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The role of the lateral hypothalamus and orexin in ingestive behavior: a model for the translation of past experience and sensed deficits into motivated behaviors.

Hurley SW, Johnson AK - Front Syst Neurosci (2014)

Bottom Line: The LHA also receives inputs from brain areas involved in reward-related learning and orexin neuron activation can become conditioned to environmental stimuli that are associated with rewards.In turn, this information is "fed into" mesolimbic circuitry to influence the performance of motivated behaviors.This hypothesis may foster experiments that will result in an improved understanding of LHA function.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Iowa Iowa City, IA, USA.

ABSTRACT
The hypothalamus has been recognized for its involvement in both maintaining homeostasis and mediating motivated behaviors. The present article discusses a region of the hypothalamus known as the lateral hypothalamic area (LHA). It is proposed that brain nuclei within the LHA including the dorsal region of the lateral hypothalamus (LHAd) and perifornical area (PeF) provide a link between neural systems that regulate homeostasis and those that mediate appetitive motivated behaviors. Functional and immunohistochemical data indicate that the LHA promotes many motivated behaviors including food intake, water intake, salt intake, and sexual behavior. Anatomical tracing experiments demonstrate that the LHA is positioned to receive inputs from brain areas involved in regulating body fluid and energy homeostasis. Regions within the LHA send dense projections to the ventral tegmental area (VTA), providing a pathway for the LHA to influence dopaminergic systems generally recognized to be involved in motivated behaviors and their reinforcement. Furthermore, the LHA contains neurons that synthesize orexin/hypocretin, a neuropeptide that promotes many appetitive motivated behaviors. The LHA also receives inputs from brain areas involved in reward-related learning and orexin neuron activation can become conditioned to environmental stimuli that are associated with rewards. Therefore, it is hypothesized that the LHA integrates signaling from areas that regulate body fluid and energy balance and reward-related learning. In turn, this information is "fed into" mesolimbic circuitry to influence the performance of motivated behaviors. This hypothesis may foster experiments that will result in an improved understanding of LHA function. An improved understanding of LHA function may aid in treating disorders that are associated with an excess or impairment in the expression of ingestive behavior including obesity, anorexia, impairments in thirst, salt gluttony, and salt deficiency.

No MeSH data available.


Related in: MedlinePlus

Unpublished data from authors. Co-labeling between orexin and VTA projection neurons in the hypothalamus. The retrograde tracer Fluoro-Gold (Fluorochrome, Denver CO) was microinjected (2% in 250 nl) into the VTA, brains were collected and sliced at 40µm, and then tissue was stained for orexin A immunoreactivity via overnight incubation with an anti-orexin A antibody (1:8000, Phoenix Pharmaceuticals, Burlingame CA) and visualized through incubation with Alexa Fluor 647 (1:200, Jackson ImmunoResearch, West Grove PA) for 1 h. Images (A–I) were taken at 10x magnification and images (J–L) were taken at 40x. In the DMH (A–C), significant orexin neuron labeling was observed (A) in addition to retrogradely labeled neurons from the VTA (B), and some orexin neurons projected to the VTA (C, yellow labeling). In the PeF (D–F) a subset of orexin neurons (D) and retrogradely labeled neurons from the VTA (E) co-localized (F). In the LHAd (G–I) a subset of orexin neurons (G) and retrogradely neurons from the VTA (H) colocalized (I). A 40x magnification of labeling observed in the DMH is presented in panels (J–L). Double-labeled neurons are indicated by white arrows. v = ventricle, f = fornix.
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Figure 1: Unpublished data from authors. Co-labeling between orexin and VTA projection neurons in the hypothalamus. The retrograde tracer Fluoro-Gold (Fluorochrome, Denver CO) was microinjected (2% in 250 nl) into the VTA, brains were collected and sliced at 40µm, and then tissue was stained for orexin A immunoreactivity via overnight incubation with an anti-orexin A antibody (1:8000, Phoenix Pharmaceuticals, Burlingame CA) and visualized through incubation with Alexa Fluor 647 (1:200, Jackson ImmunoResearch, West Grove PA) for 1 h. Images (A–I) were taken at 10x magnification and images (J–L) were taken at 40x. In the DMH (A–C), significant orexin neuron labeling was observed (A) in addition to retrogradely labeled neurons from the VTA (B), and some orexin neurons projected to the VTA (C, yellow labeling). In the PeF (D–F) a subset of orexin neurons (D) and retrogradely labeled neurons from the VTA (E) co-localized (F). In the LHAd (G–I) a subset of orexin neurons (G) and retrogradely neurons from the VTA (H) colocalized (I). A 40x magnification of labeling observed in the DMH is presented in panels (J–L). Double-labeled neurons are indicated by white arrows. v = ventricle, f = fornix.

Mentions: Some of the strongest evidence supporting a role for the hypothalamus in promoting motivated behavior comes from studies examining orexin (AKA hypocretin). Orexin is a neuropeptide that is expressed primarily in the caudal half of the hypothalamus where it is distributed in an arc that extends from the DMH to the LHAd (Figure 1). Orexin appears to be the only known centralized peptide neurotransmitter system as orexin neurons from a relatively circumscribed area send distal projections to diverse brain areas (Peyron et al., 1998). Functionally, orexin neurons have been heavily implicated in a variety of motivated behaviors (Harris et al., 2005; Borgland et al., 2009). Orexin has received significant attention for its capacity to elicit robust food intake (hence the name orexin; Sakurai et al., 1998; Choi et al., 2010) but it is also involved in promoting thirst, salt appetite (Kunii et al., 1999; Hurley et al., 2013a), and reproductive behavior (Muschamp et al., 2007; Di Sebastiano et al., 2010). Orexin neurons can be putatively organized into three cell-clusters in the hypothalamus: a cluster in the DMH, perifornical area (PeF), and the LHAd (Figure 1). Both the PeF and LHAd are regions located in the LHA while the DMH lies medially where it abuts the third ventricle. Each orexin cell-cluster contains a subset of orexin neurons that project to the VTA (Figure 1; Fadel and Deutch, 2002), and orexin is capable of depolarizing neurons in the VTA (Korotkova et al., 2003). Therefore, orexin neurons provide a mechanism for areas within the LHA to tap into systems traditionally conceived of as being involved in motivation and reward. Evidence also indicates that orexin neurons have direct projections to the nucleus accumbens shell (Peyron et al., 1998; Kampe et al., 2009) where they may act to promote motivated behaviors (Thorpe and Kotz, 2005).


The role of the lateral hypothalamus and orexin in ingestive behavior: a model for the translation of past experience and sensed deficits into motivated behaviors.

Hurley SW, Johnson AK - Front Syst Neurosci (2014)

Unpublished data from authors. Co-labeling between orexin and VTA projection neurons in the hypothalamus. The retrograde tracer Fluoro-Gold (Fluorochrome, Denver CO) was microinjected (2% in 250 nl) into the VTA, brains were collected and sliced at 40µm, and then tissue was stained for orexin A immunoreactivity via overnight incubation with an anti-orexin A antibody (1:8000, Phoenix Pharmaceuticals, Burlingame CA) and visualized through incubation with Alexa Fluor 647 (1:200, Jackson ImmunoResearch, West Grove PA) for 1 h. Images (A–I) were taken at 10x magnification and images (J–L) were taken at 40x. In the DMH (A–C), significant orexin neuron labeling was observed (A) in addition to retrogradely labeled neurons from the VTA (B), and some orexin neurons projected to the VTA (C, yellow labeling). In the PeF (D–F) a subset of orexin neurons (D) and retrogradely labeled neurons from the VTA (E) co-localized (F). In the LHAd (G–I) a subset of orexin neurons (G) and retrogradely neurons from the VTA (H) colocalized (I). A 40x magnification of labeling observed in the DMH is presented in panels (J–L). Double-labeled neurons are indicated by white arrows. v = ventricle, f = fornix.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230038&req=5

Figure 1: Unpublished data from authors. Co-labeling between orexin and VTA projection neurons in the hypothalamus. The retrograde tracer Fluoro-Gold (Fluorochrome, Denver CO) was microinjected (2% in 250 nl) into the VTA, brains were collected and sliced at 40µm, and then tissue was stained for orexin A immunoreactivity via overnight incubation with an anti-orexin A antibody (1:8000, Phoenix Pharmaceuticals, Burlingame CA) and visualized through incubation with Alexa Fluor 647 (1:200, Jackson ImmunoResearch, West Grove PA) for 1 h. Images (A–I) were taken at 10x magnification and images (J–L) were taken at 40x. In the DMH (A–C), significant orexin neuron labeling was observed (A) in addition to retrogradely labeled neurons from the VTA (B), and some orexin neurons projected to the VTA (C, yellow labeling). In the PeF (D–F) a subset of orexin neurons (D) and retrogradely labeled neurons from the VTA (E) co-localized (F). In the LHAd (G–I) a subset of orexin neurons (G) and retrogradely neurons from the VTA (H) colocalized (I). A 40x magnification of labeling observed in the DMH is presented in panels (J–L). Double-labeled neurons are indicated by white arrows. v = ventricle, f = fornix.
Mentions: Some of the strongest evidence supporting a role for the hypothalamus in promoting motivated behavior comes from studies examining orexin (AKA hypocretin). Orexin is a neuropeptide that is expressed primarily in the caudal half of the hypothalamus where it is distributed in an arc that extends from the DMH to the LHAd (Figure 1). Orexin appears to be the only known centralized peptide neurotransmitter system as orexin neurons from a relatively circumscribed area send distal projections to diverse brain areas (Peyron et al., 1998). Functionally, orexin neurons have been heavily implicated in a variety of motivated behaviors (Harris et al., 2005; Borgland et al., 2009). Orexin has received significant attention for its capacity to elicit robust food intake (hence the name orexin; Sakurai et al., 1998; Choi et al., 2010) but it is also involved in promoting thirst, salt appetite (Kunii et al., 1999; Hurley et al., 2013a), and reproductive behavior (Muschamp et al., 2007; Di Sebastiano et al., 2010). Orexin neurons can be putatively organized into three cell-clusters in the hypothalamus: a cluster in the DMH, perifornical area (PeF), and the LHAd (Figure 1). Both the PeF and LHAd are regions located in the LHA while the DMH lies medially where it abuts the third ventricle. Each orexin cell-cluster contains a subset of orexin neurons that project to the VTA (Figure 1; Fadel and Deutch, 2002), and orexin is capable of depolarizing neurons in the VTA (Korotkova et al., 2003). Therefore, orexin neurons provide a mechanism for areas within the LHA to tap into systems traditionally conceived of as being involved in motivation and reward. Evidence also indicates that orexin neurons have direct projections to the nucleus accumbens shell (Peyron et al., 1998; Kampe et al., 2009) where they may act to promote motivated behaviors (Thorpe and Kotz, 2005).

Bottom Line: The LHA also receives inputs from brain areas involved in reward-related learning and orexin neuron activation can become conditioned to environmental stimuli that are associated with rewards.In turn, this information is "fed into" mesolimbic circuitry to influence the performance of motivated behaviors.This hypothesis may foster experiments that will result in an improved understanding of LHA function.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Iowa Iowa City, IA, USA.

ABSTRACT
The hypothalamus has been recognized for its involvement in both maintaining homeostasis and mediating motivated behaviors. The present article discusses a region of the hypothalamus known as the lateral hypothalamic area (LHA). It is proposed that brain nuclei within the LHA including the dorsal region of the lateral hypothalamus (LHAd) and perifornical area (PeF) provide a link between neural systems that regulate homeostasis and those that mediate appetitive motivated behaviors. Functional and immunohistochemical data indicate that the LHA promotes many motivated behaviors including food intake, water intake, salt intake, and sexual behavior. Anatomical tracing experiments demonstrate that the LHA is positioned to receive inputs from brain areas involved in regulating body fluid and energy homeostasis. Regions within the LHA send dense projections to the ventral tegmental area (VTA), providing a pathway for the LHA to influence dopaminergic systems generally recognized to be involved in motivated behaviors and their reinforcement. Furthermore, the LHA contains neurons that synthesize orexin/hypocretin, a neuropeptide that promotes many appetitive motivated behaviors. The LHA also receives inputs from brain areas involved in reward-related learning and orexin neuron activation can become conditioned to environmental stimuli that are associated with rewards. Therefore, it is hypothesized that the LHA integrates signaling from areas that regulate body fluid and energy balance and reward-related learning. In turn, this information is "fed into" mesolimbic circuitry to influence the performance of motivated behaviors. This hypothesis may foster experiments that will result in an improved understanding of LHA function. An improved understanding of LHA function may aid in treating disorders that are associated with an excess or impairment in the expression of ingestive behavior including obesity, anorexia, impairments in thirst, salt gluttony, and salt deficiency.

No MeSH data available.


Related in: MedlinePlus