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Article ; Online: Inhaling: endocannabinoids and food intake.

Maldonado-Avilés, Jaime G / Dileone, Ralph J

2014 Volume 17, Issue 3, Page(s) 336–337

MeSH term(s)	Animals ; Cannabinoid Receptor Agonists/pharmacology ; Eating/physiology ; Endocannabinoids/physiology ; Feeding Behavior/physiology ; Male ; Olfactory Pathways/physiology ; Olfactory Perception/physiology ; Receptor, Cannabinoid, CB1/metabolism ; Synaptic Transmission/physiology
Chemical Substances	Cannabinoid Receptor Agonists ; Endocannabinoids ; Receptor, Cannabinoid, CB1
Language	English
Publishing date	2014-02-26
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/nn.3653
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Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 67: Show issues

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Article ; Online: Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers.

D'Sa, Carrol / Dileone, Ralph J / Anderson, George M / Sinha, Rajita

Alcohol (Fayetteville, N.Y.)

2012 Volume 46, Issue 3, Page(s) 253–259

Abstract: Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of ... ...

Abstract	Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse.
MeSH term(s)	Adult ; Alcohol Drinking/blood ; Alcoholics ; Alcoholism/blood ; Brain-Derived Neurotrophic Factor/blood ; Female ; Humans ; Male ; Middle Aged ; Plasma/chemistry ; Serum/chemistry ; Temperance
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2012-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605912-0
ISSN	1873-6823 ; 0741-8329
ISSN (online)	1873-6823
ISSN	0741-8329
DOI	10.1016/j.alcohol.2011.12.001
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Zs.A 2011: Show issues

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Article: Optogenetic inhibition of neurons by internal light production.

Land, Benjamin B / Brayton, Catherine E / Furman, Kara E / Lapalombara, Zoe / Dileone, Ralph J

Frontiers in behavioral neuroscience

2014 Volume 8, Page(s) 108

Abstract: Optogenetics is an extremely powerful tool for selective neuronal activation/inhibition and dissection of neural circuits. However, a limitation of in vivo optogenetics is that an animal must be tethered to an optical fiber for delivery of light. Here, ... ...

Abstract	Optogenetics is an extremely powerful tool for selective neuronal activation/inhibition and dissection of neural circuits. However, a limitation of in vivo optogenetics is that an animal must be tethered to an optical fiber for delivery of light. Here, we describe a new method for in vivo, optogenetic inhibition of neural activity using an internal, animal-generated light source based on firefly luciferase. Two adeno-associated viruses encoding luciferase were tested and both produced concentration-dependent light after administration of the substrate, luciferin. Mice were co-infected with halorhodopsin- and luciferase-expressing viruses in the striatum, and luciferin administration significantly reduced Fos activity compared to control animals infected with halorhodopsin only. Recordings of neuronal activity in behaving animals confirmed that firing was greatly reduced after luciferin administration. Finally, amphetamine-induced locomotor activity was reduced in halorhodopsin/luciferase mice pre-injected with luciferin compared to controls. This demonstrates that virally encoded luciferase is able to generate sufficient light to activate halorhodopsin and suppress neural activity and change behavior. This approach could be used to generate inhibition in response to activation of specific molecular pathways.
Language	English
Publishing date	2014-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2014.00108
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Article ; Online: Role of orexin/hypocretin in dependence and addiction.

Sharf, Ruth / Sarhan, Maysa / Dileone, Ralph J

Brain research

2009 Volume 1314, Page(s) 130–138

Abstract: The orexins (or hypocretins) are hypothalamic neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In ...

Abstract	The orexins (or hypocretins) are hypothalamic neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In this review, we discuss orexin's interaction with the mesocorticolimbic reward pathway and the effects of drugs of abuse on the orexin system. We further review models of drug dependence and addiction and describe behavioral alterations that are seen when the orexin system is manipulated both pharmacologically and genetically. Based on the findings reported in the literature thus far, we posit that orexin functioning contributes to both drug reward and drug-related stress/aversive responsiveness; however, diverse anatomical substrates, and perhaps receptor specificity, contribute differentially to reward and stress components.
MeSH term(s)	Animals ; Humans ; Hypothalamic Area, Lateral/physiology ; Intracellular Signaling Peptides and Proteins/physiology ; Neural Pathways/drug effects ; Neural Pathways/physiology ; Neuropeptides/physiology ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/physiology ; Orexins ; Reward ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology ; Substance Withdrawal Syndrome/metabolism ; Substance Withdrawal Syndrome/physiopathology ; Substance-Related Disorders/metabolism ; Substance-Related Disorders/physiopathology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/physiology
Chemical Substances	Intracellular Signaling Peptides and Proteins ; Neuropeptides ; Orexins
Language	English
Publishing date	2009-08-20
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2009.08.028
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Zs.A 161: Show issues

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Article ; Online: GABAergic and glutamatergic efferents of the mouse ventral tegmental area.

Taylor, Seth R / Badurek, Sylvia / Dileone, Ralph J / Nashmi, Raad / Minichiello, Liliana / Picciotto, Marina R

The Journal of comparative neurology

2014 Volume 522, Issue 14, Page(s) 3308–3334

Abstract: The role of dopaminergic (DA) projections from the ventral tegmental area (VTA) in appetitive and rewarding behavior has been widely studied, but the VTA also has documented DA-independent functions. Several drugs of abuse, act on VTA GABAergic neurons, ... ...

Abstract	The role of dopaminergic (DA) projections from the ventral tegmental area (VTA) in appetitive and rewarding behavior has been widely studied, but the VTA also has documented DA-independent functions. Several drugs of abuse, act on VTA GABAergic neurons, and most studies have focused on local inhibitory connections. Relatively little is known about VTA GABA projection neurons and their connections to brain sites outside the VTA. This study employed viral-vector-mediated cell-type-specific anterograde tracing, classical retrograde tracing, and immunohistochemistry to characterize VTA GABA efferents throughout the brain. We found that VTA GABA neurons project widely to forebrain and brainstem targets, including the ventral pallidum, lateral and magnocellular preoptic nuclei, lateral hypothalamus, and lateral habenula. Minor projections also go to central amygdala, mediodorsal thalamus, dorsal raphe, and deep mesencephalic nuclei, and sparse projections go to prefrontal cortical regions and to nucleus accumbens shell and core. These projections differ from the major VTA DA target regions. Retrograde tracing studies confirmed results from the anterograde experiments and differences in projections from VTA subnuclei. Retrogradely labeled GABA neurons were not numerous, and most non-tyrosine hydroxylase/retrogradely labeled cells lacked GABAergic markers. Many non-TH/retrogradely labeled cells projecting to several areas expressed VGluT2. VTA GABA and glutamate neurons project throughout the brain, most prominently to regions with reciprocal connections to the VTA. These data indicate that VTA GABA and glutamate neurons may have more DA-independent functions than previously recognized.
MeSH term(s)	Animals ; Cell Count ; Choline O-Acetyltransferase/metabolism ; Dependovirus/physiology ; Efferent Pathways/physiology ; GABAergic Neurons/physiology ; Glutamate Decarboxylase ; Glutamates/metabolism ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Stilbamidines/metabolism ; Substance P/metabolism ; Tyrosine 3-Monooxygenase/metabolism ; Ventral Tegmental Area/cytology ; Vesicular Glutamate Transport Protein 2 ; Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
Chemical Substances	2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt ; Glutamates ; Luminescent Proteins ; Slc17a6 protein, mouse ; Stilbamidines ; Vesicular Glutamate Transport Protein 2 ; Vesicular Inhibitory Amino Acid Transport Proteins ; Viaat protein, mouse ; Substance P (33507-63-0) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2) ; Choline O-Acetyltransferase (EC 2.3.1.6) ; Glutamate Decarboxylase (EC 4.1.1.15) ; glutamate decarboxylase 1 (EC 4.1.1.15) ; glutamate decarboxylase 2 (EC 4.1.1.15)
Language	English
Publishing date	2014-04-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.23603
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Ub I Zs.66: Show issues

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Article ; Online: Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell.

Sharf, Ruth / Sarhan, Maysa / Dileone, Ralph J

Biological psychiatry

2008 Volume 64, Issue 3, Page(s) 175–183

Abstract: Background: The lateral hypothalamic neuropeptide orexin (or hypocretin) is implicated in drug addiction. Although a role for orexin has been shown in reward and dependence, the molecular and neural mechanisms are unclear. We investigated the mechanism ... ...

Abstract	Background: The lateral hypothalamic neuropeptide orexin (or hypocretin) is implicated in drug addiction. Although a role for orexin has been shown in reward and dependence, the molecular and neural mechanisms are unclear. We investigated the mechanism and neuroanatomic basis of orexin's role in morphine withdrawal. Methods: C57BL/6J mice received chronic morphine followed by naloxone (0 or 1 mg/kg, subcutaneous) to precipitate withdrawal. Before naloxone, mice received SB-334867 (0 or 20 mg/kg, intraperitoneal), an orexin 1 receptor (Ox1r) antagonist. Using immunohistochemistry, c-Fos, a marker of cell activation, was quantified in the nucleus accumbens (Acb), lateral hypothalamus (LH), ventral tegmental area (VTA), and locus coeruleus (LC). Retrograde tracing with fluorogold (FG) was performed to determine whether orexin neurons project directly to the Acb. Results: SB-334867 before naloxone significantly attenuated withdrawal symptoms. Withdrawal was accompanied by an increase in c-Fos expression in the Acb shell (AcbSh), which was reduced by SB-334867 but had no effect on the VTA or the LC. Morphine withdrawal increased c-Fos expression in the dorsomedial (DMH) and perifornical (PFA) regions but not in the lateral region of the LH (LLH). Orexin neurons do not appear to form direct connections with Acb neurons. Conclusions: Altogether, these data demonstrate that orexin, acting via Ox1r, is critical for the expression of morphine withdrawal. AcbSh activation during withdrawal is dependent on Ox1r function and is likely mediated by indirect action of LH orexin neurons.
MeSH term(s)	Analysis of Variance ; Animals ; Benzoxazoles/pharmacology ; Intracellular Signaling Peptides and Proteins/metabolism ; Locus Coeruleus/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Morphine/administration & dosage ; Naloxone/therapeutic use ; Naphthyridines ; Narcotic Antagonists/therapeutic use ; Narcotics/administration & dosage ; Neuropeptides/metabolism ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Orexins ; Proto-Oncogene Proteins c-fos/metabolism ; Stilbamidines/metabolism ; Substance Withdrawal Syndrome/drug therapy ; Substance Withdrawal Syndrome/metabolism ; Substance Withdrawal Syndrome/pathology ; Urea/analogs & derivatives ; Urea/pharmacology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/metabolism
Chemical Substances	1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea ; 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt ; Benzoxazoles ; Intracellular Signaling Peptides and Proteins ; Naphthyridines ; Narcotic Antagonists ; Narcotics ; Neuropeptides ; Orexins ; Proto-Oncogene Proteins c-fos ; Stilbamidines ; Naloxone (36B82AMQ7N) ; Morphine (76I7G6D29C) ; Urea (8W8T17847W)
Language	English
Publishing date	2008-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2008.03.006
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Zs.A 720: Show issues

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Article ; Online: Increased serum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: a prospective study.

D'Sa, Carrol / Fox, Helen C / Hong, Adam K / Dileone, Ralph J / Sinha, Rajita

Biological psychiatry

2011 Volume 70, Issue 8, Page(s) 706–711

Abstract: Background: Cocaine dependence is associated with high relapse rates, but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central brain-derived neurotrophic factor (BDNF) in ...

Abstract	Background: Cocaine dependence is associated with high relapse rates, but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central brain-derived neurotrophic factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and whether it is predictive of subsequent relapse risk. Methods: Serum samples were collected across three consecutive mornings from 35 treatment-engaged, 3-week-abstinent cocaine-dependent inpatients (17 males/18 females) and 34 demographically matched hospitalized healthy control participants (17 males/17 females). Cocaine-dependent individuals were prospectively followed on days 14, 30, and 90 posttreatment discharge to assess cocaine relapse outcomes. Time to cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine use (quantity) were the main outcome measures. Results: High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared with healthy control participants (p < .001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: 1.09, p < .05), greater number of days (p < .05), and higher total amounts of cocaine used (p = .05). Conclusions: High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence.
MeSH term(s)	Adult ; Biomarkers/blood ; Brain-Derived Neurotrophic Factor/blood ; Case-Control Studies ; Cocaine-Related Disorders/blood ; Female ; Humans ; Male ; Prospective Studies ; Recurrence ; Time Factors
Chemical Substances	Biomarkers ; Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2011-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2011.05.013
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Zs.A 720: Show issues

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Article ; Online: Anxiolytic function of the orexin 2/hypocretin A receptor in the basolateral amygdala.

Arendt, David H / Hassell, James / Li, Hao / Achua, Justin K / Guarnieri, Douglas J / Dileone, Ralph J / Ronan, Patrick J / Summers, Cliff H

Psychoneuroendocrinology

2013 Volume 40, Page(s) 17–26

Abstract: The orexin/hypocretin system interacts with many of the same circuitries contributing to stress-associated disorders like depression and anxiety. These include potentially reciprocal connections with corticotropin releasing factor (CRF) neurons which ... ...

Abstract	The orexin/hypocretin system interacts with many of the same circuitries contributing to stress-associated disorders like depression and anxiety. These include potentially reciprocal connections with corticotropin releasing factor (CRF) neurons which drive the hypothalamic-pituitary-adrenal (HPA) endocrine response in addition to having an anxiogenic effect in the central amygdala (CeA). Antagonism of the orexin type 1 receptor (Orx1) in the hypothalamus has also been shown to block panic attacks. However, few studies have investigated the effect of orexinergic signaling in the basolateral amygdala (BLA) which is responsible for contextual fear, and modulates the activity of the CeA. To this end, we chronically stressed c57bl/6 mice with social defeat and examined the gene expression of the orexin receptors in the BLA. We found that the transcripts for the Orx1 and Orx2 receptors diverged in the BLA with Orx1 increasing and Orx2 decreasing in animals that were susceptible to the chronic defeat. These changes were not seen in the prelimbic cortex (PrL) which sends efferents to the BLA. We then tried to recapitulate these expression patterns in the BLA using short hairpin interfering sequences delivered by adeno-associated viruses to knock down the orexin receptors. While the Orx1 knockdown did reduce locomotor activity, it did not decrease depressive or anxious behaviors. Knocking down the Orx2 receptors in the BLA increased anxious behavior as measured by reduced social preference and reduced time spent in the center of an open field. Due to the divergent expression patterns of the two receptors in response to chronic stress, orexinergic activity in the BLA may be responsible for bidirectional modulation of anxious behavior. Furthermore, these data raise the possibility that an Orx2 agonist may serve as an effective means to treat anxiety disorders.
MeSH term(s)	Amygdala/drug effects ; Amygdala/metabolism ; Animals ; Animals, Genetically Modified ; Anti-Anxiety Agents/metabolism ; Anxiety/genetics ; Anxiety/metabolism ; Behavior, Animal/drug effects ; Dominance-Subordination ; Fear/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Orexin Receptor Antagonists ; Orexin Receptors/genetics ; Orexin Receptors/metabolism ; RNA, Small Interfering/pharmacology ; Resilience, Psychological/drug effects
Chemical Substances	Anti-Anxiety Agents ; Cd200r1 protein, mouse ; Hcrtr1 protein, mouse ; Orexin Receptor Antagonists ; Orexin Receptors ; RNA, Small Interfering
Language	English
Publishing date	2013-10-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2013.10.010
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Zs.A 1235: Show issues

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Article ; Online: The orbitofrontal cortex regulates outcome-based decision-making via the lateral striatum.

Gourley, Shannon L / Olevska, Anastasia / Zimmermann, Kelsey S / Ressler, Kerry J / Dileone, Ralph J / Taylor, Jane R

The European journal of neuroscience

2013 Volume 38, Issue 3, Page(s) 2382–2388

Abstract: The orbitofrontal cortex (oPFC) sends substantial projections to the ventrolateral striatum and aspects of the nucleus accumbens that are, functionally, poorly understood. This is despite probable cortico-striatal involvement in multiple diseases such as ...

Abstract	The orbitofrontal cortex (oPFC) sends substantial projections to the ventrolateral striatum and aspects of the nucleus accumbens that are, functionally, poorly understood. This is despite probable cortico-striatal involvement in multiple diseases such as addiction and obsessive-compulsive disorder. Here we surgically disconnected the oPFC from the ventrolateral striatum using unilateral asymmetric lesions in mice and classified instrumental decision-making strategies. Mice with symmetric lesions that spared one oPFC-striatal network served as controls. As a complementary approach, we selectively knocked down Brain-derived neurotrophic factor (Bdnf) bilaterally in the oPFC and ascertained behavioral and neurobiological consequences within the downstream striatum. oPFC-striatal disconnection and oPFC Bdnf knockdown blocked sensitivity to outcome-predictive relationships in both food-reinforced and cocaine-associated settings. Bdnf knockdown simultaneously regulated striatal BDNF expression, and striatal c-Fos predicted sensitivity to action-outcome associative contingencies. Previous evidence strongly implicates the dorsolateral striatum in stimulus-response habit formation. Our findings thus provide novel evidence for functional compartmentalisation within the lateral striatum, with the dorsal compartment subserving classical stimulus-response habit systems and a ventral compartment coordinating outcome-based decision-making via oPFC interactions. This compartmentalisation may apply to both 'natural', as in the case of food-reinforced behavior, and 'pathological', as in the case of cocaine-seeking, contexts.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Conditioning, Operant/physiology ; Corpus Striatum/physiology ; Decision Making/physiology ; Frontal Lobe/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neural Pathways/physiology
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2013-05-08
Publishing country	France
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.12239
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Article ; Online: Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.

D'Agostino, Giuseppe / Lyons, David J / Cristiano, Claudia / Burke, Luke K / Madara, Joseph C / Campbell, John N / Garcia, Ana Paula / Land, Benjamin B / Lowell, Bradford B / Dileone, Ralph J / Heisler, Lora K

eLife

2016 Volume 5

Abstract: The nucleus of the solitary tract (NTS) is a key gateway for meal-related signals entering the brain from the periphery. However, the chemical mediators crucial to this process have not been fully elucidated. We reveal that a subset of NTS neurons ... ...

Abstract	The nucleus of the solitary tract (NTS) is a key gateway for meal-related signals entering the brain from the periphery. However, the chemical mediators crucial to this process have not been fully elucidated. We reveal that a subset of NTS neurons containing cholecystokinin (CCK(NTS)) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCK(NTS) neurons provide a distinctive innervation of the paraventricular nucleus of the hypothalamus (PVH), with fibers and varicosities in close apposition to a subset of melanocortin-4 receptor (MC4R(PVH)) cells, which are also responsive to CCK. Optogenetic activation of CCK(NTS) axon terminals within the PVH reveal the satiating function of CCK(NTS) neurons to be mediated by a CCK(NTS)→PVH pathway that also encodes positive valence. These data identify the functional significance of CCK(NTS) neurons and reveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.
MeSH term(s)	Animals ; Appetite ; Brain Mapping ; Cholecystokinin/metabolism ; Mice ; Neural Pathways/anatomy & histology ; Optogenetics ; Paraventricular Hypothalamic Nucleus/physiology ; Solitary Nucleus/physiology
Chemical Substances	Cholecystokinin (9011-97-6)
Language	English
Publishing date	2016-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.12225
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In stock of ZB MED Cologne/Königswinter

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Kategorien

In stock of ZB MED Cologne/Königswinter

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Full text online

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Kategorien

In stock of ZB MED Cologne/Königswinter

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Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito