Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Anatomical Markers of Activity in Hypothalamic Neurons

Gloria E. Hoffman

10.1002/cphy.c170021

Source: Volume 10, Issue 2, April 2020

Published online: March 2020

Full Article on Wiley Online Library



Abstract

The scientific community has searched for years for ways of examining neuronal tissue to track neural activity with reliable anatomical markers for stimulated neuronal activity. Existing studies that focused on hypothalamic systems offer a few options but do not always compare approaches or validate them for dependence on cell firing, leaving the reader uncertain of the benefits and limitations of each method. Thus, in this article, potential markers will be presented and, where possible, placed into perspective in terms of when and how these methods pertain to hypothalamic function. An example of each approach is included. In reviewing the approaches, one is guided through how neurons work, the consequences of their stimulation, and then the potential markers that could be applied to hypothalamic systems are discussed. Approaches will use features of neuronal glucose utilization, water/oxygen movement, changes in neuron‐glial interactions, receptor translocation, cytoskeletal changes, stimulus‐synthesis coupling that includes expression of the heteronuclear or mature mRNA for transmitters or the enzymes that make them, and changes in transcription factors (immediate early gene products, precursor buildup, use of promoter‐driven surrogate proteins, and induced expression of added transmitters. This article includes discussion of methodological limitations and the power of combining approaches to understand neuronal function. © 2020 American Physiological Society. Compr Physiol 10:549‐575, 2020.

Keywords: pathway; physiological genomics; excitation; neurophysiology

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. (A) Autoradiogram of 14C 2‐deoxyglucose (2‐DG) on a slice containing the suprachiasmatic nuclei (SCN) that was obtained during the subjective day; (B) a slice taken from an identical area obtained during the subjective night; and (C) a Nissl‐stained section of the same area as B verifying the presence of the SCN. Note that the signal, while clear, does not easily enable resolution of separate cells. Adapted, with permission, from Newman GC, et al., 1992 118. Copyright 1992, Society for Neuroscience.
Figure 2. Figure 2. (A) fMRI changes (red) in the posterior hypothalamus that correlated with social dominance in macaque monkeys. (B) Correlation of the level of activation with behavioral measures of social dominance. Adapted, with permission, from Noonan MP, et al., 2014 120.
Figure 3. Figure 3. Example of glial‐neuron changes in the supraoptic nucleus of (A) an normal female rat with a clear astrocytic investment (as) around the neuron and (B) a lactating rat in which multiple synapses (arrows) are observed when the glial investment of the neuron is withdrawn. Adapted, with permission, from Theodosis DT, et al., 2004 151.
Figure 4. Figure 4. Indirect evidence for the presence of gap junctions between neurons (A and C) through detection of coupled neurons after a fluorescent dye is injected into only one of the two neurons. (B and D) Cells that appear to lack gap junction communication. Adapted, with permission, from Hatton GI and Yang QZ, 2001 56.
Figure 5. Figure 5. Dendrodendritic interactions in GnRH neurons. Intercellular bridges are seen between GnRH dendrites. (A) Examples of dendritic processes from a rhesus monkey whose bridges between immunoreactive GnRH neurons appear as fine ladders (Hoffman G, unpublished data). (B) Example of two intercellular bridges across GnRH neurons in a rat brain (red circle). (C) Dendritic bundling between two (arrowheads) or three dendrites (arrows) of GnRH neurons labeled with either green fluorescent protein (colored green) or injected biocytin (colored red or yellow). Adapted, with permission, from Campbell RE, et al., 2009 14.
Figure 6. Figure 6. Example of μ‐opiate receptor (MOR) translocation in response to estrogen treatment. (A) Ovariectomized female rat (OVX); (B) OVX rat treated with estradiol benzoate (50 μg, EB). This approach is used as evidence that a receptor ligand has affected neuronal activity. Adapted, with permission, from Eckersell CB, et al., 1998 36. Copyright 1998 Society for Neuroscience.
Figure 7. Figure 7. Spines on kisspeptin neurons of the arcuate nucleus are abundant in ovariectomized animals (A–C) in contrast to ovariectomized animals given estrogen replacement (D). The relationship of the spine patterns to firing dynamics of the neurons leads to the use of spine morphology as a marker of the neuron's activity. Adapted, with permission, from Cholanian M, et al., 2015 20.
Figure 8. Figure 8. Changes in the expression of the cytoskeletal protein, activity‐regulated cytoskeletal protein (Arc/Arg3.1), reflect changes in neuron activity. The figure shows induced ARC/Arg3.1 expression in the suprachiasmatic nucleus in response to lights on in a mouse at 0, 60, 120, 180, and 300 min after lights on. Adapted, with permission, from Nishimura M, et al., 2003 119.
Figure 9. Figure 9. Vasopressin mRNA in neurons of the supraoptic nucleus in a control normonatremic animal (A and B) and after 7 days of hyponatremia. Hyponatremia, a treatment that reduces firing of vasopressin neurons, reduces markedly mRNA expression in the neurons. C and D are higher magnifications of the cells. The bar graph (E) compares the mRNA levels determined from in situ hybridization to those of solution hybridization analysis for vasopressin (Exon C). Hyponatremia significantly decreased mRNA for vasopression (**p < 0.001). The magnitude of suppression with the two detection methods was similar. Adapted, with permission, from Hoffman G, et al., 1995 63.
Figure 10. Figure 10. Tyrosine hydroxylase (TH) RNA levels in continuously suckling rats (0 h) and at 1.5, 6, 12, and 24 h after pup removal reveal initial nuclear sites (heteronuclear RNA) in the first hours after pup removal, and then gradual reexpression of mature mRNA in the cell cytoplasm to levels seen in cycling rats at the later times. Adapted, with permission, from Berghorn KA, et al., 2001 6.
Figure 11. Figure 11. Staining of the protein prohormone for vasopressin and oxytocin is low under baseline conditions (A), but after hypernatremia (B) is strikingly elevated in the supraoptic nucleus. Adapted, with permission, from Verbalis JG, et al., 1991 155.
Figure 12. Figure 12. Examples of the use of promoter‐driven flag expression. a) Example of use of the vasopressin promoter to drive expression of green fluorescent protein (GFP) to enable detection of changes in vasopressin's synthetic activity in chronically salt‐loaded rats. Compared to controls (A–C), expression of the GFP in the SON, PVN, and internal zone of the median eminence of salt‐loaded rats is strikingly elevated (D–F). Adapted, with permission, from Suzuki H, et al., 2009 146. b) Changes in a flag linked to the activity‐depended cytoskeletal protein ARC in the parvocellular PVN (circle) in a control rat (A), a rat exposed to an acute restraint stress (B), or a rat exposed to repeated restraint stress (C). (D) A rat exposed to an immune challenge (lipopolysaccharide, LPS) 3 h earlier. (E) An LPS animal after 6 h. (F) An animal stimulated by both repeated restraint and LPS. (G) A higher magnification of (F) revealing the GFP flag for ARC. (H) Labeling of the same section for CRH. (I) The double labeling of ARC (green) and CRH. Adapted, with permission, from Grinevich V, et al., 2009 53.
Figure 13. Figure 13. Aberrant expression of surrogate proteins. The fact that all cells of the body have the same DNA can result in expression of a surrogate protein in cells that would normally not express that protein. The likely explanation for this is that the insertion of a transgene under a defined promoter lacks sequences that would normally suppress the protein. The figure illustrates examples of aberrant expression of GnRH‐directed green fluorescent protein in populations of neurons that normally would not express GnRH in the lateral hypothalamus (A, black box) and in the dorsal septal area (B, white box). Hoffman G, unpublished data.
Figure 14. Figure 14. Direct assay of mRNA expression. (A) Striking changes in the mRNA for tyrosine hydroxylase detected by radioactive in situ hybridization technology in cycling, lactating rats, and lactating rats whose pups were removed for 24 h. Reused, with permission, from Wang HJ, et al., 1993 158. That neural activity determines the suppression of TH mRNA during suckling in the arcuate nucleus is illustrated after blocking nipples on only one side of the body as illustrated in B. In C, TH mRNA is upregulated back to baseline levels in the arcuate nucleus only on the side contralateral to the nipple blockade. Like other somatosensory paths to the thalamus, the course from the nipples to the thalamus also crosses. Reused, with permission, from Berghorn KA, et al., 2001 6.
Figure 15. Figure 15. Example of a dose‐response in the induction of Fos (left figures) in oxytocin neurons (right figures) after graded treatment with cholecystokinin. Reused, with permission, from Verbalis JG, et al., 1991 156.
Figure 16. Figure 16. Example of the monitoring of fluorescent Ca++ sensitive dyes in electrically stimulated suprachiasmatic nucleus neurons from slice preparations. Reused, with permission, from Irwin RP and Allen CN, 2013 73.
Figure 17. Figure 17. Example of the induction of galanin (black) in GnRH neurons following a surge in the GnRH system. Interestingly, the GnRH in the neurons (brown) is not markedly changed. Hoffman G, unpublished data. Activity dependence of this phenomenon is seen when the GnRH system's surge is delayed for 24 h and delays the galanin expression.
Figure 18. Figure 18. Examples of the changes in CRH hnRNA and that of vasopressin in neurons of the parvocellular PVN after a single or repeated restraint stress. The upper panels (A–D) present CRH hnRNA, and the lower panels (E–H) vasopressin hnRNA. (A) control naïve rat, (B) single restraint, (C) basal CRH expression before repeated restraint, and (D) CRH hnRNA after 14 restraint episodes. Note that CRH hnRNA is elevated by acute restraint but is suppressed after repeated stress (either before or after the last restraint). (E) The expression of vasopressin hnRNA is low in the parvocellular PVN (MP) of naïve rats. However, after a single or multiple episodes of restraint, the vasopressin hnRNA is elevated (F–H). Reused, with permission, from Aguilera G, et al., 2008 1.
Figure 19. Figure 19. Effective use of timing differences in expression of hnRNA versus cytoplasmic mRNA for tyrosine hydroxylase following administration of a glutamate agonist. (A) Control; (B) 1 h after delivery of NMDA. Hoffman G, unpublished data.


Figure 1. (A) Autoradiogram of 14C 2‐deoxyglucose (2‐DG) on a slice containing the suprachiasmatic nuclei (SCN) that was obtained during the subjective day; (B) a slice taken from an identical area obtained during the subjective night; and (C) a Nissl‐stained section of the same area as B verifying the presence of the SCN. Note that the signal, while clear, does not easily enable resolution of separate cells. Adapted, with permission, from Newman GC, et al., 1992 118. Copyright 1992, Society for Neuroscience.


Figure 2. (A) fMRI changes (red) in the posterior hypothalamus that correlated with social dominance in macaque monkeys. (B) Correlation of the level of activation with behavioral measures of social dominance. Adapted, with permission, from Noonan MP, et al., 2014 120.


Figure 3. Example of glial‐neuron changes in the supraoptic nucleus of (A) an normal female rat with a clear astrocytic investment (as) around the neuron and (B) a lactating rat in which multiple synapses (arrows) are observed when the glial investment of the neuron is withdrawn. Adapted, with permission, from Theodosis DT, et al., 2004 151.


Figure 4. Indirect evidence for the presence of gap junctions between neurons (A and C) through detection of coupled neurons after a fluorescent dye is injected into only one of the two neurons. (B and D) Cells that appear to lack gap junction communication. Adapted, with permission, from Hatton GI and Yang QZ, 2001 56.


Figure 5. Dendrodendritic interactions in GnRH neurons. Intercellular bridges are seen between GnRH dendrites. (A) Examples of dendritic processes from a rhesus monkey whose bridges between immunoreactive GnRH neurons appear as fine ladders (Hoffman G, unpublished data). (B) Example of two intercellular bridges across GnRH neurons in a rat brain (red circle). (C) Dendritic bundling between two (arrowheads) or three dendrites (arrows) of GnRH neurons labeled with either green fluorescent protein (colored green) or injected biocytin (colored red or yellow). Adapted, with permission, from Campbell RE, et al., 2009 14.


Figure 6. Example of μ‐opiate receptor (MOR) translocation in response to estrogen treatment. (A) Ovariectomized female rat (OVX); (B) OVX rat treated with estradiol benzoate (50 μg, EB). This approach is used as evidence that a receptor ligand has affected neuronal activity. Adapted, with permission, from Eckersell CB, et al., 1998 36. Copyright 1998 Society for Neuroscience.


Figure 7. Spines on kisspeptin neurons of the arcuate nucleus are abundant in ovariectomized animals (A–C) in contrast to ovariectomized animals given estrogen replacement (D). The relationship of the spine patterns to firing dynamics of the neurons leads to the use of spine morphology as a marker of the neuron's activity. Adapted, with permission, from Cholanian M, et al., 2015 20.


Figure 8. Changes in the expression of the cytoskeletal protein, activity‐regulated cytoskeletal protein (Arc/Arg3.1), reflect changes in neuron activity. The figure shows induced ARC/Arg3.1 expression in the suprachiasmatic nucleus in response to lights on in a mouse at 0, 60, 120, 180, and 300 min after lights on. Adapted, with permission, from Nishimura M, et al., 2003 119.


Figure 9. Vasopressin mRNA in neurons of the supraoptic nucleus in a control normonatremic animal (A and B) and after 7 days of hyponatremia. Hyponatremia, a treatment that reduces firing of vasopressin neurons, reduces markedly mRNA expression in the neurons. C and D are higher magnifications of the cells. The bar graph (E) compares the mRNA levels determined from in situ hybridization to those of solution hybridization analysis for vasopressin (Exon C). Hyponatremia significantly decreased mRNA for vasopression (**p < 0.001). The magnitude of suppression with the two detection methods was similar. Adapted, with permission, from Hoffman G, et al., 1995 63.


Figure 10. Tyrosine hydroxylase (TH) RNA levels in continuously suckling rats (0 h) and at 1.5, 6, 12, and 24 h after pup removal reveal initial nuclear sites (heteronuclear RNA) in the first hours after pup removal, and then gradual reexpression of mature mRNA in the cell cytoplasm to levels seen in cycling rats at the later times. Adapted, with permission, from Berghorn KA, et al., 2001 6.


Figure 11. Staining of the protein prohormone for vasopressin and oxytocin is low under baseline conditions (A), but after hypernatremia (B) is strikingly elevated in the supraoptic nucleus. Adapted, with permission, from Verbalis JG, et al., 1991 155.


Figure 12. Examples of the use of promoter‐driven flag expression. a) Example of use of the vasopressin promoter to drive expression of green fluorescent protein (GFP) to enable detection of changes in vasopressin's synthetic activity in chronically salt‐loaded rats. Compared to controls (A–C), expression of the GFP in the SON, PVN, and internal zone of the median eminence of salt‐loaded rats is strikingly elevated (D–F). Adapted, with permission, from Suzuki H, et al., 2009 146. b) Changes in a flag linked to the activity‐depended cytoskeletal protein ARC in the parvocellular PVN (circle) in a control rat (A), a rat exposed to an acute restraint stress (B), or a rat exposed to repeated restraint stress (C). (D) A rat exposed to an immune challenge (lipopolysaccharide, LPS) 3 h earlier. (E) An LPS animal after 6 h. (F) An animal stimulated by both repeated restraint and LPS. (G) A higher magnification of (F) revealing the GFP flag for ARC. (H) Labeling of the same section for CRH. (I) The double labeling of ARC (green) and CRH. Adapted, with permission, from Grinevich V, et al., 2009 53.


Figure 13. Aberrant expression of surrogate proteins. The fact that all cells of the body have the same DNA can result in expression of a surrogate protein in cells that would normally not express that protein. The likely explanation for this is that the insertion of a transgene under a defined promoter lacks sequences that would normally suppress the protein. The figure illustrates examples of aberrant expression of GnRH‐directed green fluorescent protein in populations of neurons that normally would not express GnRH in the lateral hypothalamus (A, black box) and in the dorsal septal area (B, white box). Hoffman G, unpublished data.


Figure 14. Direct assay of mRNA expression. (A) Striking changes in the mRNA for tyrosine hydroxylase detected by radioactive in situ hybridization technology in cycling, lactating rats, and lactating rats whose pups were removed for 24 h. Reused, with permission, from Wang HJ, et al., 1993 158. That neural activity determines the suppression of TH mRNA during suckling in the arcuate nucleus is illustrated after blocking nipples on only one side of the body as illustrated in B. In C, TH mRNA is upregulated back to baseline levels in the arcuate nucleus only on the side contralateral to the nipple blockade. Like other somatosensory paths to the thalamus, the course from the nipples to the thalamus also crosses. Reused, with permission, from Berghorn KA, et al., 2001 6.


Figure 15. Example of a dose‐response in the induction of Fos (left figures) in oxytocin neurons (right figures) after graded treatment with cholecystokinin. Reused, with permission, from Verbalis JG, et al., 1991 156.


Figure 16. Example of the monitoring of fluorescent Ca++ sensitive dyes in electrically stimulated suprachiasmatic nucleus neurons from slice preparations. Reused, with permission, from Irwin RP and Allen CN, 2013 73.


Figure 17. Example of the induction of galanin (black) in GnRH neurons following a surge in the GnRH system. Interestingly, the GnRH in the neurons (brown) is not markedly changed. Hoffman G, unpublished data. Activity dependence of this phenomenon is seen when the GnRH system's surge is delayed for 24 h and delays the galanin expression.


Figure 18. Examples of the changes in CRH hnRNA and that of vasopressin in neurons of the parvocellular PVN after a single or repeated restraint stress. The upper panels (A–D) present CRH hnRNA, and the lower panels (E–H) vasopressin hnRNA. (A) control naïve rat, (B) single restraint, (C) basal CRH expression before repeated restraint, and (D) CRH hnRNA after 14 restraint episodes. Note that CRH hnRNA is elevated by acute restraint but is suppressed after repeated stress (either before or after the last restraint). (E) The expression of vasopressin hnRNA is low in the parvocellular PVN (MP) of naïve rats. However, after a single or multiple episodes of restraint, the vasopressin hnRNA is elevated (F–H). Reused, with permission, from Aguilera G, et al., 2008 1.


Figure 19. Effective use of timing differences in expression of hnRNA versus cytoplasmic mRNA for tyrosine hydroxylase following administration of a glutamate agonist. (A) Control; (B) 1 h after delivery of NMDA. Hoffman G, unpublished data.
References
 1.Aguilera G, Subburaju S, Young S, Chen J. The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress. Prog Brain Res 170: 29‐39, 2008.
 2.Amico JA, Crowley RS, Insel TR, Thomas A, O'Keefe JA. Effect of gonadal steroids upon hypothalamic oxytocin expression. Adv Exp Med Biol 395: 23‐35, 1995.
 3.Appelbaum L, Wang G, Yokogawa T, Skariah GM, Smith SJ, Mourrain P, Mignot E. Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron 68: 87‐98, 2010.
 4.Arima H, Kondo K, Kakiya S, Nagasaki H, Yokoi H, Yambe Y, Murase T, Iwasaki Y, Oiso Y. Rapid and sensitive vasopressin heteronuclear RNA responses to changes in plasma osmolality. J Neuroendocrinol 11: 337‐341, 1999.
 5.Aumann TD, Egan K, Lim J, Boon WC, Bye CR, Chua HK, Baban N, Parish CL, Bobrovskaya L, Dickson P, Horne MK. Neuronal activity regulates expression of tyrosine hydroxylase in adult mouse substantia nigra pars compacta neurons. J Neurochem 116: 646‐658, 2011.
 6.Berghorn KA, Le WW, Sherman TG, Hoffman GE. Suckling stimulus suppresses messenger RNA for tyrosine hydroxylase in arcuate neurons during lactation. J Comp Neurol 438: 423‐432, 2001.
 7.Brady LS, Lynn AB, Glowa JR, Le DQ, Herkenham M. Repeated electroconvulsive shock produces long‐lasting increases in messenger RNA expression of corticotropin‐releasing hormone and tyrosine hydroxylase in rat brain. Therapeutic implications. J Clin Invest 94: 1263‐1268, 1994.
 8.Briggs DI, Lockie SH, Benzler J, Wu Q, Stark R, Reichenbach A, Hoy AJ, Lemus MB, Coleman HA, Parkington HC, Tups A, Andrews ZB. Evidence that diet‐induced hyperleptinemia, but not hypothalamic gliosis, causes ghrelin resistance in NPY/AgRP neurons of male mice. Endocrinology 155: 2411‐2422, 2014.
 9.Brown RS, Kokay IC, Phillipps HR, Yip SH, Gustafson P, Wyatt A, Larsen CM, Knowles P, Ladyman SR, LeTissier P, Grattan DR. Conditional deletion of the prolactin receptor reveals functional subpopulations of dopamine neurons in the arcuate nucleus of the hypothalamus. J Neurosci 36: 9173‐9185, 2016.
 10.Brown RSE, Aoki M, Ladyman SR, Phillipps HR, Wyatt A, Boehm U, Grattan DR. Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior. Proc Natl Acad Sci U S A 114: 10779‐10784, 2017.
 11.Burke SM, Cohen‐Kettenis PT, Veltman DJ, Klink DT, Bakker J. Hypothalamic response to the chemo‐signal androstadienone in gender dysphoric children and adolescents. Front Endocrinol 5: 60, 2014.
 12.Calizo LH, Flanagan‐Cato LM. Estrogen selectively regulates spine density within the dendritic arbor of rat ventromedial hypothalamic neurons. J Neurosci 20: 1589‐1596, 2000.
 13.Calza L, Giardino L, Hokfelt T. Galanin upregulation in glial cells after colchicine injection is dependent on thyroid hormone. Ann N Y Acad Sci 863: 417‐420, 1998.
 14.Campbell RE, Gaidamaka G, Han SK, Herbison AE. Dendro‐dendritic bundling and shared synapses between gonadotropin‐releasing hormone neurons. Proc Natl Acad Sci U S A 106: 10835‐10840, 2009.
 15.Campbell RE, Han SK, Herbison AE. Biocytin filling of adult gonadotropin‐releasing hormone neurons in situ reveals extensive, spiny, dendritic processes. Endocrinology 146: 1163‐1169, 2005.
 16.Carlson DE, Le W, Chiu WC, Hoffman GE. Messenger RNA for neuropeptide Y in the arcuate nucleus increases in parallel with plasma adrenocorticotropin during sepsis in the rat. Neurosci Lett 452: 146‐150, 2009.
 17.Chan RK, Brown ER, Ericsson A, Kovacs KJ, Sawchenko PE. A comparison of two immediate‐early genes, c‐fos and NGFI‐B, as markers for functional activation in stress‐related neuroendocrine circuitry. J Neurosci 13: 5126‐5138, 1993.
 18.Cho J, Min N, Franzen L, Baker H. Rapid down‐regulation of tyrosine hydroxylase expression in the olfactory bulb of naris‐occluded adult rats. J Comp Neurol 369: 264‐276, 1996.
 19.Cholanian M, Krajewski‐Hall SJ, Levine RB, McMullen NT, Rance NE. Electrophysiology of arcuate neurokinin B neurons in female Tac2‐EGFP transgenic mice. Endocrinology 155: 2555‐2565, 2014.
 20.Cholanian M, Krajewski‐Hall SJ, McMullen NT, Rance NE. Oestradiol reduces the dendritic spine density of KNDy neurones in the arcuate nucleus of ovariectomized Tac2‐EGFP transgenic mice. J Neuroendocrinol, 2015.
 21.Christensen A, Dewing P, Micevych P. Immediate early gene activity‐regulated cytoskeletal‐associated protein regulates estradiol‐induced lordosis behavior in female rats. J Neurosci Res 93: 67‐74, 2015.
 22.Cobbett P, Yang QZ, Hatton GI. Incidence of dye coupling among magnocellular paraventricular nucleus neurons in male rats is testosterone dependent. Brain Res Bull 18: 365‐370, 1987.
 23.Coolen LM, Fitzgerald ME, Yu L, Lehman MN. Activation of mu opioid receptors in the medial preoptic area following copulation in male rats. Neuroscience 124: 11‐21, 2004.
 24.Cortes R, Ceccatelli S, Schalling M, Hokfelt T. Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: An in situ hybridization study. Synapse 6: 369‐391, 1990.
 25.Craner SL, Hoffman GE, Lund JS, Humphrey AL, Lund RD. cFos labeling in rat superior colliculus: Activation by normal retinal pathways and pathways from intracranial retinal transplants. Exp Neurol 117: 219‐229, 1992.
 26.Darling RD, Alzghoul L, Zhang J, Khatri N, Paul IA, Simpson KL, Lin RC. Perinatal citalopram exposure selectively increases locus ceruleus circuit function in male rats. J Neurosci 31: 16709‐16715, 2011.
 27.Dauvilliers Y, Comte F, Bayard S, Carlander B, Zanca M, Touchon J. A brain PET study in patients with narcolepsy‐cataplexy. J Neurol Neurosurg Psychiatry 81: 344‐348, 2010.
 28.de Croft S, Boehm U, Herbison AE. Neurokinin B activates arcuate kisspeptin neurons through multiple tachykinin receptors in the male mouse. Endocrinology 154: 2750‐2760, 2013.
 29.de Croft S, Piet R, Mayer C, Mai O, Boehm U, Herbison AE. Spontaneous kisspeptin neuron firing in the adult mouse reveals marked sex and brain region differences but no support for a direct role in negative feedback. Endocrinology 153: 5384‐5393, 2012.
 30.Dhillon H, Dunn AM, Esquivel E, Hamernik DL, Wise ME. The estradiol‐induced luteinizing hormone surge in the ewe is not associated with increased gonadotropin‐releasing hormone messenger ribonucleic acid levels. Biol Reprod 57: 107‐111, 1997.
 31.Dimitrov E, Usdin TB. Tuberoinfundibular peptide of 39 residues modulates the mouse hypothalamic‐pituitary‐adrenal axis via paraventricular glutamatergic neurons. J Comp Neurol 518: 4375‐4394, 2010.
 32.Dimitrov EL, Yanagawa Y, Usdin TB. Forebrain GABAergic projections to locus coeruleus in mouse. J Comp Neurol 521: 2373‐2397, 2013.
 33.Douglas AJ, Meeren HK, Johnstone LE, Pfaff DW, Russell JA, Brooks PJ. Stimulation of expression of the oxytocin gene in rat supraoptic neurons at parturition. Brain Res 782: 167‐174, 1998.
 34.Dragunow M, Beilharz E, Sirimanne E, Lawlor P, Williams C, Bravo R, Gluckman P. Immediate‐early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic‐ischaemic injury to the young rat brain. Brain Res Mol Brain Res 25: 19‐33, 1994.
 35.Duelli R, Kuschinsky W. Brain glucose transporters: Relationship to local energy demand. News Physiol Sci 16: 71‐76, 2001.
 36.Eckersell CB, Popper P, Micevych PE. Estrogen‐induced alteration of mu‐opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala. J Neurosci 18: 3967‐3976, 1998.
 37.Engstrom M, Hallbook T, Szakacs A, Karlsson T, Landtblom AM. Functional magnetic resonance imaging in narcolepsy and the kleine‐levin syndrome. Front Neurol 5: 105, 2014.
 38.Eriksson M, Ceccatelli S, Uvnas‐Moberg K, Iadarola M, Hokfelt T. Expression of Fos‐related antigens, oxytocin, dynorphin and galanin in the paraventricular and supraoptic nuclei of lactating rats. Neuroendocrinology 63: 356‐367, 1996.
 39.Fenelon VS, Poulain DA, Theodosis DT. Oxytocin neuronal activation and Fos expression: A quantitative immunocytochemical analysis of the effect of lactation, parturition, osmotic and cardiovascular stimulation. Neuroscience 53: 77‐89, 1993.
 40.Finn PD, Steiner RA, Clifton DK. Temporal patterns of gonadotropin‐releasing hormone (GnRH), c‐fos, and galanin gene expression in GnRH neurons relative to the luteinizing hormone surge in the rat. J Neurosci 18: 713‐719, 1998.
 41.Flanagan‐Cato LM, Calizo LH, Griffin GD, Lee BJ, Whisner SY. Sexual behaviour induces the expression of activity‐regulated cytoskeletal protein and modifies neuronal morphology in the female rat ventromedial hypothalamus. J Neuroendocrinol 18: 857‐864, 2006.
 42.Flood DG, Gibbs FP. Species difference in circadian [14C]2‐deoxyglucose uptake by suprachiasmatic nuclei. Brain Res 232: 200‐205, 1982.
 43.Fujihara H, Ueta Y, Suzuki H, Katoh A, Ohbuchi T, Otsubo H, Dayanithi G, Murphy D. Robust up‐regulation of nuclear red fluorescent‐tagged fos marks neuronal activation in green fluorescent vasopressin neurons after osmotic stimulation in a double‐transgenic rat. Endocrinology 150: 5633‐5638, 2009.
 44.Fujii R, Ichikawa M, Ozaki M. Imaging of molecular dynamics regulated by electrical activities in neural circuits and in synapses. Neurosignals 16: 260‐277, 2008.
 45.Fujio T, Fujihara H, Shibata M, Yamada S, Onaka T, Tanaka K, Morita H, Dayanithi G, Kawata M, Murphy D, Ueta Y. Exaggerated response of arginine vasopressin‐enhanced green fluorescent protein fusion gene to salt loading without disturbance of body fluid homeostasis in rats. J Neuroendocrinol 18: 776‐785, 2006.
 46.Fujioka H, Suzuki M, Yamanouchi K, Ohta A, Nagashima H, Kato M, Nishihara M. Generation of transgenic rats expressing enhanced green fluorescent protein in gonadotropin‐releasing hormone neurons. J Reprod Dev 49: 523‐529, 2003.
 47.Gao XB, Ghosh PK, van den Pol AN. Neurons synthesizing melanin‐concentrating hormone identified by selective reporter gene expression after transfection in vitro: Transmitter responses. J Neurophysiol 90: 3978‐3985, 2003.
 48.Gaus SE, Strecker RE, Tate BA, Parker RA, Saper CB. Ventrolateral preoptic nucleus contains sleep‐active, galaninergic neurons in multiple mammalian species. Neuroscience 115: 285‐294, 2002.
 49.Gautron L, Lazarus M, Scott MM, Saper CB, Elmquist JK. Identifying the efferent projections of leptin‐responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach. J Comp Neurol 518: 2090‐2108, 2010.
 50.Girotti M, Weinberg MS, Spencer RL. Differential responses of hypothalamus‐pituitary‐adrenal axis immediate early genes to corticosterone and circadian drive. Endocrinology 148: 2542‐2552, 2007.
 51.Glasgow E, Murase T, Zhang B, Verbalis JG, Gainer H. Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality versus hyposmolality. Am J Physiol Regul Integr Comp Physiol 279: R1239‐R1250, 2000.
 52.Gore AC, Roberts JL. Regulation of gonadotropin‐releasing hormone gene expression in vivo and in vitro. Front Neuroendocrinol 18: 209‐245, 1997.
 53.Grinevich V, Kolleker A, Eliava M, Takada N, Takuma H, Fukazawa Y, Shigemoto R, Kuhl D, Waters J, Seeburg PH, Osten P. Fluorescent Arc/Arg3.1 indicator mice: A versatile tool to study brain activity changes in vitro and in vivo. J Neurosci Methods 184: 25‐36, 2009.
 54.Gu G, Rojo AA, Zee MC, Yu J, Simerly RB. Hormonal regulation of CREB phosphorylation in the anteroventral periventricular nucleus. J Neurosci 16: 3035‐3044, 1996.
 55.Hatton GI, Yang QZ. Incidence of neuronal coupling in supraoptic nuclei of virgin and lactating rats: Estimation by neurobiotin and lucifer yellow. Brain Res 650: 63‐69, 1994.
 56.Hatton GI, Yang QZ. Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling. J Neurosci 21: 2974‐2982, 2001.
 57.Hatton GI, Yang QZ, Cobbett P. Dye coupling among immunocytochemically identified neurons in the supraoptic nucleus: Increased incidence in lactating rats. Neuroscience 21: 923‐930, 1987.
 58.Hatton GI, Zhao Yang Q. Peripartum interneuronal coupling in the supraoptic nucleus. Brain Res 932: 120‐123, 2002.
 59.Herbison AE, de Tassigny X, Doran J, Colledge WH. Distribution and postnatal development of Gpr54 gene expression in mouse brain and gonadotropin‐releasing hormone neurons. Endocrinology 151: 312‐321, 2010.
 60.Herman JP, Schafer MK, Thompson RC, Watson SJ. Rapid regulation of corticotropin‐releasing hormone gene transcription in vivo. Mol Endocrinol 6: 1061‐1069, 1992.
 61.Herman JP, Schafer MK, Watson SJ, Sherman TG. In situ hybridization analysis of arginine vasopressin gene transcription using intron‐specific probes. Mol Endocrinol 5: 1447‐1456, 1991.
 62.Hermanstyne TO, Subedi K, Le WW, Hoffman GE, Meredith AL, Mong JA, Misonou H. Kv2.2: A novel molecular target to study the role of basal forebrain GABAergic neurons in the sleep‐wake cycle. Sleep 36: 1839‐1848, 2013.
 63.Hoffman G, Berghorn K, Knapp L, Le W, Sherman T. Physiological stimulation of vasopressin and oxytocin neurons: Perspectives from Fos activation. In: Saito T, Kurokawa K, Yoshida S, editors. Neurohypophysis: Recent Progress of Vasopressin and Oxytocin Research. Amsterdam: Elsevier, 1995, p. 151‐164.
 64.Hoffman G, Murphy A. Anatomical markers of activity in hypothalamic systems. In: Conn P, Freeman M, editors. Neuroendocrinology in Physiology and Medicine. Totowa, NJ: Humana Press, 1999, p. 541‐552.
 65.Hoffman GE, Le WW, Abbud R, Lee WS, Smith MS. Use of Fos‐related antigens (FRAs) as markers of neuronal activity: FRA changes in dopamine neurons during proestrus, pregnancy and lactation. Brain Res 654: 207‐215, 1994.
 66.Hoffman GE, Le WW, Schulterbrandt T, Legan SJ. Estrogen and progesterone do not activate Fos in AVPV or LHRH neurons in male rats. Brain Res 1054: 116‐124, 2005.
 67.Hoffman GE, Lee W‐S, Smith MS, Abbud R, Roberts MM, Robinson AG, Verbalis JG. cFos and Fos related antigens as markers for neuronal activity: Perspectives from neuroendocrine systems. In: Grzanna R, Brown RM editors. National Institute on Drug Abuse (NIDA) Technical Review Activation of Immediate Early Genes by Drugs of Abuse. Rockville, MD: Neuroscience Research Branch National Institute on Drug Abuse, 1992, p. 117‐133.
 68.Hoffman GE, Lyo D. Anatomical markers of activity in neuroendocrine systems: Are we all ‘fos‐ed out’? J Neuroendocrinol 14: 259‐268, 2002.
 69.Hong JH, Min CH, Jeong B, Kojiya T, Morioka E, Nagai T, Ikeda M, Lee KJ. Intracellular calcium spikes in rat suprachiasmatic nucleus neurons induced by BAPTA‐based calcium dyes. PLoS One 5: e9634, 2010.
 70.Hosny S, Jennes L. Identification of gap junctional connexin‐32 mRNA and protein in gonadotropin‐releasing hormone neurons of the female rat. Neuroendocrinology 67: 101‐108, 1998.
 71.Hu L, Olson AJ, Weiner RI, Goldsmith PC. Connexin 26 expression and extensive gap junctional coupling in cultures of GT1‐7 cells secreting gonadotropin‐releasing hormone. Neuroendocrinology 70: 221‐227, 1999.
 72.Huh J, Park K, Hwang IS, Jung SI, Kim HJ, Chung TW, Jeong GW. Brain activation areas of sexual arousal with olfactory stimulation in men: A preliminary study using functional MRI. J Sex Med 5: 619‐625, 2008.
 73.Irwin RP, Allen CN. Simultaneous electrophysiological recording and calcium imaging of suprachiasmatic nucleus neurons. J Vis Exp 82: 50794, 2013.
 74.Itoi K, Talukder AH, Fuse T, Kaneko T, Ozawa R, Sato T, Sugaya T, Uchida K, Yamazaki M, Abe M, Natsume R, Sakimura K. Visualization of corticotropin‐releasing factor neurons by fluorescent proteins in the mouse brain and characterization of labeled neurons in the paraventricular nucleus of the hypothalamus. Endocrinology 155: 4054‐4060, 2014.
 75.Jarvie BC, Hentges ST. Expression of GABAergic and glutamatergic phenotypic markers in hypothalamic proopiomelanocortin neurons. J Comp Neurol 520: 3863‐3876, 2012.
 76.Jensen D, Zhang Z, Flynn FW. Trafficking of tachykinin neurokinin 3 receptor to nuclei of neurons in the paraventricular nucleus of the hypothalamus following osmotic challenge. Neuroscience 155: 308‐316, 2008.
 77.Jones EG, Hartman BK. Recent advances in neuroanatomical methodology. Annu Rev Neurosci 1: 215‐296, 1978.
 78.Joo EY, Hong SB, Tae WS, Kim JH, Han SJ, Cho YW, Yoon CH, Lee SI, Lee MH, Lee KH, Kim MH, Kim BT, Kim L. Cerebral perfusion abnormality in narcolepsy with cataplexy. Neuroimage 28: 410‐416, 2005.
 79.Junier MP, Wolff A, Hoffman GE, Ma YJ, Ojeda SR. Effect of hypothalamic lesions that induce precocious puberty on the morphological and functional maturation of the luteinizing hormone‐releasing hormone neuronal system. Endocrinology 131: 787‐798, 1992.
 80.Kawasaki M, Ponzio TA, Yue C, Fields RL, Gainer H. Neurotransmitter regulation of c‐fos and vasopressin gene expression in the rat supraoptic nucleus. Exp Neurol 219: 212‐222, 2009.
 81.Kim GW, Jeong GW. A comparative study of brain activation patterns associated with sexual arousal between males and females using 3.0‐T functional magnetic resonance imaging. Sex Health 11: 11‐16, 2014.
 82.Klein DC, Moore RY, Reppert SM, editors. Suprachiasmatic Nucleus: The Mind's Clock. New York, NY: Oxford University Press, 1991, p. 467.
 83.Koban M, Le WW, Hoffman GE. Changes in hypothalamic corticotropin‐releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats. Endocrinology 147: 421‐431, 2006.
 84.Lafarga M, Berciano MT, Garcia‐Segura LM, Andres MA, Carmo‐Fonseca M. Acute osmotic/stress stimuli induce a transient decrease of transcriptional activity in the neurosecretory neurons of supraoptic nuclei. J Neurocytol 27: 205‐217, 1998.
 85.Lafarga M, Berciano MT, Martinez‐Guijarro FJ, Andres MA, Mellstrom B, Lopez‐Garcia C, Naranjo JR. Fos‐like expression and nuclear size in osmotically stimulated supraoptic nucleus neurons. Neuroscience 50: 867‐875, 1992.
 86.Lafarga M, Martinez‐Guijarro FJ, Berciano MT, Blasco‐Ibanez JM, Andres MA, Mellstrom B, Lopez‐Garcia C, Naranjo JR. Nuclear Fos domains in transcriptionally activated supraoptic nucleus neurons. Neuroscience 57: 353‐364, 1993.
 87.Lahti KM, Ferris CF, Li F, Sotak CH, King JA. Imaging brain activity in conscious animals using functional MRI. J Neurosci Methods 82: 75‐83, 1998.
 88.Le WW, Berghorn KA, Rassnick S, Hoffman GE. Periventricular preoptic area neurons coactivated with luteinizing hormone (LH)‐releasing hormone (LHRH) neurons at the time of the LH surge are LHRH afferents. Endocrinology 140: 510‐519, 1999.
 89.Le WW, Berghorn KA, Smith MS, Hoffman GE. Alpha1‐adrenergic receptor blockade blocks LH secretion but not LHRH cFos activation. Brain Res 747: 236‐245, 1997.
 90.Leak RK, Card JP, Moore RY. Suprachiasmatic pacemaker organization analyzed by viral transynaptic transport. Brain Res 819: 23‐32, 1999.
 91.Lee WS, Smith MS, Hoffman GE. Progesterone enhances the surge of luteinizing hormone by increasing the activation of luteinizing hormone‐releasing hormone neurons. Endocrinology 127: 2604‐2606, 1990.
 92.Lee WS, Smith MS, Hoffman GE. cFos activity identifies recruitment of LHRH neurons during the ascending phase of the proestrous luteinizing hormone surge. J Neuroendocrinol 4: 161‐166, 1992.
 93.Legradi G, Holzer D, Kapcala LP, Lechan RM. Glucocorticoids inhibit stress‐induced phosphorylation of CREB in corticotropin‐releasing hormone neurons of the hypothalamic paraventricular nucleus. Neuroendocrinology 66: 86‐97, 1997.
 94.Leng G, Dyball RE, Way SA. Naloxone potentiates the release of oxytocin induced by systemic administration of cholecystokinin without enhancing the electrical activity of supraoptic oxytocin neurones. Exp Brain Res 88: 321‐325, 1992.
 95.Levine JE, Ramirez VD. In vivo release of luteinizing hormone‐releasing hormone estimated with push‐pull cannulae from the mediobasal hypothalami of ovariectomized, steroid‐primed rats. Endocrinology 107: 1782‐1790, 1980.
 96.Li Y, Pehrson AL, Waller JA, Dale E, Sanchez C, Gulinello M. A critical evaluation of the activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1)'s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression. Front Neurosci 9: 279, 2015.
 97.Logothetis NK. The neural basis of the blood‐oxygen‐level‐dependent functional magnetic resonance imaging signal. Philos Trans R Soc Lond B Biol Sci 357: 1003‐1037, 2002.
 98.Lozic M, Greenwood M, Sarenac O, Martin A, Hindmarch C, Tasic T, Paton J, Murphy D, Japundzic‐Zigon N. Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats. Br J Pharmacol 171: 4385‐4398, 2014.
 99.Luckman SM, Dyball RE, Leng G. Induction of c‐fos expression in hypothalamic magnocellular neurons requires synaptic activation and not simply increased spike activity. J Neurosci 14: 4825‐4830, 1994.
 100.Ly HG, Ceccarini J, Weltens N, Bormans G, Van Laere K, Tack J, Van Oudenhove L. Increased cerebral cannabinoid‐1 receptor availability is a stable feature of functional dyspepsia: A [F]MK‐9470 PET study. Psychother Psychosom 84: 149‐158, 2015.
 101.Ma XM, Levy A, Lightman SL. Rapid changes in heteronuclear RNA for corticotrophin‐releasing hormone and arginine vasopressin in response to acute stress. J Endocrinol 152: 81‐89, 1997.
 102.Magis D, Bruno MA, Fumal A, Gerardy PY, Hustinx R, Laureys S, Schoenen J. Central modulation in cluster headache patients treated with occipital nerve stimulation: An FDG‐PET study. BMC Neurol 11: 25, 2011.
 103.Mani BK, Walker AK, Lopez Soto EJ, Raingo J, Lee CE, Perello M, Andrews ZB, Zigman JM. Neuroanatomical characterization of a growth hormone secretagogue receptor‐green fluorescent protein reporter mouse. J Comp Neurol 522: 3644‐3666, 2014.
 104.Mar L, Yang FC, Ma Q. Genetic marking and characterization of Tac2‐expressing neurons in the central and peripheral nervous system. Mol Brain 5: 3, 2012.
 105.Marks DL, Smith MS, Vrontakis M, Clifton DK, Steiner RA. Regulation of galanin gene expression in gonadotropin‐releasing hormone neurons during the estrous cycle of the rat. Endocrinology 132: 1836‐1844, 1993.
 106.Maurer JA, Wray S. Luteinizing hormone‐releasing hormone (LHRH) neurons maintained in hypothalamic slice explant cultures exhibit a rapid LHRH mRNA turnover rate. J Neurosci 17: 9481‐9491, 1997.
 107.McKenna JT, Yang C, Franciosi S, Winston S, Abarr KK, Rigby MS, Yanagawa Y, McCarley RW, Brown RE. Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse. J Comp Neurol 521: 1225‐1250, 2013.
 108.Merchenthaler I. Induction of enkephalin in tuberoinfundibular dopaminergic neurons during lactation. Endocrinology 133: 2645‐2651, 1993.
 109.Merchenthaler I. Induction of enkephalin in tuberoinfundibular dopaminergic neurons of pregnant, pseudopregnant, lactating and aged female rats. Neuroendocrinology 60: 185‐193, 1994.
 110.Micevych PE, Popper P, Hatton GI. Connexin 32 mRNA levels in the rat supraoptic nucleus: Up‐regulation prior to parturition and during lactation. Neuroendocrinology 63: 39‐45, 1996.
 111.Michopoulos V, Embree M, Reding K, Sanchez MM, Toufexis D, Votaw JR, Voll RJ, Goodman MM, Rivier J, Wilson ME, Berga SL. CRH receptor antagonism reverses the effect of social subordination upon central GABAA receptor binding in estradiol‐treated ovariectomized female rhesus monkeys. Neuroscience 250: 300‐308, 2013.
 112.Miklos Z, Flynn FW, Lessard A. Stress‐induced dendritic internalization and nuclear translocation of the neurokinin‐3 (NK3) receptor in vasopressinergic profiles of the rat paraventricular nucleus of the hypothalamus. Brain Res 1590: 31‐44, 2014.
 113.Miller B, Marks LA, Koller JM, Newman BJ, Bretthorst GL, Black KJ. Prolactin and fMRI response to SKF38393 in the baboon. PeerJ 1: e195, 2013.
 114.Mills RH, Sohn RK, Micevych PE. Estrogen‐induced mu‐opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y‐Y1 receptor activation in the arcuate nucleus of female rats. J Neurosci 24: 947‐955, 2004.
 115.Moenter SM, Karsch FJ, Lehman MN. Fos expression during the estradiol‐induced gonadotropin‐releasing hormone (GnRH) surge of the ewe: Induction in GnRH and other neurons. Endocrinology 133: 896‐903, 1993.
 116.Moga MM, Moore RY. Organization of neural inputs to the suprachiasmatic nucleus in the rat. J Comp Neurol 389: 508‐534, 1997.
 117.Morgan JI, Cohen DR, Hempstead JL, Curran T. Mapping patterns of c‐fos expression in the central nervous system after seizure. Science 237: 192‐197, 1987.
 118.Newman GC, Hospod FE, Patlak CS, Moore RY. Analysis of in vitro glucose utilization in a circadian pacemaker model. J Neurosci 12: 2015‐2021, 1992.
 119.Nishimura M, Yamagata K, Sugiura H, Okamura H. The activity‐regulated cytoskeleton‐associated (Arc) gene is a new light‐inducible early gene in the mouse suprachiasmatic nucleus. Neuroscience 116: 1141‐1147, 2003.
 120.Noonan MP, Sallet J, Mars RB, Neubert FX, O'Reilly JX, Andersson JL, Mitchell AS, Bell AH, Miller KL, Rushworth MF. A neural circuit covarying with social hierarchy in macaques. PLoS Biol 12: e1001940, 2014.
 121.Novaira HJ, Ng Y, Wolfe A, Radovick S. Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting neuronal cell lines. Mol Cell Endocrinol 311: 126‐134, 2009.
 122.Novaira HJ, Sonko ML, Hoffman G, Koo Y, Ko C, Wolfe A, Radovick S. Disrupted kisspeptin signaling in GnRH neurons leads to hypogonadotrophic hypogonadism. Mol Endocrinol 28: 225‐238, 2014.
 123.Oh SK, Kim GW, Yang JC, Kim SK, Kang HK, Jeong GW. Brain activation in response to visually evoked sexual arousal in male‐to‐female transsexuals: 3.0 tesla functional magnetic resonance imaging. Korean J Radiol 13: 257‐264, 2012.
 124.Oliet SH, Panatier A, Piet R, Mothet JP, Poulain DA, Theodosis DT. Neuron‐glia interactions in the rat supraoptic nucleus. Prog Brain Res 170: 109‐117, 2008.
 125.O'Neil RG, Wu L, Mullani N. Uptake of a fluorescent deoxyglucose analog (2‐NBDG) in tumor cells. Mol Imaging Biol 7: 388‐392, 2005.
 126.Porkka‐Heiskanen T, Smith SE, Taira T, Urban JH, Levine JE, Turek FW, Stenberg D. Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep. Am J Physiol 268: R1456‐R1463, 1995.
 127.Porteous R, Petersen SL, Yeo SH, Bhattarai JP, Ciofi P, de Tassigny XD, Colledge WH, Caraty A, Herbison AE. Kisspeptin neurons co‐express met‐enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus. J Comp Neurol 519: 3456‐3469, 2011.
 128.Poulain DA, Wakerley JB. Electrophysiology of hypothalamic magnocellular neurones secreting oxytocin and vasopressin. Neuroscience 7: 773‐808, 1982.
 129.Prevot V, Dehouck B, Poulain P, Beauvillain JC, Buee‐Scherrer V, Bouret S. Neuronal‐glial‐endothelial interactions and cell plasticity in the postnatal hypothalamus: Implications for the neuroendocrine control of reproduction. Psychoneuroendocrinology 32 (Suppl 1): S46‐S51, 2007.
 130.Roberts JL, Dutlow CM, Jakubowski M, Blum M, Millar RP. Estradiol stimulates preoptic area‐anterior hypothalamic proGnRH‐GAP gene expression in ovariectomized rats. Brain Res Mol Brain Res 6: 127‐134, 1989.
 131.Roberts MM, Robinson AG, Fitzsimmons MD, Grant F, Lee WS, Hoffman GE. c‐fos expression in vasopressin and oxytocin neurons reveals functional heterogeneity within magnocellular neurons. Neuroendocrinology 57: 388‐400, 1993.
 132.Robinson AG, Roberts MM, Evron WA, Verbalis JG, Sherman TG. Hyponatremia in rats induces downregulation of vasopressin synthesis. J Clin Invest 86: 1023‐1029, 1990.
 133.Rochefort NL, Konnerth A. Dendritic spines: From structure to in vivo function. EMBO Rep 13: 699‐708, 2012.
 134.Root DH, Mejias‐Aponte CA, Zhang S, Wang HL, Hoffman AF, Lupica CR, Morales M. Single rodent mesohabenular axons release glutamate and GABA. Nat Neurosci 17: 1543‐1551, 2014.
 135.Rossmanith WG, Marks DL, Steiner RA, Clifton DK. Inhibition of steroid‐induced galanin mRNA expression in GnRH neurons by specific NMDA‐receptor blockade. J Neuroendocrinol 8: 179‐184, 1996.
 136.Schwartz WJ. Different in vivo metabolic activities of suprachiasmatic nuclei of Turkish and golden hamsters. Am J Physiol 259: R1083‐R1085, 1990.
 137.Shiromani PJ, Magner M, Winston S, Charness ME. Time course of phosphorylated CREB and Fos‐like immunoreactivity in the hypothalamic supraoptic nucleus after salt loading. Brain Res Mol Brain Res 29: 163‐171, 1995.
 138.Sohn JW. Network of hypothalamic neurons that control appetite. BMB Rep 48 (4): 229‐233, 2015.
 139.Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: Theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897‐916, 1977.
 140.Spergel DJ, Kruth U, Shimshek DR, Sprengel R, Seeburg PH. Using reporter genes to label selected neuronal populations in transgenic mice for gene promoter, anatomical, and physiological studies. Prog Neurobiol 63: 673‐686, 2001.
 141.Stone DM, Grillo M, Margolis FL, Joh TH, Baker H. Differential effect of functional olfactory bulb deafferentation on tyrosine hydroxylase and glutamic acid decarboxylase messenger RNA levels in rodent juxtaglomerular neurons. J Comp Neurol 311: 223‐233, 1991.
 142.Sundaram T, Jeong GW, Kim TH, Kim GW, Baek HS, Kang HK. Time‐course analysis of the neuroanatomical correlates of sexual arousal evoked by erotic video stimuli in healthy males. Korean J Radiol 11: 278‐285, 2010.
 143.Suter KJ, O'Farrell L. Impaired episodic LH secretion in female mice with GFP in GnRH neurons. Am J Physiol Endocrinol Metab 295: E130‐E136, 2008.
 144.Suter KJ, Song WJ, Sampson TL, Wuarin JP, Saunders JT, Dudek FE, Moenter SM. Genetic targeting of green fluorescent protein to gonadotropin‐releasing hormone neurons: Characterization of whole‐cell electrophysiological properties and morphology. Endocrinology 141: 412‐419, 2000.
 145.Suter KJ, Wuarin JP, Smith BN, Dudek FE, Moenter SM. Whole‐cell recordings from preoptic/hypothalamic slices reveal burst firing in gonadotropin‐releasing hormone neurons identified with green fluorescent protein in transgenic mice. Endocrinology 141: 3731‐3736, 2000.
 146.Suzuki H, Kawasaki M, Ohnishi H, Nakamura T, Ueta Y. Regulatory mechanism of the arginine vasopressin‐enhanced green fluorescent protein fusion gene expression in acute and chronic stress. Peptides 30: 1763‐1770, 2009.
 147.Suzuki H, Kawasaki M, Ohnishi H, Otsubo H, Ohbuchi T, Katoh A, Hashimoto H, Yokoyama T, Fujihara H, Dayanithi G, Murphy D, Nakamura T, Ueta Y. Exaggerated response of a vasopressin‐enhanced green fluorescent protein transgene to nociceptive stimulation in the rat. J Neurosci 29: 13182‐13189, 2009.
 148.Suzuki H, Onaka T, Kasai M, Kawasaki M, Ohnishi H, Otsubo H, Saito T, Hashimoto H, Yokoyama T, Fujihara H, Dayanithi G, Murphy D, Nakamura T, Ueta Y. Response of arginine vasopressin‐enhanced green fluorescent protein fusion gene in the hypothalamus of adjuvant‐induced arthritic rats. J Neuroendocrinol 21: 183‐190, 2009.
 149.Szabo FK, Le WW, Snyder NS, Hoffman GE. Comparison of the temporal programs regulating tyrosine hydroxylase and enkephalin expressions in TIDA neurons of lactating rats following pup removal and then pup return. J Mol Neurosci 45: 110‐118, 2011.
 150.Terasawa E, Schanhofer WK, Keen KL, Luchansky L. Intracellular Ca(2+) oscillations in luteinizing hormone‐releasing hormone neurons derived from the embryonic olfactory placode of the rhesus monkey. J Neurosci 19: 5898‐5909, 1999.
 151.Theodosis DT, Piet R, Poulain DA, Oliet SH. Neuronal, glial and synaptic remodeling in the adult hypothalamus: Functional consequences and role of cell surface and extracellular matrix adhesion molecules. Neurochem Int 45: 491‐501, 2004.
 152.Tremblay ME, Lowery RL, Majewska AK. Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8: e1000527, 2010.
 153.Uhl GR, Zingg HH, Habener JF. Vasopressin mRNA in situ hybridization: Localization and regulation studied with oligonucleotide cDNA probes in normal and Brattleboro rat hypothalamus. Proc Natl Acad Sci U S A 82: 5555‐5559, 1985.
 154.Val‐Laillet D, Aarts E, Weber B, Ferrari M, Quaresima V, Stoeckel LE, Alonso‐Alonso M, Audette M, Malbert CH, Stice E. Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity. Neuroimage Clin 8: 1‐31, 2015.
 155.Verbalis JG, Hoffman GE, Rosenbaum LC, Nilaver G, Loh YP. Generation and characterization of an antiserum directed against neurohypophyseal prohormones. J Neuroendocrinol 3: 267‐272, 1991.
 156.Verbalis JG, Stricker EM, Robinson AG, Hoffman GE. Cholecystokinin activates cFos expression in hypothalamic oxytocin and corticotropin releasing hormone neurons. J Neuroendocrinol 3: 205‐213, 1991.
 157.Wakerley JB, Poulain DA, Brown D. Comparison of firing patterns in oxytocin‐ and vasopressin‐releasing neurones during progressive dehydration. Brain Res 148: 425‐440, 1978.
 158.Wang HJ, Hoffman GE, Smith MS. Suppressed tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic system during lactation. Endocrinology 133: 1657‐1663, 1993.
 159.Wang H‐J, Hoffman GE, Smith MS. Increased GnRH mRNA in the GnRH neurons expressing cFos during the proestrous LH surge. Endocrinology 136: 3673‐3676, 1995.
 160.Wang YF, Hatton GI. Astrocytic plasticity and patterned oxytocin neuronal activity: Dynamic interactions. J Neurosci 29: 1743‐1754, 2009.
 161.Witkin JW. Synchronized neuronal networks: The GnRH system. Microsc Res Tech 44: 11‐18, 1999.
 162.Witkin JW, Demasio K. Ultrastructural differences between smooth and thorny gonadotropin‐releasing hormone neurons. Neuroscience 34: 777‐783, 1990.
 163.Wolfe A, Divall S, Singh SP, Nikrodhanond AA, Baria AT, Le WW, Hoffman GE, Radovick S. Temporal and spatial regulation of CRE recombinase expression in gonadotrophin‐releasing hormone neurones in the mouse. J Neuroendocrinol 20: 909‐916, 2008.
 164.Wray S, Gainer H. Effect of neonatal gonadectomy on the postnatal development of LHRH cell subtypes in male and female rats. Neuroendocrinology 45: 413‐419, 1987.
 165.Wray S, Hoffman G. Postnatal morphological changes in rat LHRH neurons correlated with sexual maturation. Neuroendocrinology 43: 93‐97, 1986.
 166.Wray S, Kusano K, Gainer H. Maintenance of LHRH and oxytocin neurons in slice explants cultured in serum‐free media: Effects of tetrodotoxin on gene expression. Neuroendocrinology 54: 327‐339, 1991.
 167.Wu S, Divall S, Hoffman GE, Le WW, Wagner KU, Wolfe A. Jak2 is necessary for neuroendocrine control of female reproduction. J Neurosci 31: 184‐192, 2011.
 168.Yang JC, Park JI, Kim GW, Eun SJ, Lee MS, Han KL, Chae JH, Jeong GW. Effects of antidepressant treatment on sexual arousal in depressed women: A preliminary FMRI study. Psychiatry Investig 9: 379‐383, 2012.
 169.Yang QZ, Hatton GI. Dye coupling among supraoptic nucleus neurons without dendritic damage: Differential incidence in nursing mother and virgin rats. Brain Res Bull 19: 559‐565, 1987.
 170.Yang QZ, Hatton GI. Direct evidence for electrical coupling among rat supraoptic nucleus neurons. Brain Res 463: 47‐56, 1988.
 171.Yu G, Chen H, Zhao W, Matta SG, Sharp BM. Nicotine self‐administration differentially regulates hypothalamic corticotropin‐releasing factor and arginine vasopressin mRNAs and facilitates stress‐induced neuronal activation. J Neurosci 28: 2773‐2782, 2008.
 172.Yu X, Zecharia A, Zhang Z, Yang Q, Yustos R, Jager P, Vyssotski AL, Maywood ES, Chesham JE, Ma Y, Brickley SG, Hastings MH, Franks NP, Wisden W. Circadian factor BMAL1 in histaminergic neurons regulates sleep architecture. Curr Biol 24: 2838‐2844, 2014.
 173.Yue C, Mutsuga N, Sugimura Y, Verbalis J, Gainer H. Differential kinetics of oxytocin and vasopressin heteronuclear RNA expression in the rat supraoptic nucleus in response to chronic salt loading in vivo. J Neuroendocrinol 20: 227‐232, 2008.
 174.Yue C, Ponzio TA, Fields RL, Gainer H. Oxytocin and vasopressin gene expression and RNA splicing patterns in the rat supraoptic nucleus. Physiol Genomics 35: 231‐242, 2008.
 175.Zaninetti M, Blanchet C, Tribollet E, Bertrand D, Raggenbass M. Magnocellular neurons of the rat supraoptic nucleus are endowed with functional nicotinic acetylcholine receptors. Neuroscience 95: 319‐323, 2000.
 176.Zhu J, Xu XH, Knight GE, He C, Burnstock G, Xiang Z. A subpopulation of gonadotropin‐releasing hormone neurons in the adult mouse forebrain is gamma‐Aminobutyric acidergic. J Neurosci Res 93: 1611‐1621, 2015.
 177.Zingg HH, Lefebvre D, Almazan G. Regulation of vasopressin gene expression in rat hypothalamic neurons. Response to osmotic stimulation. J Biol Chem 261: 12956‐12959, 1986.
 178.Zingg HH, Lefebvre DL. Oxytocin and vasopressin gene expression during gestation and lactation. Brain Res 464: 1‐6, 1988.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Anatomical Markers of Activity in Hypothalamic Neurons
 

How to Cite

Gloria E. Hoffman. Anatomical Markers of Activity in Hypothalamic Neurons. Compr Physiol 2020, 10: 549-575. doi: 10.1002/cphy.c170021