaptic terminal specializations of these neurons in the sympathetic ganglia (Heym et al, 1993), the spinal cord or brainstem (Knyihar-Csillik et al, 1982;Carlton and Hayes 1989;Plenderleith et al, 1990;Valtschanoff et al, 1994), or at the reconstructed peripheral axon terminals of unmyelinated sensory neurons (Kruger et al, 2003). Only one study illustrates a single vesicle in close apposition to the somatic plasma membrane of IB4 (+) neurons (Streit et al, 1986), whereas only scattered cytoplasmic vesicles may be found at considerable distances from the plasma membrane in others (Dixon 1963;Pineda et al, 1967;Peach 1972;Lehtosalo et al, 1984).…”

Section: Anatomical Evidence Of Vesicular Releasementioning

confidence: 99%

“…Their anatomical distributions also differ in that IB4 (+) neurons innervate the epidermis whereas IB4 (-) neurons innervate subcutaneous, joint and visceral structures (Lu et al, 2001;Ivanavicius et al, 2004;Aoki et al, 2005). In the spinal cord, IB4 (+) neurons terminate primarily in the inner lamina II, whereas the IB4 (-) peptidergic nociceptors terminate in lamina I, and outer lamina II (Coimbra et al, 1974;Carlton and Hayes 1989;Silverman and Kruger 1990;Gerke and Plenderleith 2004;Sanderson Nydahl et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Two types of neurotransmitter release patterns in isolectin B4-positive and negative trigeminal ganglion neurons

et al. 2007

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Mammalian nociceptors have been classified into subclasses based on differential neurotrophin sensitivity and binding of the plant isolectin B4 (IB4). Most of the nerve growth factor-responsive IB4-negative (IB4 (-)) nociceptors contain neuropeptides such as substance P and calcitonin gene-related peptide, whereas the glial-derived neurotrophic factor-responsive IB4-positive (IB4 (+)) neurons predominantly lack such neuropeptides. We hypothesized that the differences in neuropeptide content between IB4 (+) and (-) neurons might be reflected in differences in stimulated exocytosis and/or endocytosis. To address this, we monitored the secretory activity of acutely dissociated neurons from adult rat trigeminal ganglia (TRG) using cell membrane capacitance (Cm) measurements and the fluorescent membrane-uptake marker N-(3-triethylammoniumpropyl)-4-(6-(4-(diethylamino)phenyl)hexatrienyl)pyridinium dibromide (FM4-64). Cm measurements were performed under whole-cell voltage clamp and neurons were depolarized from -75 mV to +10 mV to elicit exocytosis. Both types of TRG neurons showed similarly-sized, calcium-dependent increases in Cm, demonstrating that both IB4 (+) and (-) TRG neurons are capable of stimulated exocytosis. However, the peak Cm of IB4 (+) neurons decayed faster toward baseline than that of IB4 (-) neurons. Also, IB4 (+) neurons had stable Cm responses to repeated stimuli whereas IB4 (-) neurons loss their secretory response during repeated stimulation. These data suggested that the IB4 (+) neurons possess a faster rate of endocytosis and vesicle replenishment than IB4 (-) neurons. To test this, we measured vesicle trafficking with the fluorescent membrane dye FM4-64. FM4-64 staining showed that IB4 (-) neurons exhibit a larger pool of endocytosed vesicles than IB4 (+) neurons because the peak fluorescence increases in IB4 (-) neurons were larger but slower than in IB4 (+) neurons. However, the recycled vesicles were released faster in IB4 (+) compared with IB4 (-) neurons. Taken together these data suggest that the IB4 (+) TRG neurons have faster exocytosis and endocytosis than the IB4 (-) neurons.

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Dynorphin A(1–8) immunoreactive cell bodies, dendrites and terminals are postsynaptic to calcitonin gene-related peptide primary afferent terminals in the monkey dorsal horn

Cited by 30 publications

References 24 publications

Gamma-Aminobutyric Acidergic Projections From the Dorsal Raphe to the Nucleus Accumbens Are Regulated by Neuromedin U

Gamma-Aminobutyric Acidergic Projections From the Dorsal Raphe to the Nucleus Accumbens Are Regulated by Neuromedin U

Central projection of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive trigeminal primary neurons in the rat

Two types of neurotransmitter release patterns in isolectin B4-positive and negative trigeminal ganglion neurons

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