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Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees

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Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 21))

Abstract

This article focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined from brain tissue to the original locations within the brain that they are derived from using digital atlas mapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomic analyses conducted in the mammalian hypothalamus. Following a brief historical overview, we highlight studies that have mined biochemical and molecular information from the hypothalamus and then lay out a strategy for how these data can be linked spatially to the mapped locations in a canonical brain atlas where the data come from, thereby allowing researchers to integrate these data with other datasets across multiple scales. A key methodology that enables atlas-based mapping of extracted datasets—laser-capture microdissection—is discussed in detail, with a view of how this technology is a bridge between systems biology and systems neuroscience.

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Abbreviations

ACB:

nucleus accumbens

AchE:

acetylcholinesterase

ADP:

anterodorsal preoptic nucleus

AgRP:

Agouti-Related Peptide

AHN:

anterior hypothalamic nucleus

AHNa:

anterior hypothalamic nucleus, anterior part

AHNc:

anterior hypothalamic nucleus, central part

AHNd:

anterior hypothalamic nucleus, dorsal part

AHNp:

anterior hypothalamic nucleus, posterior part

AP:

area postrema

ARH:

arcuate hypothalamic nucleus

ATN:

anterior nuclei, dorsal thalamus

AVP:

anteroventral preoptic nucleus

AVPV:

anteroventral periventricular nucleus hypothalamus

BST:

bed nuclei of the stria terminalis

BSTal:

bed nuclei of the stria terminalis, anterior division, anterolateral area

BSTam:

bed nuclei of the stria terminalis, anterior division, anteromedial area

BSTdm:

bed nuclei of the stria terminalis, anterior division, dorsomedial nucleus

BSTfu:

bed nuclei of the stria terminalis, anterior division, fusiform nucleus

BSTif:

bed nuclei of the stria terminalis, posterior division, interfascicular nucleus

BSTju:

bed nuclei of the stria terminalis, anterior division, juxtacapsular nucleus

BSTmg:

bed nuclei of the stria terminalis, anterior division, magnocellular nucleus

BSTov:

bed nuclei of the stria terminalis, anterior division, oval nucleus

BSTpr:

bed nuclei of the stria terminalis, posterior division, principal nucleus

BSTrh:

bed nuclei of the stria terminalis, anterior division, rhomboid nucleus

BSTtr:

bed nuclei of the stria terminalis, posterior division, transverse nucleus

BSTv:

bed nuclei of the stria terminalis, anterior division, ventral nucleus

C.a.:

anterior commissure

C.f.d.:

fornix

CCK1R:

cholecystokinin 1 receptor

Ch. Opt.:

optic chiasm

CRH:

corticotropin-releasing hormone

CTB:

cholera toxin subunit b

DMH:

dorsomedial hypothalamic nucleus

EGFP:

enhanced green fluorescent protein

FG:

fluorogold

fx:

fornix

GFP:

freen fluorescent protein

HNS:

hypothalamo-neurohypophysial system

I:

internuclear area, hypothalamic periventricular region

KO:

knockout

LCM:

laser-capture microdissection

LHA:

lateral hypothalamic area

LHAai:

lateral hypothalamic area, anterior region, intermediate zone

LHAav:

lateral hypothalamic area, anterior region, ventral zone

LHAd:

lateral hypothalamic area

LHAjd:

lateral hypothalamic area, juxtadorsomedial region

LHAjp:

lateral hypothalamic area, juxtaparaventricular region

LHAjvd:

lateral hypothalamic area, juxtaventromedial region, dorsal zone

LHAjvv:

lateral hypothalamic area, juxtaventromedial region, ventral zone

LHApc:

lateral hypothalamic area, parvicellular region

LHAsfa:

lateral hypothalamic area, subfornical region, anterior zone

LPO:

lateral preoptic area

LS:

lateral septal nucleus [Cajal]

LSc.d:

lateral septal nucleus, caudal part, dorsal zone

LSc.v:

lateral septal nucleus, caudal part, ventral zone

LSr.dl:

lateral septal nucleus, rostral part, dorsolateral zone

LSr.m:

lateral septal nucleus, caudal part, medial zone

LSr.vl:

lateral septal nucleus, rostral part, ventrolateral zone

LSv:

lateral septal nucleus, ventral part [Risold-Swanson]

MC4-R:

melanocortin 4 receptor

ME:

median eminence

MEex:

median eminence, external lamina

MEin:

median eminence, internal lamina

MEPO:

median preoptic nucleus

MID:

midline nuclei, dorsal thalamus

MM:

medial mammillary nucleus, body

MNs:

magnocellular neurons

MPN:

medial preoptic nucleus

MPNc:

medial preoptic nucleus, central part

MPNl:

medial preoptic nucleus, lateral part

MPNm:

medial preoptic nucleus, medial part

MPO:

medial preoptic area

MS:

medial septal nucleus [Cajal]

NDB:

diagonal band nucleus [Broca]

NPY:

neuropeptide Y

NTS:

nucleus of the solitary tract

opt:

optic tract

OT:

oxytocin

PCR:

polymerase chain reaction

PFA:

paraformaldehyde

PMd:

dorsal premammillary nucleus

PMv:

ventral premammillary nucleus

POMC:

pro-opiomelanocortin

PR:

perireuniens nucleus

PSCH:

suprachiasmatic preoptic nucleus

PT:

paratenial nucleus

PVH:

paraventricular hypothalamic nucleus

PVHd:

paraventricular hypothalamic nucleus, descending division

PVHf:

paraventricular hypothalamic nucleus, descending division, forniceal part

PVHm:

paraventricular hypothalamic nucleus, magnocellular division

PVHmpd:

paraventricular hypothalamic nucleus, medial parvicellular part, dorsal zone

PVHp:

paraventricular hypothalamic nucleus, parvicellular division

PVHpv:

paraventricular hypothalamic nucleus, periventricular part

PVi:

periventricular hypothalamic nucleus, intermediate part

PVp:

periventricular hypothalamic nucleus, posterior part

PVpo:

preoptic periventricular nucleus

PVR:

hypothalamic periventricular region

PVT:

paraventricular thalamic nucleus

qPCR:

quantitative polymerase chain reaction

RCH:

retrochiasmatic area, lateral hypothalamic area

RE:

nucleus reuniens [Malone]

REcd:

nucleus reuniens, caudal division, dorsal part

REcm:

nucleus reuniens, caudal division, medial part [Gurdjian]

REcp:

nucleus reuniens, caudal division, posterior part

RIN:

RNA integrity number

S.t.:

infundibular stalk

SBPV:

subparaventricular zone hypothalamus

SCH:

suprachiasmatic nucleus [Spiegel-Zwieg]

SFO:

subfornical organ

SMT:

submedial nucleus thalamus

SO:

supraoptic hypothalamic nucleus

SOr:

supraoptic nucleus, retrochiasmatic part

sup:

supraoptic commissures

T.M.:

tractus Meynert (fasciculus retroflexus)

TH:

tyrosine hydroxylase

TUi:

tuberal nucleus, intermediate part

TUsv:

tuberal nucleus, subventricular part

V.d’A.:

tract of Vicq D’Azyr (mammillothalamic tract)

V3 h:

third ventricle, hypothalamic part

vlt:

ventrolateral hypothalamic tract

VMH:

ventromedial hypothalamic nucleus

VMHa:

ventromedial hypothalamic nucleus, anterior part

VMHc:

ventromedial hypothalamic nucleus, central part

VMHdm:

ventromedial hypothalamic nucleus, dorsomedial part

VMHvl:

ventromedial hypothalamic nucleus, ventrolateral part

VP:

vasopressin

VPL:

ventral posterolateral nucleus thalamus, principal part

VPM:

ventral posteromedial nucleus thalamus, principal part

μ-array:

microarray

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Acknowledgments

We thank Dr. Sabiha Khan (UTEP) for thoughtful discussion on the organization of the manuscript, and Dr. Harold Gainer (National Institute of Neurological Disorders and Stroke) for his timely feedback. We would like to thank the anonymous reviewer who provided critical and constructive feedback on an earlier draft of this manuscript. We also acknowledge our debt to the late Dr. Claude F. Baxter, who served as Emeritus Professor of Psychiatry and Biobehavioral Sciences at the UCLA Brain Research Institute and past historian of the American Society for Neurochemistry, for having generously provided AMK access to his personal library of seminal works in neurochemistry. His kindness and hospitality are treasured memories. We would also like to acknowledge the contributions of Dr. Rebecca Hull and Nishi Gill for the images provided in Fig. 6.2B, C. Finally, we thank Dr. Alexander C. Jackson (University of Connecticut) for providing us with access to unpublished data from his single-cell transcriptomic studies of neuron populations in the mouse lateral hypothalamic area. This chapter is dedicated to the memory of Dr. John H. Ashe (University of California, Riverside), whose instruction and mentorship have deeply informed this narrative.

Funding

Work in the UTEP Systems Neuroscience Laboratory is supported by grants awarded to AMK from the National Institutes of Health (NIH; SC3GM109817 and SC1GM127251), the Howard Hughes Medical Institute (UTEP PERSIST Education Grant; PI: S. Aley), and the UTEP Office of Research and Sponsored Projects (Grand Challenges Award). This work is also supported by funds awarded to the Border Biomedical Research Center by the National Institute of Minority Health and Health Disparities of the NIH (5G12MD007592). AHG is supported by the Research Initiative for Scientific Enhancement (RISE) Graduate Fellowship program of the NIH (R25GM069621). AM has been supported by UTEP PERSIST funds and an NSF GK–12 fellowship. Some data in this study were also based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA); specifically, by Merit Review Awards 1l01BX001213-01A1 and BX004102-01 from the United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service to JEB as well as NIH R01DK115976 to JEB. The contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. Government. This study was also supported by the University of Washington Diabetes Research Center Cellular and Molecular Imaging Core, which is supported by NIH grant P30DK017047. The contribution by GAPCB to this work was funded by the Defense Advanced Research Projects Agency (DARPA) Big Mechanism program under Army Research Office (ARO) contract W911NF-1-0436 and by NIH grant R01LM012592.

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Correspondence to Arshad M. Khan .

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Khan, A.M. et al. (2018). Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees. In: Cheung-Hoi Yu, A., Li, L. (eds) Systems Neuroscience. Advances in Neurobiology, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-319-94593-4_6

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