Whole-brain patterns of the presynaptic inputs and axonal projections of BDNF neurons in the paraventricular nucleus

Fang Luo^{a, #},
Yuling Mu^{a, #},
Cuicui Gao^{a, b, c, #},
Yan Xiao^{d, e},
Qian Zhou^{a, b, c},
Yiqing Yang^a,
Xinyan Ni^a,
Wei L. Shen^{a
, ,},
Jiajun Yang^{d, e
, ,}

a.
Undergraduate Program and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
b.
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
c.
University of Chinese Academy of Sciences, Beijing, 100049, China
d.
Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
e.
Department of Neurology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Science, Shanghai, 201306, China

More Information

Corresponding author: E-mail address: shenwei@shanghaitech.edu.cn (Wei L. Shen); E-mail address: sd_yangjj@sumhs.edu.cn (Jiajun Yang)

These authors contributed equally.

摘要

- /
- /
- /
- /
Abstract: Brain-derived neurotrophic factor (BDNF) plays a crucial role in human obesity. Yet, the neural circuitry supporting the BDNF-mediated control of energy homeostasis remains largely undefined. To map key regions that might provide inputs to or receive inputs from the paraventricular nucleus (PVN) BDNF neurons, a key type of cells in regulating feeding and thermogenesis, we used rabies virus-based transsynaptic labeling and adeno-associated virus based anterograde tracing techniques to reveal their whole-brain distributions. We found that dozens of brain regions provide dense inputs to or receive dense inputs from PVN BDNF neurons, including several known weight control regions and several novel regions that might be functionally important for the BDNF-mediated regulation of energy homeostasis. Interestingly, several regions show very dense reciprocal connections with PVN BDNF neurons, including the lateral septum, the preoptic area, the ventromedial hypothalamic nucleus, the paraventricular thalamic nucleus, the zona incerta, the lateral parabrachial nucleus, the subiculum, the raphe magnus nucleus, and the raphe pallidus nucleus. These strong anatomical connections might be indicative of important functional connections. Therefore, we provide an outline of potential neural circuitry mediated by PVN BDNF neurons, which might be helpful to resolve the complex obesity network.
- BDNF /
- Transsynaptic tracing /
- Obesity /
- Feeding /
- Thermogenesis
These authors contributed equally.
注释:

HTML全文

参考文献(58)

[1]	Altieri, M., Marini, F., Arban, R. et al. Brain Res., 1000 (2004),pp. 148-155
[2]	An, Juan J., Liao, G.-Y., Kinney, Clint E. et al. Discrete BDNF neurons in the paraventricular hypothalamus control feeding and energy expenditure Cell Metabol., 22 (2015),pp. 175-188
[3]	Cai, H., Haubensak, W., Anthony, T.E. et al. Central amygdala PKC-delta neurons mediate the influence of multiple anorexigenic signals Nat. Neurosci., 17 (2014),pp. 1240-1248
[4]	Chometton, S., Charriere, K., Bayer, L. et al. The rostromedial zona incerta is involved in attentional processes while adjacent LHA responds to arousal: c-Fos and anatomical evidence Brain Struct. Funct., 222 (2017),pp. 2507-2525
[5]	Conte, W.L., Kamishina, H., Reep, R.L. Multiple neuroanatomical tract-tracing using fluorescent Alexa Fluor conjugates of cholera toxin subunit B in rats Nat. Protoc., 4 (2009),pp. 1157-1166
[6]	Daigle, T.L., Madisen, L., Hage, T.A. et al. A suite of transgenic driver and reporter mouse lines with enhanced brain-cell-type targeting and functionality Cell, 174 (2018),pp. 465-480
[7]	Doudna, J.A., Charpentier, E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9 Science, 346 (2014),p. 1258096
[8]	Douglass, A.M., Kucukdereli, H., Ponserre, M. et al. Central amygdala circuits modulate food consumption through a positive-valence mechanism Nat. Neurosci., 20 (2017),pp. 1384-1394
[9]	Godar, R., Dai, Y., Bainter, H. et al. Reduction of high-fat diet-induced obesity after chronic administration of brain-derived neurotrophic factor in the hypothalamic ventromedial nucleus Neuroscience, 194 (2011),pp. 36-52
[10]	Gray, J., Yeo, G.S.H., Cox, J.J. et al. Diabetes, 55 (2006),pp. 3366-3371
[11]	Huang, Y.H., Mogenson, G.J. Differential effects of incertal and hypothalamic lesions on food and water intake Exp. Neurol., 43 (1974),pp. 276-280
[12]	Jiang, Z., Rajamanickam, S., Justice, N.J. Local corticotropin-releasing factor signaling in the hypothalamic paraventricular nucleus J. Neurosci., 38 (2018),pp. 1874-1890
[13]	Kishi, T., Elmquist, J.K. Body weight is regulated by the brain: a link between feeding and emotion Mol. Psychiatr., 10 (2005),pp. 132-146
[14]	Krashes, M.J., Lowell, B.B., Garfield, A.S. Melanocortin-4 receptor-regulated energy homeostasis Nat. Neurosci., 19 (2016),pp. 206-219
[15]	Liao, G.Y., An, J.J., Gharami, K. et al. Nat. Med., 18 (2012),pp. 564-571
[16]	Liu, K., Kim, J., Kim, D.W. et al. Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep Nature, 548 (2017),pp. 582-587
[17]	Majeed, N.H., Przewlocka, B., Wedzony, K. et al. Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats Peptides, 7 (1986),pp. 711-716
[18]	Maynard, K.R., Hill, J.L., Calcaterra, N.E. et al. Functional role of BDNF production from unique promoters in aggression and serotonin signaling Neuropsychopharmacology, 41 (2016),pp. 1943-1955
[19]	Menard, J., Treit, D. Lateral and medial septal lesions reduce anxiety in the plus-maze and probe-burying tests Physiol. Behav., 60 (1996),pp. 845-853
[20]	Milner, K.L., Mogenson, G.J. Electrical and chemical activation of the mesencephalic and subthalamic locomotor regions in freely moving rats Brain Res., 452 (1988),pp. 273-285
[21]	Mizuno, S., Dinh, T.T.H., Kato, K. et al. Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system Mamm. Genome, 25 (2014),pp. 327-334
[22]	Mou, Z., Hyde, T.M., Lipska, B.K. et al. Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus Cell Rep., 13 (2015),pp. 1073-1080
[23]	Murer, M.G., Pazo, J.H. Circling behaviour induced by activation of GABAA receptors in the subthalamic nucleus Neuroreport, 4 (1993),pp. 1219-1222
[24]	Perier, C., Tremblay, L., Feger, J. et al. Behavioral consequences of bicuculline injection in the subthalamic nucleus and the zona incerta in rat J. Neurosci., 22 (2002),pp. 8711-8719
[25]	Power, B.D., Leamey, C.A., Mitrofanis, J. Evidence for a visual subsector within the zona incerta Vis. Neurosci., 18 (2001),pp. 179-186
[26]	Ran, F.A., Hsu, P.D., Wright, J. et al. Genome engineering using the CRISPR-Cas9 system Nat. Protoc., 8 (2013),pp. 2281-2308
[27]	Roger, M., Cadusseau, J. Afferents to the zona incerta in the rat: a combined retrograde and anterograde study J. Comp. Neurol., 241 (1985),pp. 480-492
[28]	Sakata, K., Woo, N.H., Martinowich, K. et al. Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex Proc. Natl. Acad. Sci. U. S. A., 106 (2009),pp. 5942-5947
[29]	Scopinho, A.A., Resstel, L.B., Correa, F.M. Alpha(1)-Adrenoceptors in the lateral septal area modulate food intake behaviour in rats Br. J. Pharmacol., 155 (2008),pp. 752-756
[30]	Shaun, F., Morrison, K.N. Central neural pathways for thermoregulation Front. Biosci., 16 (2011),pp. 74-104
[31]	Speliotes, E.K., Willer, C.J., Berndt, S.I. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index Nat. Genet., 42 (2010),pp. 937-948
[32]	Stanley, S., Domingos, A.I., Kelly, L. et al. Profiling of glucose-sensing neurons reveals that GHRH neurons are activated by hypoglycemia Cell Metabol., 18 (2013),pp. 596-607
[33]	Supko, D.E., Uretsky, N.J., Wallace, L.J. Activation of AMPA/kainic acid glutamate receptors in the zona incerta stimulates locomotor activity Brain Res., 564 (1991),pp. 159-163
[34]	Tait, D.S., Phillips, J.M., Blackwell, A.D. et al. Effects of lesions of the subthalamic nucleus/zona incerta area and dorsomedial striatum on attentional set-shifting in the rat Neuroscience, 345 (2017),pp. 287-296
[35]	Tan, C.L., Cooke, E.K., Leib, D.E. et al. Warm-sensitive neurons that control body temperature Cell, 167 (2016),pp. 47-59
[36]	Tan, C.L., Knight, Z.A. Regulation of body temperature by the nervous system Neuron, 98 (2018),pp. 31-48
[37]	Tervo, D.G., Hwang, B.Y., Viswanathan, S. et al. A designer AAV variant permits efficient retrograde access to projection neurons Neuron, 92 (2016),pp. 372-382
[38]	Thorleifsson, G., Walters, G.B., Gudbjartsson, D.F. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity Nat. Genet., 41 (2009),pp. 18-24
[39]	Timmusk, T., Palm, K., Metsis, M. et al. Neuron, 10 (1993),pp. 475-489
[40]	Unger, T.J., Calderon, G.A., Bradley, L.C. et al. Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity J. Neurosci., 27 (2007),pp. 14265-14274
[41]	Vong, L., Ye, C., Yang, Z. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons Neuron, 71 (2011),pp. 142-154
[42]	Walsh, L.L., Halaris, A.E., Grossman, L. et al. Some biochemical effects of zona incerta lesions that interfere with the regulation of water intake Pharmacol. Biochem. Behav., 7 (1977),pp. 351-356
[43]	Wang, C., Bomberg, E., Billington, C. et al. Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reduces energy intake Am. J. Physiol. Regul. Integr. Comp. Physiol., 293 (2007),pp. R1003-R1012
[44]	Wang, C., Bomberg, E., Billington, C.J. et al. Brain-derived neurotrophic factor (BDNF) in the hypothalamic ventromedial nucleus increases energy expenditure Brain Res., 1336 (2010),pp. 66-77
[45]	Wang, C., Bomberg, E., Levine, A. et al. Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake Am. J. Physiol. Regul. Integr. Comp. Physiol., 293 (2007),pp. R1037-R1045
[46]	Wang, D., He, X., Zhao, Z. et al. Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons Front. Neuroanat., 9 (2015),p. 40
[47]	Waterson, M.J., Horvath, T.L. Neuronal regulation of energy homeostasis: beyond the hypothalamus and feeding Cell Metabol., 22 (2015),pp. 962-970
[48]	Wen, W.Q., Cho, Y.S., Zheng, W. et al. Meta-analysis identifies common variants associated with body mass index in east Asians Nat. Genet., 44 (2012),pp. 307-311
[49]	Wickersham, I.R., Lyon, D.C., Barnard, R.J. et al. Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons Neuron, 53 (2007),pp. 639-647
[50]	Xu, B., Goulding, E.H., Zang, K. et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor Nat. Neurosci., 6 (2003),pp. 736-742
[51]	Xu, B., Xie, X. Neurotrophic factor control of satiety and body weight Nat. Rev. Neurosci., 17 (2016),pp. 282-292
[52]	Yadin, E., Thomas, E., Grishkat, H.L. et al. The role of the lateral septum in anxiolysis Physiol. Behav., 53 (1993),pp. 1077-1083
[53]	Yeo, G.S., Connie Hung, C.C., Rochford, J. et al. Nat. Neurosci., 7 (2004),pp. 1187-1189
[54]	Yu, S., Qualls-Creekmore, E., Rezai-Zadeh, K. et al. Glutamatergic preoptic area neurons that express leptin receptors drive temperature-dependent body weight homeostasis J. Neurosci., 36 (2016),pp. 5034-5046
[55]	Zhang, Q., Li, H., Guo, F. Amygdala, an important regulator for food intake Front. Biol., 6 (2011),pp. 82-85
[56]	Zhang, X., van den Pol, A.N. Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation Science, 356 (2017),pp. 853-859
[57]	Zhang, Z., Zhang, H., Wen, P. et al. Whole-Brain Mapping of the inputs and outputs of the medial part of the olfactory tubercle Front. Neural Circuits, 11 (2017),p. 52
[58]	Zhao, Z.D., Yang, W.Z., Gao, C. et al. A hypothalamic circuit that controls body temperature Proc. Natl. Acad. Sci. U. S. A., 114 (2017),pp. 2042-2047

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 111
HTML全文浏览量: 30
PDF下载量: 1
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

doi: 10.1016/j.jgg.2018.11.004

计量

Whole-brain patterns of the presynaptic inputs and axonal projections of BDNF neurons in the paraventricular nucleus

Corresponding author: E-mail address: shenwei@shanghaitech.edu.cn (Wei L. Shen); E-mail address: sd_yangjj@sumhs.edu.cn (Jiajun Yang)

计量

目录

留言板

doi: 10.1016/j.jgg.2018.11.004

计量

出版历程

Whole-brain patterns of the presynaptic inputs and axonal projections of BDNF neurons in the paraventricular nucleus

Corresponding author: E-mail address: shenwei@shanghaitech.edu.cn (Wei L. Shen); E-mail address: sd_yangjj@sumhs.edu.cn (Jiajun Yang)

计量

出版历程

目录