Neural mechanisms of social homeostasis

In the paper

“even just the perception of isolation (colloquially referred to as loneliness) is associated with poor physical and mental health10,11 and higher mortality rates6,8,12,13.”

What the sources say

• Not checked yetcites [10] Cacioppo JT, Hughes ME, Waite LJ, Hawkley LC & Thisted RA Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses. Psychol. Aging 21, 140– 151 (2006). 16594799 source
• Not checked yetcites [11] Hawkley LC, Masi CM, Berry JD & Cacioppo JT Loneliness is a unique predictor of age-related differences in systolic blood pressure. Psychol. Aging 21, 152– 164 (2006). 16594800 source
• Not checked yetcites [6] Holt-Lunstad J, Smith TB & Layton JB Social Relationships and Mortality Risk: A Meta-analytic Review. PLoS Med 7, e1000316 (2010). PMC2910600 20668659 source
• Not checked yetcites [8] House JS, Landis KR & Umberson D. Social relationships and health. Science 241, 540– 545 (1988). 3399889 source
• Not checked yetcites [12] Holwerda TJ Increased risk of mortality associated with social isolation in older men: only when feeling lonely? Results from the Amsterdam Study of the Elderly (AMSTEL). Psychol. Med. 42, 843– 853 (2012). 21896239 source
• Not checked yetcites [13] Perissinotto CM, Stijacic Cenzer I. & Covinsky KE Loneliness in older persons: a predictor of functional decline and death. Arch. Intern. Med. 172, 1078– 1083 (2012). 22710744 PMC4383762 source

In the paper

“The proportion of the population who live alone has risen3 and an increasing number of people experience loneliness4,5.”

What the sources say

• Not checked yetcites [3] United Nations. United Nations, Department of Economic and Social Affairs, Population Division (2017). Household Size & Composition, 2017 (2017). Available at: https://population.un.org/Household/index.html#/countries. (Accessed: 9th September 2018)
• Not checked yetcites [4] Cacioppo JT & Patrick W. Loneliness: Human Nature and the Need for Social Connection. (W. W. Norton & Company, 2008).
• Not checked yetcites [5] Victor CR & Yang K. The Prevalence of Loneliness Among Adults: A Case Study of the United Kingdom. J. Psychol. 146, 85– 104 (2012). 22303614

In the paper

“The wild species of mice and rats from which laboratory strains were derived are promiscuous and territorial, but show greater social tolerance in high-density living environments and adopt linear dominance hierarchies that promote group stability41.”

What the sources say

• Not checked yetcites [41] Lott DF Intraspecific Variation in the Social Systems of Wild Vertebrates. Behaviour 88, 266– 325 (1984). source

In the paper

“This model proposes that loneliness operates as an aversive signal designed to promote adaptation to the vulnerabilities of being alone and motivate reconnection32.”

What the sources say

• Not checked yetcites [32] Cacioppo JT, Cacioppo S. & Boomsma DI Evolutionary Mechanisms for Loneliness. Cogn. Emot 28, (2014). PMC3855545 24067110 source

In the paper

“A social homeostatic system would be required to (1) monitor social conditions; (2) detect deviation from a homeostatic “set point” in control centers; and (3) activate effector systems to elicit an appropriate response (e.g., strategies to promote social contact).”

In the paper

“We propose that parallel, overlapping circuits mediate the response to social deficit (the output of homeostatic “effector” systems) in an effort to heighten attention to environmental stimuli, motivate social reconnection, and limit emotional distress (Fig. 2).”

In the paper

“Challenges to physiological homeostasis can also elicit motivated behaviors associated with strong negative “drive” states, such as overheating, thirst, and hunger, designed to appropriately adapt/direct behavior19–21.”

What the sources say

• Not checked yetcites [19] Betley JN, Cao ZFH, Ritola KD & Sternson SM Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell 155, 1337– 1350 (2013). 24315102 PMC3970718
• Not checked yetcites [20] Oka Y, Ye M. & Zuker CS Thirst Driving and Suppressing Signals Encoded by Distinct Neural Populations in the Brain. Nature 520, 349– 352 (2015). 25624099 PMC4401619
• Not checked yetcites [21] Zimmerman CA Thirst neurons anticipate the homeostatic consequences of eating and drinking. Nature 537, 680– 684 (2016). 27487211 PMC5161740 source

In the paper

“A deficit in social connections (whether perceived or actual) would be predicted to engage this system.”

In the paper

“They show biparental care towards offspring, tend to live in extended families48,49, and are well-utilized in the study of social bonding and isolation.”

What the sources say

• Not checked yetcites [48] Carter CS, DeVries AC & Getz LL Physiological substrates of mammalian monogamy: the prairie vole model. Neurosci. Biobehav. Rev. 19, 303– 314 (1995). 7630584
• Not checked yetcites [49] Getz LL & Hofmann JE Social organization in free-living prairie voles, Microtus ochrogaster. Behav. Ecol. Sociobiol. 18, 275– 282 (1986).

In the paper

“Here, we evaluate social isolation–induced adaptations in these rodents, in light of the phenotype of human loneliness, which may also represent a state of activation of “social homeostatic systems.””

In the paper

“This “supraorganismal” structure requires tight regulation to maintain stable hierarchical social organization when met with changes in the environment or internal composition16,17.”

What the sources say

• Not checked yetcites [16] Emerson AE Regenerate Behavior and Social Homeostasis of Termites. Ecology 37, 248– 258 (1956).
• Not checked yetcites [17] Wheeler WM The ant-colony as an organism. J. Morphol. 22, 307– 325 (1911).

In the paper

“loneliness is theorized to represent an “adaptive predisposition” providing the motivational drive to maintain social contact and prevent the aversive consequences of isolation14,15.”

What the sources say

• Not checked yetcites [14] Cacioppo JT Loneliness Across Phylogeny and a Call for Comparative Studies and Animal Models. Perspect. Psychol. Sci. J. Assoc. Psychol. Sci. 10, 202– 212 (2015). PMC5090712 25910390
• Not checked yetcites [15] Eisenberger NI & Cole SW Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nat. Neurosci. 15, 669– 674 (2012). 22504347 source

In the paper

“This discrepancy may reflect the shorter duration of isolation or the different species under study.”

In the paper

“high self-reported loneliness in humans has been associated with elevated daily cortisol output62–66 and a flattening of diurnal cortisol rhythm65, suggesting poor regulation of the HPA axis67.”

What the sources say

• Not checked yetcites [62] Adam EK, Hawkley LC, Kudielka BM & Cacioppo JT Day-to-day dynamics of experience--cortisol associations in a population-based sample of older adults. Proc. Natl. Acad. Sci. U. S. A. 103, 17058– 17063 (2006). 17075058 PMC1636578 source
• Not checked yetcites [63] Cacioppo JT Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies. Int. J. Psychophysiol. Off. J. Int. Organ. Psychophysiol. 35, 143– 154 (2000). 10677643
• Not checked yetcites [64] Cole SW Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Proc. Natl. Acad. Sci. 112, 15142– 15147 (2015). 26598672 PMC4679065 source
• Not checked yetcites [65] Doane LD & Adam EK Loneliness and Cortisol: Momentary, Day-to-day, and Trait Associations. Psychoneuroendocrinology 35, 430– 441 (2010). 19744794 PMC2841363 source
• Not checked yetcites [66] Pressman SD Loneliness, social network size, and immune response to influenza vaccination in college freshmen. Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc. 24, 297– 306 (2005). 15898866 source
• Not checked yetcites [67] Cacioppo JT, Hawkley LC, Norman GJ & Berntson GG Social isolation. Ann. N. Y. Acad. Sci. 1231, 17– 22 (2011). 21651565 PMC3166409 source

In the paper

“Lonely individuals often show high levels of anxiety51,52, and hypervigilant responses to negative social stimuli, suggestive of heightened recruitment of attentional and self-preservation mechanisms53.”

What the sources say

• Not checked yetcites [51] Ginter EJ, Glauser A. & Richmond BO Loneliness, Social Support, and Anxiety among Two South Pacific Cultures. Psychol. Rep. 74, 875– 879 (1994). 8058870
• Not checked yetcites [52] Stednitz JN & Epkins CC Girls’ and mothers’ social anxiety, social skills, and loneliness: associations after accounting for depressive symptoms. J. Clin. Child Adolesc. Psychol. Off. J. Soc. Clin. Child Adolesc. Psychol. Am. Psychol. Assoc. Div. 53 35, 148– 154 (2006). 16390310 source
• Not checked yetcites [53] Cacioppo S. Loneliness and implicit attention to social threat: A high-performance electrical neuroimaging study. Cogn. Neurosci. 7, 138– 159 (2016). 26274315

In the paper

“In adult rats, a 24-hour isolation increased tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine synthesis) mRNA in the LC, an effect which could be blocked by an AT1 receptor antagonist81.”

What the sources say

• Not checked yetcites [81] Saavedra JM A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding. Neuropsychopharmacology 31, 1123– 1134 (2006). 16205776

In the paper

“The LC is the sole source of noradrenergic innervation to the central nervous system, best known for its role in arousal and vigilance, but more broadly thought to be recruited to combat environmental challenges84,85.”

What the sources say

• Not checked yetcites [84] Berridge CW & Waterhouse BD The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res. Brain Res. Rev. 42, 33– 84 (2003). 12668290 source
• Not checked yetcites [85] Sara SJ & Bouret S. Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron 76, 130– 141 (2012). 23040811

In the paper

“along with a reduction in exploratory behavior and an increase in self-grooming55–57.”

What the sources say

• Not checked yetcites [55] Hilakivi LA, Ota M. & Lister RG Effect of isolation on brain monoamines and the behavior of mice in tests of exploration, locomotion, anxiety and behavioral ‘despair’. Pharmacol. Biochem. Behav. 33, 371– 374 (1989). 2479036
• Not checked yetcites [56] Hol T. & Spruijt BM The MSH/ACTH(4–9) analog Org2766 counteracts isolation-induced enhanced social behavior via the amygdala. Peptides 13, 541– 544 (1992). 1326104
• Not checked yetcites [57] Vanderschuren LJ, Stein EA, Wiegant VM & Van Ree JM Social isolation and social interaction alter regional brain opioid receptor binding in rats. Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol. 5, 119– 127 (1995). 7549454

In the paper

“a 24-hour isolation in adult rats decreased CRF mRNA and protein in the PVN75 and decreased cortical CRF1 receptor levels81.”

What the sources say

• Not checked yetcites [75] Armando I, Volpi S, Aguilera G. & Saavedra JM Angiotensin II AT1 receptor blockade prevents the hypothalamic corticotropin-releasing factor response to isolation stress. Brain Res. 1142, 92– 99 (2007). 17306778 PMC2682713
• Not checked yetcites [81] Saavedra JM A Centrally Acting, Anxiolytic Angiotensin II AT1 Receptor Antagonist Prevents the Isolation Stress-Induced Decrease in Cortical CRF1 Receptor and Benzodiazepine Binding. Neuropsychopharmacology 31, 1123– 1134 (2006). 16205776

In the paper

“CRF-producing neurons are also widely distributed in extrahypothalamic regions, including the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), nucleus accumbens (NAc), and hippocampus77–79, which have, likewise, been implicated in the behavioral and physiological responses to stress.”

What the sources say

• Not checked yetcites [77] Deussing JM & Chen A. The Corticotropin-Releasing Factor Family: Physiology of the Stress Response. Physiol. Rev. 98, 2225– 2286 (2018). 30109816
• Not checked yetcites [78] Peng J. A Quantitative Analysis of the Distribution of CRH Neurons in Whole Mouse Brain. Front. Neuroanat. 11, (2017). PMC5524767 28790896
• Not checked yetcites [79] Swanson LW, Sawchenko PE, Rivier J. & Vale WW Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36, 165– 186 (1983). 6601247 source

In the paper

“Considering the potential for mixed selectivity, the recent observation that activation of DRN dopamine neurons not only increases social preference118 but can promote antinociception117 could be reconciled in a number of ways.”

What the sources say

• Not checked yetcites [118] Matthews GA Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell 164, 617– 631 (2016). 26871628 PMC4752823
• Not checked yetcites [117] Li C. Mu Opioid Receptor Modulation of Dopamine Neurons in the Periaqueductal Gray/Dorsal Raphe: A Role in Regulation of Pain. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 41, 2122– 2132 (2016). PMC4908643 26792442

In the paper

“Social isolation may recruit this response to appropriately prepare an individual for the susceptibilities of being alone, which might include an increased need for a rapid inflammatory response to combat bacterial infections sustained through physical injury, but the reduced need for protection against socially transmitted viral infections15,176.”

What the sources say

• Not checked yetcites [15] Eisenberger NI & Cole SW Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nat. Neurosci. 15, 669– 674 (2012). 22504347 source
• Not checked yetcites [176] Cole SW Human Social Genomics. PLOS Genet. 10, e1004601 (2014). PMC4148225 25166010 source

In the paper

“Taken together, these findings illustrate the existence of multiple mechanisms through which DRN dopamine neurons may limit the vulnerabilities of being alone: increasing social motivation, promoting vigilance/arousal, and enhancing responsivity to aversive stimuli.”

In the paper

“Furthermore, activation of BLA input to the ventral hippocampus or mPFC not only induces robust anxiety-like behavior in exploratory assays but also suppress social investigation in the resident–intruder assay184–186.”

What the sources say

• Not checked yetcites [184] Felix-Ortiz AC & Tye KM Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. J. Neurosci. Off. J. Soc. Neurosci. 34, 586– 595 (2014). PMC3870937 24403157
• Not checked yetcites [185] Felix-Ortiz AC BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79, 658– 664 (2013). 23972595 PMC4205569
• Not checked yetcites [186] Felix-Ortiz AC, Burgos-Robles A, Bhagat ND, Leppla CA & Tye KM Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex. Neuroscience 321, 197– 209 (2016). 26204817 PMC4721937

In the paper

“However, these neurons are also responsive to other salient stimuli, including palatable food and unexpected foot shock, and show greater activity during wakefulness compared with sleep, suggesting an arousal-promoting function112,115,188.”

What the sources say

• Not checked yetcites [112] Cho JR Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli. Neuron 94, 1205–1219.e8 (2017). 28602690 source
• Not checked yetcites [115] Groessl F. Dorsal tegmental dopamine neurons gate associative learning of fear. Nat. Neurosci. 21, 952– 962 (2018). 29950668 PMC6166775
• Not checked yetcites [188] Lu J, Jhou TC & Saper CB Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J. Neurosci. Off. J. Soc. Neurosci. 26, 193– 202 (2006). PMC6674316 16399687

In the paper

“In accordance with this notion, an emerging hypothesis posits that social and physical pain are processed by overlapping neural circuitry189.”

What the sources say

• Not checked yetcites [189] Eisenberger NI The pain of social disconnection: examining the shared neural underpinnings of physical and social pain. Nat. Rev. Neurosci. (2012). doi: 10.1038/nrn3231 22551663 source

In the paper

“Perturbations in social behavior are often, but not always, co-expressed with anxiety-related behaviors, and there is significant overlap in underlying neural correlates, which suggests a tight relationship between these two forms of behavioral expression58,187.”

What the sources say

• Not checked yetcites [58] Calhoon GG & Tye KM Resolving the neural circuits of anxiety. Nat. Neurosci. 18, 1394– 1404 (2015). 26404714 PMC7575249
• Not checked yetcites [187] Allsop SA, Weele V, M C, Wichmann R. & Tye KM Optogenetic insights on the relationship between anxiety-related behaviors and social deficits. Front. Behav. Neurosci. 8, (2014). PMC4099964 25076878

In the paper

“Monitoring fluorescent calcium activity in vivo revealed that these neurons are active in response to social stimuli, and this activity is heightened following acute isolation118.”

What the sources say

• Not checked yetcites [118] Matthews GA Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell 164, 617– 631 (2016). 26871628 PMC4752823

In the paper

“This is supported by human imaging studies revealing that social disconnection engages brain regions including the dorsal anterior cingulate cortex and anterior insula cortex190, which also process the affective component of physical pain191.”

What the sources say

• Not checked yetcites [190] Eisenberger NI, Lieberman MD & Williams KD Does Rejection Hurt? An fMRI Study of Social Exclusion. Science 302, 290– 292 (2003). 14551436 source
• Not checked yetcites [191] Price DD Psychological and Neural Mechanisms of the Affective Dimension of Pain. Science 288, 1769– 1772 (2000). 10846154 source

In the paper

“Given that ATII signaling can drive HPA axis activity, these data suggest that hypernatremia concomitantly suppresses activity within stress-related circuitry, while promoting activity in social reward-related oxytocin pathways, thereby inhibiting stress/anxiety-related behavior and facilitating social interaction.”

What the sources say

• Not checked yetcites [170] Krause EG Hydration state controls stress responsiveness and social behavior. J. Neurosci. Off. J. Soc. Neurosci. 31, 5470– 5476 (2011). PMC3086063 21471383

In the paper

“This scenario would predict that certain nodes in a social homeostatic network display “mixed selectivity,” similar to neurons underlying other complex cognitive processes181.”

What the sources say

• Not checked yetcites [181] Rigotti M. The importance of mixed selectivity in complex cognitive tasks. Nature 497, 585– 590 (2013). 23685452 PMC4412347

In the paper

“Immune system changes can also predict subsequent loneliness, suggesting a reciprocal relationship between these two phenomena64.”

What the sources say

• Not checked yetcites [64] Cole SW Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Proc. Natl. Acad. Sci. 112, 15142– 15147 (2015). 26598672 PMC4679065 source

In the paper

“Specifically, the agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are essential in the maintenance of energy balance, and their activity rapidly drives feeding behavior in a state of hunger173.”

What the sources say

• Not checked yetcites [173] Krashes MJ Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Invest. 121, 1424– 1428 (2011). 21364278 PMC3069789 source

In the paper

“This immune response also appears to be recruited in a state of perceived isolation—humans with high self-reported loneliness show enhanced proinflammatory activity but reduced antiviral response66,177–179.”

What the sources say

• Not checked yetcites [66] Pressman SD Loneliness, social network size, and immune response to influenza vaccination in college freshmen. Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc. 24, 297– 306 (2005). 15898866 source
• Not checked yetcites [177] Cole SW Social regulation of gene expression in human leukocytes. Genome Biol. 8, R189 (2007). PMC2375027 17854483 source
• Not checked yetcites [178] Creswell JD Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain. Behav. Immun. 26, 1095– 1101 (2012). 22820409 PMC3635809 source
• Not checked yetcites [179] Glaser R, Kiecolt-Glaser JK, Speicher CE & Holliday JE Stress, loneliness, and changes in herpesvirus latency. J. Behav. Med. 8, 249– 260 (1985). 3003360

In the paper

“Intriguingly, acute hypernatremia in rats is also associated with increased plasma oxytocin, increased c-Fos expression in magnocellular PVN oxytocin neurons, and suppression of ATII production170.”

What the sources say

• Not checked yetcites [170] Krause EG Hydration state controls stress responsiveness and social behavior. J. Neurosci. Off. J. Soc. Neurosci. 31, 5470– 5476 (2011). PMC3086063 21471383

In the paper

“Optogenetic activation of these neurons promoted social preference and real-time place avoidance, whereas inhibition reduced isolation-induced social preference.”

What the sources say

• Not checked yetcites [118] Matthews GA Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell 164, 617– 631 (2016). 26871628 PMC4752823

In the paper

“However, it has been reasoned that emotions constitute an internal state, encoded by specific neural circuits, which can give rise to externally observable behaviors150.”

What the sources say

• Not checked yetcites [150] Anderson DJ & Adolphs R. A Framework for Studying Emotions Across Phylogeny. Cell 157, 187– 200 (2014). 24679535 PMC4098837

In the paper

“Indeed, specialized circuits, within discrete hypothalamic nuclei, underlie the expression of parental behavior211, aggression212, male intruder-specific behavior213, opposite sex approach,214 and mating212.”

What the sources say

• Not checked yetcites [211] Wu Z, Autry AE, Bergan JF, Watabe-Uchida M. & Dulac CG Galanin neurons in the medial preoptic area govern parental behavior. Nature 509, 325– 330 (2014). 24828191 PMC4105201
• Not checked yetcites [212] Lin D. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221– 226 (2011). 21307935 PMC3075820 source
• Not checked yetcites [213] Soden ME Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior. Cell Rep. 16, 304– 313 (2016). 27346361 PMC4945459
• Not checked yetcites [214] McHenry JA Hormonal gain control of a medial preoptic area social reward circuit. Nat. Neurosci. 20, 449– 458 (2017). 28135243 PMC5735833

In the paper

“Grouped living can lead to the establishment of social hierarchies in multiple species including fish, birds, rodents, and primates201–204.”

What the sources say

• Not checked yetcites [201] Grosenick L, Clement TS & Fernald RD Fish can infer social rank by observation alone. Nature 445, 429– 432 (2007). 17251980
• Not checked yetcites [202] Morgan D. Predictors of social status in cynomolgus monkeys (Macaca fascicularis) after group formation. Am. J. Primatol. 52, 115– 131 (2000). 11078026
• Not checked yetcites [203] Schjelderup-Ebbe T. Beiträge zur Sozialpsychologie des Haushuhns. [Observation on the social psychology of domestic fowls.]. Z. Für Psychol. Physiol. Sinnesorgane Abt 1 Z. Für Psychol. 88, 225– 252 (1922).
• Not checked yetcites [204] Uhrich J. The social hierarchy in albino mice. J. Comp. Psychol. 25, 373– 413 (1938).

In the paper

“These findings include differences between subordinates and dominants in CRF expression in the BNST, CeA, MeA, and mPOA206, mitochondrial function and dopamine signaling in the NAc207,208, and glutamatergic synaptic strength in the mPFC209.”

What the sources say

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• Not checked yetcites [207] Hollis F. Mitochondrial function in the brain links anxiety with social subordination. Proc. Natl. Acad. Sci. 112, 15486– 15491 (2015). 26621716 PMC4687564
• Not checked yetcites [208] Jupp B. Social dominance in rats: Effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum. Psychopharmacology (Berl.) 233, 579– 589 (2016). 26554388 PMC4726718
• Not checked yetcites [209] Wang F. Bidirectional Control of Social Hierarchy by Synaptic Efficacy in Medial Prefrontal Cortex. Science 334, 693– 697 (2011). 21960531

In the paper

“This dual role of DRN dopamine neurons also points towards a potential mechanism through which acute isolation reduces pain perception157,158.”

What the sources say

• Not checked yetcites [157] Naranjo JR & Fuentes JA Association between hypoalgesia and hypertension in rats after short-term isolation. Neuropharmacology 24, 167– 171 (1985). 3990918
• Not checked yetcites [158] Konecka AM & Sroczynska I. Stressors and pain sensitivity in CFW mice. Role of opioid peptides. Arch. Int. Physiol. Biochim. 98, 245– 252 (1990). 1708992

In the paper

“Although subordination in animal societies is not always directly related to low social connectedness or unmet social needs, social rank bestows variability in subjective social experience without removing support structure for safety, warmth and other nonsocial benefits of a group.”

In the paper

“While this process can be adaptive and introduces greater flexibility into homeostatic regulation, it also passes an element of control to the individual, taking homeostatic regulation beyond purely automatic mechanisms200.”

What the sources say

• Not checked yetcites [200] Damasio A. & Damasio H. Exploring the concept of homeostasis and considering its implications for economics. J. Econ. Behav. Organ. 126, 125– 129 (2016).

In the paper

“Consistent with this, loneliness—independent of social network size—is associated with higher mortality13,193 increased blood pressure11,194, higher rate of diabetes, hypertension, arthritis, emphysema195, and Alzheimer’s disease196, along with poor health habits stemming from a lack of self-control197,198.”

What the sources say

• Not checked yetcites [11] Hawkley LC, Masi CM, Berry JD & Cacioppo JT Loneliness is a unique predictor of age-related differences in systolic blood pressure. Psychol. Aging 21, 152– 164 (2006). 16594800 source
• Not checked yetcites [194] Hawkley LC, Thisted RA, Masi CM & Cacioppo JT Loneliness predicts increased blood pressure: 5-year cross-lagged analyses in middle-aged and older adults. Psychol. Aging 25, 132– 141 (2010). 20230134 PMC2841310 source
• Not checked yetcites [195] Tomaka J, Thompson S. & Palacios R. The relation of social isolation, loneliness, and social support to disease outcomes among the elderly. J. Aging Health 18, 359– 384 (2006). 16648391
• Not checked yetcites [196] Wilson RS Loneliness and risk of Alzheimer disease. Arch. Gen. Psychiatry 64, 234– 240 (2007). 17283291 source
• Not checked yetcites [197] Baumeister RF, Nathan C, Ciarocco NJ & Twenge JM Social Exclusion Impairs Self-Regulation. J. Pers. Soc. Psychol. 88, 589– 604 (2005). 15796662
• Not checked yetcites [198] DeWall CN, Baumeister RF & Vohs KD Satiated with Belongingness? Effects of Acceptance, Rejection, and Task Framing on Self-Regulatory Performance. J. Pers. Soc. Psychol. 95, 1367– 1382 (2008). 19025289 PMC2597411

In the paper

“Most recently, “winning”-induced plasticity in the tube test was localized to a mediodorsal thalamic (MDT) projection to the dorsomedial PFC (dmPFC), as phasic optogenetic stimulation of the dmPFC, or the MDT–dmPFC projection, immediately induced winning against a previously dominant cagemate210.”

What the sources say

• Not checked yetcites [210] Zhou T. History of winning remodels thalamo-PFC circuit to reinforce social dominance. Science 357, 162– 168 (2017). 28706064

In the paper

“Homeostatic feelings act as “informative regulatory interfaces”—providing means for an animal to sense its physiological state and guaranteeing attention to relevant stimuli200.”

What the sources say

• Not checked yetcites [200] Damasio A. & Damasio H. Exploring the concept of homeostasis and considering its implications for economics. J. Econ. Behav. Organ. 126, 125– 129 (2016).

In the paper

“However, AgRP activity is rapidly suppressed on sensory detection of food227,228,230, which, surprisingly, suggests that ongoing AgRP activity is dispensable for food consumption.”

What the sources say

• Not checked yetcites [227] Betley JN Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180– 185 (2015). 25915020 PMC4567040 source
• Not checked yetcites [228] Mandelblat-Cerf Y. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife (2015). doi: 10.7554/eLife.07122 PMC4498165 26159614 source
• Not checked yetcites [230] Chen Y, Lin Y-C, Kuo T-W & Knight ZA Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits. Cell 160, 829– 841 (2015). 25703096 PMC4373539 source

In the paper

“A potentially similar function has been described for arcuate nucleus AgRP neurons and nitric oxide synthase 1 (NOS1) neurons in the subfornical organ (SFO). These neurons show heightened activity during hunger (AgRP) and thirst (NOS1), their activity elicits an aversive state (place avoidance), and they are essential for driving feeding and drinking behaviors, respectively21,227.”

What the sources say

• Not checked yetcites [21] Zimmerman CA Thirst neurons anticipate the homeostatic consequences of eating and drinking. Nature 537, 680– 684 (2016). 27487211 PMC5161740 source
• Not checked yetcites [227] Betley JN Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180– 185 (2015). 25915020 PMC4567040 source

In the paper

“Furthermore, mice performed operant responses to stimulate AgRP neurons in the presence, but not the absence of food, suggesting that AgRP activity can be positively reinforcing231.”

What the sources say

• Not checked yetcites [231] Chen Y, Lin Y-C, Zimmerman CA, Essner RA & Knight ZA Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife (2016). doi: 10.7554/eLife.18640 PMC5016090 27554486

In the paper

“AgRP neurons are activated in a state of energy deficit228, and their optical stimulation can voraciously promote food consumption, but also elicits real-time place avoidance (indicative of an aversive state) in the absence of food173,227,229.”

What the sources say

• Not checked yetcites [228] Mandelblat-Cerf Y. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife (2015). doi: 10.7554/eLife.07122 PMC4498165 26159614 source
• Not checked yetcites [173] Krashes MJ Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Invest. 121, 1424– 1428 (2011). 21364278 PMC3069789 source
• Not checked yetcites [227] Betley JN Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180– 185 (2015). 25915020 PMC4567040 source
• Not checked yetcites [229] Aponte Y, Atasoy D. & Sternson SM AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat. Neurosci. 14, 351– 355 (2011). 21209617 PMC3049940

In the paper

“If we conceptualize these as discrete “effector systems,” then this raises the possibility that decentralized processing of different social “needs” may occur in separable nodes215.”

What the sources say

• Not checked yetcites [215] Swan M. Blockchain Thinking: The Brain as a Decentralized Autonomous Corporation [Commentary]. IEEE Technol. Soc. Mag. 34, 41– 52 (2015).

In the paper

“In support of this concept, functional magnetic resonance imaging in humans has revealed that more lonely individuals show greater activation of the ventral striatum in response to familiar social cues223, but contrastingly reduced activation in response to unfamiliar social cues224.”

What the sources say

• Not checked yetcites [223] Inagaki TK Yearning for connection? Loneliness is associated with increased ventral striatum activity to close others. Soc. Cogn. Affect. Neurosci. nsv076 (2015). doi: 10.1093/scan/nsv076 PMC4927031 26084531
• Not checked yetcites [224] Cacioppo JT, Norris CJ, Decety J, Monteleone G. & Nusbaum H. In the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. J. Cogn. Neurosci. 21, 83– 92 (2009). 18476760 PMC2810252 source

In the paper

“Therefore, an alternative hypothesis proposes that AgRP activity provides a sustained positive valence signal, that potentiates the incentive value of food, and supports transition from foraging to feeding behavior via persistent changes in downstream circuitry231.”

What the sources say

• Not checked yetcites [231] Chen Y, Lin Y-C, Zimmerman CA, Essner RA & Knight ZA Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife (2016). doi: 10.7554/eLife.18640 PMC5016090 27554486

In the paper

“However, while mechanistic differences exist, the neural systems mediating homeostatic and hedonic feeding are proposed to be intertwined, and highly overlapping with reward circuitry217,218.”

What the sources say

• Not checked yetcites [217] Rossi MA & Stuber GD Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Cell Metab. 27, 42– 56 (2018). 29107504 PMC5762260
• Not checked yetcites [218] Castro DC, Cole SL & Berridge KC Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry. Front. Syst. Neurosci. 9, (2015). PMC4466441 26124708

In the paper

“Motivated behaviors regulating food intake are often distinguished as homeostatic (essential for maintaining energy balance and survival) or hedonic (driven by sensory perception or pleasure in the absence of a need state)217.”

What the sources say

• Not checked yetcites [217] Rossi MA & Stuber GD Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Cell Metab. 27, 42– 56 (2018). 29107504 PMC5762260

In the paper

“However, an important consideration for social behavior is that (unlike food detection) initial social contact does not necessarily guarantee a rewarding social experience. Therefore immediate suppression of neural activity on social contact may be inappropriate for DRN dopamine neurons, and activity may persist until a stable relationship has been achieved.”