μ-opioid receptor modulation of the glutamatergic/GABAergic midbrain inputs to the mouse dorsal hippocampus

神经科学 加巴能 谷氨酸的 谷氨酸受体 兴奋性突触后电位 化学 生物 抑制性突触后电位 受体 生物化学
作者
Haram Kim,Soumil Dey,Gabriella Sekerková,Marco Martina
出处
期刊:The Journal of Neuroscience [Society for Neuroscience]
卷期号:: e0653242024-e0653242024
标识
DOI:10.1523/jneurosci.0653-24.2024
摘要

We used virus-mediated anterograde and retrograde tracing, optogenetic modulation, immuno-staining, in-situ hybridization, and patch clamp recordings in acute brain slices to study the release mechanism and μ-opioid modulation of the dual glutamatergic/GABAergic inputs from the VTA and supramammillary nucleus to the granule cells of dorsal hippocampus of male and female mice. In keeping with previous reports showing that the two transmitters are released by separate active zones within the same terminals, we found that the short-term plasticity and pharmacological modulation of the glutamatergic and GABAergic currents are indistinguishable. We further found that glutamate and GABA release at these synapses are both virtually completely mediated by N- and P/Q-type calcium channels. We then investigated μ-opioid modulation of these synapses and found that activation of μ-opioid receptors strongly inhibits the glutamate and GABA release, mostly through inhibition of presynaptic N-type channels. However, the modulation by μ-opioid receptors of these dual synapses is complex, as it likely includes also a disinhibition due to down-modulation of local GABAergic interneurons which make direct axo-axonic contacts with the dual glutamatergic/GABAergic terminals. We discuss how this opioid modulation may enhance LTP at the perforant path inputs, potentially contributing to reinforce memories of drug-associated contexts. Significance Statement Corelease of an excitatory (glutamate) and an inhibitory (GABA) neurotransmitter from the same synapse is a rare finding in the nervous system and the detailed mechanisms of this transmission are still incompletely described. Here we show that in dual glutamatergic/GABAergic synapses from the midbrain to the dentate gyrus of the dorsal hippocampus similar calcium microdomains control the release of both transmitters. Additionally, we show that activation of μ-opioid receptors limits release by strong inhibition of presynaptic N-type calcium channels in the mixed glutamatergic/GABAergic terminals, while likely potentiating release by inhibition of axo-axonic synapses from local inhibitory interneurons. Modulation of these synapses by μ-opioid receptors might help reinforce memories of drug-associated contexts.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
充电宝应助伍仨仨采纳,获得10
刚刚
卓涵柏发布了新的文献求助10
1秒前
6秒前
wanci应助drift采纳,获得10
7秒前
10秒前
10秒前
郝剑身发布了新的文献求助30
11秒前
15秒前
牛太虚发布了新的文献求助200
15秒前
Stan771完成签到,获得积分10
17秒前
粗犷的沛容应助舒适丹雪采纳,获得10
17秒前
ljty完成签到,获得积分10
17秒前
CipherSage应助Yara.H采纳,获得30
20秒前
英姑应助SUIJI采纳,获得10
20秒前
20秒前
sissiarno应助野椒搞科研采纳,获得30
21秒前
SLS完成签到,获得积分10
25秒前
希望天下0贩的0应助ZMmmm采纳,获得10
25秒前
bluecat发布了新的文献求助10
26秒前
27秒前
独享属于自己的风完成签到,获得积分10
27秒前
27秒前
27秒前
hlll完成签到 ,获得积分10
29秒前
30秒前
LALALADDDD发布了新的文献求助10
31秒前
呼延香之发布了新的文献求助10
32秒前
阿利呀发布了新的文献求助30
33秒前
33秒前
36秒前
37秒前
37秒前
39秒前
李爱国应助lanting采纳,获得10
39秒前
pharpan发布了新的文献求助10
40秒前
LALALADDDD完成签到,获得积分10
42秒前
ZMmmm发布了新的文献求助10
43秒前
43秒前
45秒前
wjkyunqi发布了新的文献求助10
46秒前
高分求助中
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
CLSI EP47 Evaluation of Reagent Carryover Effects on Test Results, 1st Edition 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
Retention of title in secured transactions law from a creditor's perspective: A comparative analysis of selected (non-)functional approaches 500
"Sixth plenary session of the Eighth Central Committee of the Communist Party of China" 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3055707
求助须知:如何正确求助?哪些是违规求助? 2712333
关于积分的说明 7431052
捐赠科研通 2357290
什么是DOI,文献DOI怎么找? 1248745
科研通“疑难数据库(出版商)”最低求助积分说明 606786
版权声明 596144