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      Sense of Smell as the Central Driver of Pavlovian Appetite Behavior in Mammals

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          Abstract

          The seminal experiments of Ivan Petrovich Pavlov set the stage for an understanding of the physiological concomitants of appetite and feeding behavior. His findings, from careful and creative experimentation, have been uncontested for over a century. One of Pavlov’s most fundamental observations was that activation of salivary, gastric and pancreatic secretions during feeding and sham-feeding, precedes entry of food into the mouth, generating signals to the brain from various sensory pathways. Pavlov referred to this as the “psychic” phase of digestion. However, quite surprisingly, he did not attempt to isolate any single sensory system as the main driver of this phenomenon. Herein we revisit Pavlov’s findings and hypothesize that the evolutionarily-important sense of smell is the pathway most-likely determinant of feeding behavior in mammals. Substantial understandings of olfactory receptors and their neural pathways in the central nervous system have emerged over the past decade. Neurogenic signals, working in concert with hormonal inputs are described, illustrating the ways in which sense of smell determines food-seeking and food-preference. Additionally, we describe how sense of smell affects metabolic pathways relevant to energy metabolism, hunger and satiety as well as a broad range of human behaviors, thereby reinforcing its central biological role in mammals. Intriguing possibilities for future research, based upon this hypothesis, are raised.

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          Most cited references44

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          Sensory detection of food rapidly modulates arcuate feeding circuits.

          Hunger is controlled by specialized neural circuits that translate homeostatic needs into motivated behaviors. These circuits are under chronic control by circulating signals of nutritional state, but their rapid dynamics on the timescale of behavior remain unknown. Here, we report optical recording of the natural activity of two key cell types that control food intake, AgRP and POMC neurons, in awake behaving mice. We find unexpectedly that the sensory detection of food is sufficient to rapidly reverse the activation state of these neurons induced by energy deficit. This rapid regulation is cell-type specific, modulated by food palatability and nutritional state, and occurs before any food is consumed. These data reveal that AgRP and POMC neurons receive real-time information about the availability of food in the external world, suggesting a primary role for these neurons in controlling appetitive behaviors such as foraging that promote the discovery of food.
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            Neurobiology of food intake in health and disease.

            Under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time. However, this homeostatic system can be overridden by the activation of 'emergency response circuits' that mediate feeding responses to emergent or stressful stimuli. Inhibition of these circuits is therefore permissive for normal energy homeostasis to occur, and their chronic activation can cause profound, even life-threatening, changes in body fat mass. This Review highlights how the interplay between homeostatic and emergency feeding circuits influences the biologically defended level of body weight under physiological and pathophysiological conditions.
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              Agouti-related peptide-expressing neurons are mandatory for feeding.

              Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                18 September 2019
                2019
                : 10
                : 1151
                Affiliations
                [1] 1Department of Biomedical Sciences, Cedars-Sinai Medical Center , Los Angeles, CA, United States
                [2] 2Program in the History of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA, United States
                [3] 3Center for Neural Science and Medicine, Cedars-Sinai Medical Center , Los Angeles, CA, United States
                [4] 4Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center , Los Angeles, CA, United States
                Author notes

                Edited by: Stephen O’Keefe, University of Pittsburgh, United States

                Reviewed by: Hélène Volkoff, Memorial University of Newfoundland, Canada; Ivan Manzini, University of Giessen, Germany; Hongxiang Hui, Southern Medical University, China

                *Correspondence: Leon G. Fine, leon.fine@ 123456cshs.org

                This article was submitted to Gastrointestinal Sciences, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2019.01151
                6759725
                31620009
                dce0e5a0-d4ba-4f81-b6f9-be0a1c024388
                Copyright © 2019 Fine and Riera.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 February 2019
                : 26 August 2019
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 62, Pages: 10, Words: 0
                Funding
                Funded by: Esther A. and Joseph Klingenstein Fund 10.13039/100005634
                Funded by: American Diabetes Association 10.13039/100000041
                Categories
                Physiology
                Hypothesis and Theory

                Anatomy & Physiology
                appetite and energy expenditure,food perception,palatability,hypothalamus,ghrelin

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