Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord.
Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord.
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DOI：
10.1038/s41598-023-38605-9
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发表时间：
2023-07-18
影响因子：
4.6
通讯作者：
Hughes, David I.
中科院分区：
文献类型：
--
作者：
Davis, Olivia C.;Dickie, Allen C.;Mustapa, Marami B.;Boyle, Kieran A.;Browne, Tyler J.;Gradwell, Mark A.;Smith, Kelly M.;Polgar, Erika;Bell, Andrew M.;Kokai, Eva;Watanabe, Masahiko;Wildner, Hendrik;Zeilhofer, Hanns Ulrich;Ginty, David D.;Callister, Robert J.;Graham, Brett A.;Todd, Andrew J.;Hughes, David I.
无髓鞘的非肽能性伤害感受器（NP传入）在脊髓II层产生并接受gaba能轴突突触，介导突触前抑制。然而，到目前为止，这种轴突突触输入的来源尚不清楚。在这里，我们提供的证据表明，它起源于一群抑制性钙素表达的中间神经元（iCRs），这对应于II层胰岛细胞。NP事件可以被分配到3个功能不同的类（NP1-3）。NP1事件与病理性疼痛状态有关，而NP2和NP3事件也作为瘙痒受体起作用。我们的研究结果表明，所有这3种传入类型支配iCRs并从它们接收轴突突触，提供对NP输入的反馈抑制。iCRs也形成轴突突触，它们的目标包括自身受NP传入神经支配的细胞，从而允许前馈抑制。因此，iCRs被理想地置于控制非肽能性伤害感受器和瘙痒感受器对其他背角神经元的输入的位置，因此代表了治疗慢性疼痛和瘙痒的潜在治疗靶点。
Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1–3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.
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DOI：
10.1126/science.aac8653
发表时间：
2015-10-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bourane S;Duan B;Koch SC;Dalet A;Britz O;Garcia-Campmany L;Kim E;Cheng L;Ghosh A;Ma Q;Goulding M
通讯作者：
Goulding M
影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
16.2
作者：
Foster, Edmund;Wildner, Hendrik;Tudeau, Laetitia;Haueter, Sabine;Ralvenius, William T.;Jegen, Monika;Johannssen, Helge;Hoesli, Ladina;Haenraets, Karen;Ghanem, Alexander;Conzelmann, Karl-Klaus;Boesl, Michael;Zeilhofer, Hanns Ulrich
通讯作者：
Zeilhofer, Hanns Ulrich
影响因子：
5.5
作者：
Graham, BA;Brichta, AM;Callister, RJ
通讯作者：
Callister, RJ
影响因子：
7.4
作者：
Graham BA;Hughes DI
通讯作者：
Hughes DI