Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice

Yixiang LIAO; Ziyi ZHENG; Xiaofang CHENG; Ruyi WEN; Jianxia XIA; Shuancheng REN; Chao HE; Zhi'an HU

doi:10.16016/j.2097-0927.202212122

您当前的位置：

首页 >

文章列表页 >

Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice

Neuroscience | 更新时间：2026-01-09

- Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice
- Journal of Army Medical University Vol. 45, Issue 9, Pages: 927-935(2023)
- 作者机构：
  
  1.400038 重庆, 陆军军医大学(第三军医大学)基础医学院生理学教研室, 脑与智能研究院
  2.050499 石家庄, 联勤保障部队第九八〇医院神经内科
  3.857000 西藏日喀则, 陆军第953医院急诊医学科
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation of China(31970945);the Natural Science Foundation for Distinguished Young Scholars of Chongqing(CSTB2022NSCQ-JQX2897)
- DOI：10.16016/j.2097-0927.202212122
  CLC： R-332;R338.27;R338.64
- Received：20 December 2022，
  
  Revised：2023-01-15，
  
  Published：15 May 2023
- 稿件说明：
移动端阅览
Yixiang LIAO, Ziyi ZHENG, Xiaofang CHENG, et al. Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice[J]. Journal of Army Medical University, 2023, 45(9): 927-935.
DOI：

Yixiang LIAO, Ziyi ZHENG, Xiaofang CHENG, et al. Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice[J]. Journal of Army Medical University, 2023, 45(9): 927-935. DOI： 10.16016/j.2097-0927.202212122.

摘要

目的

探究外侧下丘脑(lateral hypothalamus

LH)食欲素(hypocretin

Hcrt)能神经元-内侧内嗅皮层(medial entorhinal cortex

MEC)神经环路对空间记忆的调控作用。

方法

利用光纤记录技术

观察Hcrt能神经元在空间记忆中的活动模式。通过逆行神经示踪技术鉴定Hcrt能神经元与MEC浅层神经元的形态学联系特征。利用化学遗传学及光遗传学技术探究LH

Hcrt

-MEC通路对空间记忆的影响。

结果

光纤记录实验发现LH的Hcrt能神经元在空间记忆相关行为中高水平激活(

0.01)。逆行神经示踪实验发现Hcrt能神经元投射至空间记忆相关的MEC

LH投射至MEC的Hcrt能神经元在空间记忆中激活。化学遗传学抑制LH

Hcrt

-MEC通路明显增加小鼠寻找食物正确空间位置的潜伏期(

0.05)及小鼠寻得食物过程累计错误次数(

0.05)。光遗传学激活LH

Hcrt

-MEC通路显著降低小鼠早期寻找食物正确位置的潜伏期(

0.05)。

结论

Hcrt能神经元参与空间记忆

LH投射至MEC浅层的Hcrt能神经元在空间记忆中激活

化学遗传学抑制LH

Hcrt

-MEC通路损害空间记忆; 光遗传学激活LH

Hcrt

-MEC通路增强空间记忆。

Abstract

Objective

To explore the regulatory effects of hypocretin (Hcrt) neurons in lateral hypothalamus (LH

Hcrt

)-medial entorhinal cortex (MEC) circuit on spatial memory.

Methods

The activity pattern of Hcrt neurons in spatial memory was recorded using

in vivo

fiber photometry.The morphological characteristics of connections between the Hcrt neurons and MEC neurons were identified with retrograde nerve tracer technique.Chemogenetics and optogenetics were subsequently adopted to confirm the effects of LH

Hcrt

-MEC pathway on spatial memory.

Results

The optical fiber recording showed high levels of activation of Hcrt neurons during the spatial memory-related behaviors (

0.01).The retrograde neural tracer test indicated that Hcrt neurons were projected to MEC which was associated with spatial memory

and those projected Hcrt neurons were confirmed being activated in spatial memory.Inhibition of the LH

Hcrt

-MEC pathway by chemogenetics significantly prolonged the latency of mice to find the correct spatial location of food (

0.05)

and increased the number of errors in the process of finding food (

0.05).However

photoactivation of the LH

Hcrt

-MEC pathway by optogenetics remarkably reduced the latency of mice to find the food location at the initial training blocks (

0.05).

Conclusion

Hcrt neurons are involved in spatial memory

and those Hcrt neurons projected from LH to the shallow layer of MEC are activated in spatial memory.Chemogenetic inhibition of the LH

Hcrt

-MEC pathway impairs spatial memory

while optogenetic activation of this pathway enhances the function.

关键词

Keywords

references

BUZSÁKI G, LLINÁS R. Space and time in the brain[J]. Science, 2017, 358(6362): 482-485. DOI: 10.1126/science.aan8869.

BURGESS N. Spatial memory: how egocentric and allocentric combine[J]. Trends Cogn Sci, 2006, 10(12): 551-557. DOI: 10.1016/j.tics.2006.10.005.

EGNOR S E R. Spatial memory: Mice quickly learn a safe haven[J]. Curr Biol, 2017, 27(10): R388-R390. DOI: 10.1016/j.cub.2017.04.007.

BROADBENT N J, SQUIRE L R, CLARK R E. Spatial memory, recognition memory, and the hippocampus[J]. Proc Natl Acad Sci USA, 2004, 101(40): 14515-14520. DOI: 10.1073/pnas.0406344101.

BRUN V H, OTNASS M K, MOLDEN S, et al . Place cells and place recognition maintained by direct entorhinal- hippocampal circuitry[J ] . Science, 2002, 296(5576): 2243-2246. DOI: 10.1126/science.1071089.

TUKKER J J, BEED P, BRECHT M, et al . Microcircuits for spatial coding in the medial entorhinal cortex[J ] . Physiol Rev, 2022, 102(2): 653-688. DOI: 10.1152/physrev.00042.2020.

OBENHAUS H A, ZONG W, JACOBSEN R I, et al . Functional network topography of the media l entorhinal cortex[J ] . Proc Natl Acad Sci USA, 2022, 119(7): e2121655119. DOI: 10.1073/pnas.2121655119.

ARMSTRONG C, WANG J, YEUN LEE S, et al . Target-selectivity of parvalbumin-positive interneurons in layer Ⅱ of medial entorhinal cortex in normal and epileptic animals[J ] . Hippocampus, 2016, 26(6): 779-793. DOI: 10.1002/hipo.22559.

YUN S, REYNOLDS R P, PETROF I, et al . Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive[J ] . Nat med, 2018, 24(5): 658-666. DOI: 10.1038/s41591-018-0002-1.

SAKURAI T, AMEMIYA A, ISHⅡ M, et al . Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior[J ] . Cell, 1998, 92(4): 573-585. DOI: 10.1016/s0092-8674(00)80949-6.

DE LECEA L, KILDUFF T S, PEYRON C, et al . The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity[J ] . Proc Natl Acad Sci USA, 1998, 95(1): 322-327. DOI: 10.1073/pnas.95.1.322.

JACOBSON L H, HOYER D, DE LECEA L. Hypocretins (orexins): The ultimate translational neuropeptides[J]. J Intern Med, 2022, 291(5): 533-556. DOI: 10.1111/joim.13406.

LI S B, JONES J R, DE LECEA L. Hypocretins, neural systems, physiology, and psychiatric disorders[J]. Curr Psychiatry Rep, 2016, 18(1): 7. DOI: 10.1007/s11920-015-0639-0.

FENG H, WEN S Y, QIAO Q C, et al . Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep[J ] . Nat Commun, 2020, 11(1): 3661. DOI: 10.1038/s41467-020-17401-3.

FLANIGAN M E, ALEYASIN H, LI L, et al . Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice[J ] . Nat Neurosci, 2020, 23(5): 638-650. DOI: 10.1038/s41593-020-0617-7.

HIRANO A, HSU P K, ZHANG L, et al . DEC2 modulates orexin expression and regulates sleep[J ] . Proc Natl Acad Sci USA, 2018, 115(13): 3434-3439. DOI: 10.1073/pnas.1801693115.

YANG L, ZOU B, XIONG X, et al . Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice[J ] . J Neurosci, 2013, 33(12): 5275-3284. DOI: 10.1523/JNEUROSCI.3200-12.2013.

DANG R, CHEN Q, SONG J, et al . Orexin knockout mice exhibit impaired spatial working memory[J ] . Neurosci Lett, 2018, 668: 92-97. DOI: 10.1016/j.neulet.2018.01.013.

JAEGER L B, FARR S A, BANKS W A, et al . Effects of orexin-A on memory processing[J ] . Peptides, 2002, 23(9): 1683-1688. DOI: 10.1016/s0196-9781(02)00110-9.

LI S B, DAMONTE V M, CHEN C, et al . Hyperexcitable arousal circuits drive sleep instability during aging[J ] . Science, 2022, 375(6583): eabh3021. DOI: 10.1126/science.abh3021

HOU Z, YANG X, LI Y, et al . Electroacupuncture enhances neuroplasticity by regulating the orexin A-mediated cAMP/PKA/CREB signaling pathway in senescence-accelerated mouse prone 8 (SAMP8) mice[J ] . Oxid Med Cell Longev, 2022, 2022: 8694462. DOI: 10.1155/2022/8694462

VENDRELL M, CURRAN T, MORGAN J I. A gene expression approach to mapping the functional maturation of the hippocampus[J]. Mol brain Res, 1998, 63(1): 25-34. DOI: 10.1016/s0169-328x(98)00248-4.

REN S, WANG Y, YUE F, et al . The paraventricular thalamus is a critical thalamic area for wakefulness[J ] . Science, 2018, 362(6413): 429-434. DOI: 10 .1126/science.aat2512.

VAN CAUTER T, CAMON J, ALVERNHE A, et al . Distinct roles of medial and lateral entorhinal cortex in spatial cognition[J ] . Cereb Cortex, 2013, 23(2): 451-459. DOI: 10.1093/cercor/bhs033.

HUNSAKER M R, CHEN V, TRAN G T, et al . The medial and lateral entorhinal cortex both contribute to contextual and item recognition memory: a test of the binding of items and context model[J ] . Hippocampus, 2013, 23(5): 380-391. DOI: 10.1002/hipo.22097.

CHEN Q, DE LECEA L, HU Z, et al . The hypocretin/orexin system: an increasingly important role in neuropsychiatry[J ] . Med Res Rev, 2015, 35(1): 152-197. DOI: 10.1002/med.21326.

MAHONEY C E, COGSWELL A, KORALNIK I J, et al . The neurobiological basis of narcolepsy[J ] . Nat Rev Neurosci, 2019, 20(2): 83-93. DOI: 10.1038/s41583-018-0097-x.

NEPOVIMOVA E, JANOCKOVA J, MISIK J, et al . Orexin supplementation in narcolepsy treatment: A review[J ] . Med Res Rev, 2019, 39(3): 961-975. DOI: 10.1002/med.21550.

SCAMMELL T E. Narcolepsy[J]. N Engl J Med, 2015, 373(27): 2654-2662. DOI: 10.1056/NEJMra1500587.

MILEYKOVSKIY B Y, KIYASHCHENKO L I, SIEGEL J M. Behavioral correlates of activity in identified hypocretin/orexin neurons[J]. Neuron, 2005, 46(5): 787-798. DOI: 10.1016/j.neuron.2005.04.035.

PEYRON C, TIGHE D K, VAN DEN POL A N, et al . Neurons containing hypocretin (orexin) project to multiple neuronal systems[J ] . J Neurosci, 1998, 18(23): 9996-10015. DOI: 10.1523/jneurosci.18-23-09996.1998.

胡志安, 夏建霞. 觉醒系统的活动对学习记忆的影响[J]. 第三军医大学学报, 2011, 33(11): 1091-1094.

HU Z A, XIA J X. Influence of activities in arousal system on learning and memory[J]. J Third Mil Med Univ, 2011, 33(11): 1091-1094.

HE C, LUO F, CHEN X, et al . Superficial layer-specific histaminergic modulation of medial entorhinal cortex required for spatial learning[J ] . Cereb Cortex, 2016, 26(4): 1590-1608. DOI: 10.1093/cercor/bhu322.

CHOWDHURY A, LUCHETTI A, FERNANDES G, et al . A locus coeruleus-dorsal CA1 dopaminergic circuit modulates memory linking[J ] . Neuron, 2022, 110(20): 3374-3388. e8. DOI: 1 0.1016/j.neuron.2022.08.001.

TAKEUCHI T, DUSZKIEWICZ A J, SONNEBORN A, et al . Locus coeruleus and dopaminergic consolidation of everyday memory[J ] . Nature, 2016, 537(7620): 357-362. DOI: 10.1038/nature19325.

SCAMMELL T E, ARRIGONI E, LIPTON J O. Neural circuitry of wakefulness and sleep[J]. Neuron, 2017, 93(4): 747-765. DOI: 10.1016/j.neuron.2017.01.014.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of Orexin-A injected into medial entorhinal cortex of rats on sleep-wakefulness and spatial memory

Thalamic nucleus reuniens regulates spatial memory via medial entorhinal cortex: a preliminary study

Continuous exposure to 900 MHz electromagnetic field alters spatial memory and blood-brain barrier permeability in rats

Microinjection of adenosine into orexinergic zone of lateral hypothalamus on sleep-wake cycle in rats

Related Author

胡志安

阎洁

陈芳

张丹

夏建霞

何超

齐爱萍

Qin XIAO

Related Institution

Department of Physiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)

⁰