Trends in Endocrinology & Metabolism
ReviewNeural Circuit Mechanisms Underlying Emotional Regulation of Homeostatic Feeding
Section snippets
Behavioral Interactions between Feeding and Emotion
Since feeding is essential for survival, the brain has evolved multiple overlapping mechanisms to assure adequate levels of food intake during changing energy demands 1, 2, 3, 4. Ultimately, the decision to eat is controlled by neuronal activity in distributed feeding centers that primarily reside in the hypothalamus, hindbrain, and limbic brain regions 1, 2, 3, 4. These feeding centers are anatomically connected with broadly distributed brain regions that convey emotional information.
Regulation of Diverse Emotional Behaviors by Arcuate Feeding Neurons
It is well recognized that the arcuate nucleus of the hypothalamus (ARC) has a primary role in feeding 1, 2, 3, 4. For example, chemogenetic (see Glossary) and optogenetic activation of agouti-related protein-expressing ARC (ARCAGRP) neurons increases feeding in sated mice 9, 10. Selective activation of ARCAGRP neuronal projections to the paraventricular hypothalamus (PVH), the LH, or the anterior bed nucleus of the stria terminalis (aBNST) was sufficient to rapidly increase food intake in
LH Modulates the Mesolimbic Reward Circuitry
Along with the ARC, the LH is well recognized as a ‘feeding center’ in the brain. Much of the LH’s effect on feeding has been attributed to the close association between the LH and the ventral tegmental area (VTA) of the mesolimbic reward system [22]. Of particular importance to emotion and feeding, disruption in the mesolimbic dopamine system comprising the nucleus accumbens (NAc) and the VTA is linked to changes in mood and emotions 23, 24, 25. However, the functional interactions between
LH GABAergic Neurons Receive Inputs from Emotional Circuitry
Given that LH GABAergic neurons potently regulate feeding and emotional processes, synaptic inputs to these neurons are also likely to regulate feeding and emotional behavior since integrated synaptic strength controls neural activity. LH GABAergic neurons receive synaptic inputs from brain regions classically involved in emotion-related behaviors including the lateral septum (LS) [31] and NAc [23] and manipulation of these inputs to the LH regulates feeding. For example, a recent study
LH Glutamatergic Neurons Reduce Feeding via Connections with Emotional Circuitry
In contrast to the orexigenic role of LH GABAergic neurons, glutamatergic neurons in the LH exert negative effects on feeding 42, 43. For instance, optogenetic stimulation of LH glutamatergic neurons reduced feeding and was aversive while selective ablation of LH glutamatergic neurons increased food intake 42, 43. The acute appetite-reducing effect of LH glutamatergic neurons appears to be independent of projections to the VTA as selective optogenetic stimulation or inhibition of LH
Newly Identified Hippocampal and Amygdalar Feeding Circuits
As discussed above, primary feeding centers localized in the ARC and LH, in addition to regulating feeding, also modulate emotional processes. However, emotion-related brain regions including the hippocampus and amygdala modulate feeding behavior [5]. For instance, the hippocampal formation (HPC) has been classically implicated in emotional behaviors including anxiety and depressive behavior 52, 53, 54, 55. In addition to the hippocampus’ role in emotion, numerous lines of evidence support a
Concluding Remarks and Future Perspectives
It has been proposed that emotions evolved to reinforce behaviors that promote survival [82]. Since feeding is essential for survival, neural circuit overlap between brain regions controlling feeding and emotions is hardly surprising. At the neural circuit level, key hypothalamic feeding centers (such as the ARC and LH) are bidirectionally connected to brain regions that convey emotional information, including the vHPC, amygdala, VTA, NAc, LS, and BNST (Table 1). These bidirectional connections
Acknowledgments
The authors apologize to all colleagues whose studies were not discussed or cited in this review because of space limitations. Y.Y. is funded by the State University of New York and National Institute of Mental Health (R01MH10944A).
Glossary
- Chemogenetics
- a behavioral neuroscience approach utilizing designer receptors exclusively activated by designer drugs (DREADDs) that couple to intracellular signaling pathways to selectively activate or inhibit defined neuronal cell types. Targeted neurons are activated or inhibited via injection of a blood–brain barrier-permeable ligand that selectively binds to these receptors to activate intracellular signaling pathways.
- Chronic restraint stress
- animal model of stress-induced behavior
References (97)
Neural circuits and motivational processes for hunger
Curr. Opin. Neurobiol.
(2013)Circuits controlling energy balance and mood: inherently intertwined or just complicated intersections?
Cell Metab.
(2014)Depression and obesity
Biol. Psychiatry
(2003)Parallel, redundant circuit organization for homeostatic control of feeding behavior
Cell
(2013)Hunger-driven motivational state competition
Neuron
(2016)Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding
Cell
(2015)Preemptive stimulation of AgRP neurons in fed mice enables conditioned food seeking under threat
Curr. Biol.
(2016)Decoding neural circuits that control compulsive sucrose seeking
Cell
(2015)Inhibitory input from the lateral hypothalamus to the ventral tegmental area disinhibits dopamine neurons and promotes behavioral activation
Neuron
(2016)Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors
Cell
(2015)
Regulation of affect by the lateral septum: implications for neuropsychiatry
Brain Res. Brain Rev.
Accumbal D1R neurons projecting to lateral hypothalamus authorize feeding
Neuron
Activation of GABAA and GABAB receptors in the lateral septum increases sucrose intake by differential stimulation of sucrose licking activity
Behav. Brain Res.
Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance
Cell Metab.
Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons
Neuropharmacology
Are the dorsal and ventral hippocampus functionally distinct structures?
Neuron
Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus
Neuron
Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K–Akt signaling
Biol. Psychiatry
The anterior medial temporal lobes: their role in food intake and body weight regulation
Physiol. Behav.
BLA to vHPC inputs modulate anxiety-related behaviors
Neuron
Gating of fear in prelimbic cortex by hippocampal and amygdala inputs
Neuron
Forebrain networks and the control of feeding by environmental learned cues
Physiol. Behav.
Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance
Cell Metab.
Parabrachial CGRP neurons control meal termination
Cell Metab.
Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors
Brain Res.
Anorexia nervosa: aetiology, assessment, and treatment
Lancet Psychiatry
Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus→ midbrain pathway for feeding behavior
Neuron
Neurobiology of food intake in health and disease
Nat. Rev. Neurosci.
Functional organization of neuronal and humoral signals regulating feeding behavior
Annu. Rev. Nutr.
From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior
Nat. Neurosci.
Association between obesity and psychiatric disorders in the US adult population
Arch. Gen. Psychiatry
The relation of body mass index to depressive symptoms
Can. J. Public Health
AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training
Nat. Neurosci.
Rapid reversible activaiton of Agrp neurons drives feeding behavior in mice
J. Clin. Invest.
Deconstruction of a neural circuit for hunger
Nature
A neural basis for melanocortin-4 receptor-regulated appetite
Nat. Neurosci.
Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state
Nat. Neurosci.
Neurons for hunger and thirst transmit a negative-valence teaching signal
Nature
Hunger neurons drive feeding through a sustained, positive reinforcement signal
Elife
Agouti-related protein neuron circuits that regulate appetite
Neuroendocrinology
Neuronal circuits for fear and anxiety
Nat. Rev. Neurosci.
Lateral hypothalamic circuits for feeding and reward
Nat. Neurosci.
The brain reward circuitry in mood disorders
Nat. Rev. Neurosci
Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons
Nature
Neuronal correlates of depression
Cell. Mol. Life Sci.
Lateral hypothalamus GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli
Neuropsychopharmacology
Dopamine neurons modulate neural encoding and expression of depression-related behavior
Nature
Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens
Nature
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