Electrophysiological properties of brain-natriuretic peptide- and gastrin-releasing peptide-responsive dorsal horn neurons in spinal itch transmission

2016 ◽  
Vol 627 ◽  
pp. 51-60 ◽  
Author(s):  
Fumiya Kusube ◽  
Mitsutoshi Tominaga ◽  
Hiroaki Kawasaki ◽  
Fumiyuki Yamakura ◽  
Hisashi Naito ◽  
...  
2020 ◽  
Author(s):  
Tayler D. Sheahan ◽  
Charles A. Warwick ◽  
Louis G. Fanien ◽  
Sarah E. Ross

AbstractThe neurokinin-1 receptor (NK1R, encoded by Tacr1) is expressed in spinal dorsal horn neurons and has been suggested to mediate itch. However, previous studies relied heavily on neurotoxic ablation of NK1R spinal neurons, which limited further dissection of their function in spinal itch circuitry. Thus, we leveraged a newly developed Tacr1CreER mouse line to characterize the role of NK1R spinal neurons in itch. We show that pharmacological activation of spinal NK1R and chemogenetic activation of Tacr1CreER spinal neurons increases itch behavior, whereas pharmacological inhibition of spinal NK1R suppresses itch behavior. We use fluorescence in situ hybridization to characterize the endogenous expression of Tacr1 throughout the superficial and deeper dorsal horn, as well as the lateral spinal nucleus.Retrograde labeling studies from the parabrachial nucleus show that less than 20% of superficial Tacr1CreER dorsal horn neurons are spinal projection neurons, and thus the majority of Tacr1CreER are local interneurons. We then use a combination of in situ hybridization and ex vivo two-photon Ca2+ imaging of the spinal cord to establish that NK1R and the gastrin-releasing peptide receptor (GRPR) are coexpressed within a subpopulation of excitatory superficial dorsal horn neurons. These findings are the first to describe a role for NK1R interneurons in itch and extend our understanding of the complexities of spinal itch circuitry.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Qing-Tao Meng ◽  
Xian-Yu Liu ◽  
Xue-Ting Liu ◽  
Juan Liu ◽  
Admire Munanairi ◽  
...  

Histamine-dependent and -independent itch is conveyed by parallel peripheral neural pathways that express gastrin-releasing peptide (GRP) and neuromedin B (NMB), respectively, to the spinal cord of mice. B-type natriuretic peptide (BNP) has been proposed to transmit both types of itch via its receptor NPRA encoded by Npr1. However, BNP also binds to its cognate receptor, NPRC encoded by Npr3 with equal potency. Moreover, natriuretic peptides (NP) signal through the Gi-couped inhibitory cGMP pathway that is supposed to inhibit neuronal activity, raising the question of how BNP may transmit itch information. Here we report that Npr3 expression in laminae I-II of the dorsal horn partially overlaps with NMB receptor (NMBR) that transmits histaminergic itch via Gq-couped PLCb-Ca2+ signaling pathway. Functional studies indicate that NPRC is required for itch evoked by histamine but not chloroquine (CQ), a nonhistaminergic pruritogen. Importantly, BNP significantly facilitates scratching behaviors mediated by NMB, but not GRP. Consistently, BNP evoked Ca2+ responses in NMBR/NPRC HEK 293 cells and NMBR/NPRC dorsal horn neurons. These results reveal a previously unknown mechanism by which BNP facilitates NMB-encoded itch through a novel NPRC-NMBR cross-signaling in mice. Our studies uncover distinct modes of action for neuropeptides in transmission and modulation of itch in mice.


2002 ◽  
Vol 88 (3) ◽  
pp. 1279-1287 ◽  
Author(s):  
P. Van Damme ◽  
L. Van den Bosch ◽  
E. Van Houtte ◽  
G. Callewaert ◽  
W. Robberecht

AMPA receptor-mediated excitotoxicity has been implicated in the selective motor neuron loss in amyotrophic lateral sclerosis. In some culture models, motor neurons have been shown to be selectively vulnerable to AMPA receptor agonists due to Ca2+influx through Ca2+-permeable AMPA receptors. Because the absence of GluR2 in AMPA receptors renders them highly permeable to Ca2+ ions, it has been hypothesized that the selective vulnerability of motor neurons is due to their relative deficiency in GluR2. However, conflicting evidence exists about the in vitro and in vivo expression of GluR2 in motor neurons, both at the mRNA and at the protein level. In this study, we quantified electrophysiological properties of AMPA receptors, known to be dependent on the relative abundance of GluR2: sensitivity to external polyamines, rectification index, and relative Ca2+ permeability. Cultured rat spinal cord motor neurons were compared with dorsal horn neurons (which are resistant to excitotoxicity) and with motor neurons that survived an excitotoxic insult. Motor neurons had a higher sensitivity to external polyamines, a lower rectification index, and a higher relative Ca2+ permeability ratio than dorsal horn neurons. These findings confirm that motor neurons are relatively deficient in GluR2. The AMPA receptor properties correlated well with each other and with the selective vulnerability of motor neurons because motor neurons surviving an excitotoxic event had similar characteristics as dorsal horn neurons. These data indicate that the relative abundance of GluR2 in functional AMPA receptors may be a major determinant of the selective vulnerability of motor neurons to excitotoxicity in vitro.


1998 ◽  
Vol 79 (3) ◽  
pp. 1583-1586 ◽  
Author(s):  
Y. H. Jo ◽  
M. E. Stoeckel ◽  
R. Schlichter

Jo, Y. H., M. E. Stoeckel, and R. Schlichter. Electrophysiological properties of cultured neonatal rat dorsal horn neurons containing GABA and met-enkephalin-like immunoreactivity. J. Neurophysiol. 79: 1583–1586, 1998. We have developed a culture of neurons dissociated from the most superficial laminae of the neonatal rat spinal cord dorsal horn (DH). By using the perforated patch-clamp technique, we distinguished four types of neurons based on their firing properties in response to intracellular injection of 900 ms lasting current pulses. Type 1 neurons were characterized by a tonic firing. Type 2 neurons displayed marked spike accommodation and fired brief (<500 ms) bursts of action potentials, whereas type 3 neurons fired a single spike. Type 4 neurons exhibited different types of firing patterns, but all of them possessed a time-dependent inwardly rectifying current activated by membrane hyperpolarization. Met-enkephalin-like immunoreactivity (met-ENK-LI) and glutamic acid decarboxylase-like immunoreactivity (GAD-LI) were colocalized in 42% of the neurons ( n = 59), which were previously identified electrophysiologically. Type 1–4 neurons represented respectively 4, 64, 20, and 12% of the population of neurons colocalizing met-ENK-LI and GAD-LI. We conclude that the electrophysiological properties of DH neurons present in our cultures are similar to those described in acute slice or hemisected spinal cord preparations and that met-ENK-LI and GABA-LI are preferentially colocalized in type 2 neurons.


2004 ◽  
Vol 171 (4S) ◽  
pp. 399-400
Author(s):  
Ramaswamy Manikandan ◽  
Calvin Nathaniel ◽  
Ravi Gullipalli ◽  
Adebanji Adeyoju ◽  
Stephen C.W. Brown ◽  
...  

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