Brief intro:
- Author: Jian-Ya Peng, Kang-Li Shen, Xiu-Juan Fan, Zeng-Xin Qi, Hui-Wei Huang, Jian-Lan Jiang, Jian-Hua Lu, Xiao-Qin Wang, Xiao-Xia Fang, Wang-Rui Yuan, Qiao-Xuan Deng, Shu Chen, Liang Chen & Qian-Xing Zhuang
- Journal: Molecular Neurobiology
- Doi: https://www.doi.org/10.1007/s12035-022-03076-y
- Publication Date: 2022 Oct 17
Products/Services used in the paper
Quotation shows PackGene:The injection volume of AAV9-CMV-Ncx3 sgRNA-EGFP targeting 5’- GAG CAG AGG CTG GTG ACT CGGGG-3’, 5’- CCT TGG GGA CAA GAT TGC CAGGG-3’, and 5’- TCG GGG GAT GTG CCC AGT GCAGG-3’ (viral titers were 1.0 × 10^13 viral genomes per milliliter, PackGene, Guangzhou, China) or AAV9- CMV-neg-EGFP (control virus, viral titers were 1.32 × 10^13 viral genomes per milliliter, PackGene) was 0.2 μL/site.
Research Field:CNS
AAV Serotype:AAV9
Targeted organ:brain
Animal or cell line strain:Six to 8-week-old B6/JGpt-Drd1em1Cin(P2A−iCre)/Gpt (D1-Cre), B6/JGpt-Drd2em1Cin(P2A−iCre)/Gpt (D2-Cre), and B6/JGpt-Rosa26tm1Cin(CAG−LSL−Cas9−tdTomato)/Gpt mice (LSLCas9-tdTomato)
Abstract
The dorsolateral striatum (DLS) is the critical neural substrate that plays a role in motor control and motor learning. Our past study revealed a direct histaminergic projection from the tuberomammillary nucleus (TMN) of the hypothalamus to the rat striatum. However, the afferent of histaminergic fibers in the mouse DLS, the effect of histamine on DLS neurons, and the underlying receptor and ionic mechanisms remain unclear. Here, we demonstrated a direct histaminergic innervation from the TMN in the mouse DLS, and histamine excited both the direct-pathway spiny projection neurons (d-SPNs) and the indirect-pathway spiny projection neurons (i-SPNs) of DLS via activation of postsynaptic H1R and H2R, albeit activation of presynaptic H3R suppressed neuronal activity by inhibiting glutamatergic synaptic transmission on d-SPNs and i-SPNs in DLS. Moreover, sodium-calcium exchanger 3 (NCX3), potassium-leak channels linked to H1R, and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) coupled to H2R co-mediated the excitatory effect induced by histamine on d-SPNs and i-SPNs in DLS. These results demonstrated the pre- and postsynaptic receptors and their downstream multiple ionic mechanisms underlying the inhibitory and excitatory effects of histamine on d-SPNs and i-SPNs in DLS, suggesting a potential modulatory effect of the central histaminergic system on the DLS as well as its related motor control and motor learning.
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