Neurobiology of Loneliness, Isolation, and Loss: Integrating Human and Animal Perspectives

Frontiers in Behavioral Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: April 8, 2022

In social species such as humans, non-human primates, and even many rodent species, interaction the maintenance of bonds are necessary for mental physical health wellbeing. perceived isolation, or loneliness, is not only characterized by isolation from peers loved ones, but also involves negative perceptions about interactions connectedness that reinforce feelings anxiety. As a complex behavioral state, it no surprise loneliness associated with dysfunction within ventral striatum limbic system – brain regions regulate motivation stress responsiveness, respectively. Accompanying these neural changes physiological symptoms increased plasma urinary cortisol levels an increase in responsivity. Although studies using animal models perfectly analogous to uniquely human state on effects animals have observed similar corticosterone, analog cortisol, display altered motivation, dysregulation mesocortical dopamine systems. This review will discuss neuropsychological components models, neurochemical regulators phenotypes neuroanatomical focus corticostriatal We loss unique form consequences bond disruption stress-related behavior neurophysiology.

Language: Английский

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Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles

Current Biology, Journal Year: 2022, Volume and Issue: 32(5), P. 1026 - 1037.e4

Published: Feb. 1, 2022

Language: Английский

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Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 28, 2023

The loss of a spouse is often cited as the most traumatic event in person’s life. However, for people, severity grief and its maladaptive effects subside over time via an understudied adaptive process. Like humans, socially monogamous prairie voles ( Microtus ochrogaster ) form opposite-sex pair bonds, upon partner separation, show stress phenotypes that diminish time. We test hypothesis extended separation diminishes bond-associated behaviors causes bond transcriptional signatures to erode. Opposite-sex or same-sex paired males were cohoused 2 weeks then either remained separated 48 hours 4 before collecting fresh nucleus accumbens tissue RNAseq. In separate cohort, we assessed partner-directed affiliation at these points. found persist despite prolonged both voles. bonding led changes accumbal transcription stably maintained while animals but eroded following separation. Eroded genes are associated with gliogenesis myelination, suggesting previously undescribed role glia loss. Further, pioneered neuron-specific translating ribosomal affinity purification Neuronally enriched revealed dopaminergic-, mitochondrial-, steroid hormone signaling-associated gene clusters sensitive acute disruption adaptation. Our results suggest erodes transcriptomic core behavioral features remaining intact, revealing potential molecular processes priming vole be able new bond.

Language: Английский

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Cholinergic interneurons in the nucleus accumbens are a site of cellular convergence for corticotropin‐releasing factor and estrogen regulation in male and female mice

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(5), P. 4937 - 4953

Published: July 30, 2024

Cholinergic interneurons (ChIs) act as master regulators of striatal output, finely tuning neurotransmission to control motivated behaviours. ChIs are a cellular target many peptide and hormonal neuromodulators, including corticotropin-releasing factor, opioids, insulin leptin, which can influence an animal's behaviour by signalling stress, pleasure, pain nutritional status. However, little is known about how sex hormones via estrogen receptors the function these other neuromodulators. Here, we performed in situ hybridisation on mouse tissue characterise effect choline acetyltransferase (Chat), receptor alpha (Esr1) factor type 1 (Crhr1) expression. Although did not detect differences ChAT protein levels dorsal striatum or nucleus accumbens, found that female mice have more Chat mRNA-expressing neurons than males both accumbens. At population level, observed sexually dimorphic distribution Esr1- Crhr1-expressing ventral was negatively correlated intact females, abolished ovariectomy present males. Only NAc find significant co-express Crhr1 Esr1 females lesser extent transcript were only during estrus phase indicating changes hormone modulate interaction between mRNA levels.

Language: Английский

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Oxytocin and Dopamine Receptor Expression: Cellular Level Implications for Pair Bonding

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Oxytocin ( Oxtr ) and dopamine Drd1 , Drd2 receptors provide a canonical example for how differences in neuromodulatory drive individual species-level behavioral variation. These systems exhibit striking functionally-relevant nucleus accumbens (NAc) expression across monogamous prairie voles Microtus ochrogaster promiscuous meadow pennsylvanicus ). However, their cellular organization remains largely unknown. Using multiplex situ hybridization, we mapped sexually naïve mate-paired voles. Prairie have more Oxtr+ cells than voles, but distribution dopamine-receptor cell class was similar, indicating general upregulation rather bias. enriched that express both Drd1+/Drd2+ suggesting these may be particularly sensitive to oxytocin. We found no species or pairing-induced Drd1+ Drd2+ counts, prior reports of reflect already expressing receptors. Finally, used single-nucleus sequencing the first comprehensive map Drd1-5 molecularly-defined NAc types vole. results critical framework understanding nonapeptide catecholamine recruit distinct shape social behavior.

Language: Английский

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Reciprocal processes of sensory perception and social bonding: an integrated social‐sensory framework of social behavior

Genes Brain & Behavior, Journal Year: 2021, Volume and Issue: 21(3)

Published: Dec. 14, 2021

Abstract Organisms filter the complexity of natural stimuli through their individual sensory and perceptual systems. Such filtering is particularly important for social stimuli. A shared “social umwelt” allows individuals to respond appropriately expected diversity cues signals during interactions. In this way, behavioral neurobiological mechanisms sociality bonding cannot be disentangled from processing. While a degree embeddedness between processes clear, our dominant theoretical frameworks favor treating as distinct. An integrated social‐sensory framework has potential greatly expand understanding underlying variation in more broadly. Here we leverage what known about processing pair two common study systems with significant species differences umwelt (rodent chemosensation avian acoustic communication). We primarily highlight that (1) communication essential bond formation maintenance, (2) neural circuits perception, are integrated, (3) candidate neuromodulatory regulate also impact perception. Finally, propose approaches fully integrate processing, communication, across levels analysis: behavioral, neurobiological, genomic. This perspective raises key questions: how shaped by processing?, extent saliency interactions emerging relationships?

Language: Английский

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Partner separation rescues pair bond-induced decreases in hypothalamic oxytocin neural densities

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 24, 2023

Studies in prairie voles (Microtus ochrogaster) have shown that although formation of the pair bond is accompanied by a suite behavioral changes, between two can dissolve and individuals form new bonds with other conspecifics. However, neural mechanisms underlying this flexibility not been well-studied. Here we examine plasticity nonapeptide, vasopressin (VP) oxytocin (OT), neuronal populations relation to bonding dissolution bonds. Using adult male female voles, animals were either bonded, co-housed same-sex sibling, separated from their partner, or sibling. We examined densities VP OT cell groups observed nonapeptide paraventricular nucleus hypothalamus (PVN). Voles bonded had fewer PVN neurons, suggesting decrease bonding, but increase return pre-pair baseline after bond. Our findings suggest are particularly plastic adulthood, providing mechanism which exhibit context-appropriate behavior related status.

Language: Английский

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Single nucleus RNA-sequencing reveals transcriptional synchrony across different relationships

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

As relationships mature, partners share common goals, improve their ability to work together, and experience coordinated emotions. However, the neural underpinnings responsible for this unique, pair-specific remain largely unexplored. Here, we used single nucleus RNA-sequencing examine transcriptional landscape of accumbens (NAc) in socially monogamous prairie voles peer or mating-based relationships. We show that, regardless pairing type, exhibit synchrony with a partner. Further, identify genes expressed oligodendrocyte progenitor cells that are synchronized between partners, correlated dyadic behavior, sensitive partner separation. Together, our data indicate social environment profoundly shapes transcription NAc. This provides potential biological mechanism by which shared reinforces strengthens

Language: Английский

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Prairie voles as a model for adaptive reward remodeling following loss of a bonded partner

Annals of the New York Academy of Sciences, Journal Year: 2024, Volume and Issue: 1535(1), P. 20 - 30

Published: April 9, 2024

Loss of a loved one is painful event that substantially elevates the risk for physical and mental illness impaired daily function. Socially monogamous prairie voles are laboratory-amenable rodents form life-long pair bonds exhibit distress upon partner separation, mirroring phenotypes seen in humans. These attributes make an excellent model studying biology loss. In this review, we highlight parallels between humans voles, focusing on reward system engagement during bonding As yearning unique feature differentiates loss from other negative states, posit which homeostatic mechanisms help to maintain disrupted loss, resulting impacts. Finally, synthesize studies delineate remodeling systems adaptation. The stalling these processes likely contributes prolonged grief disorder, diagnosis recently added Diagnostic Statistical Manual Psychiatry.

Language: Английский

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Attachment across the lifespan: Examining the intersection of pair bonding neurobiology and healthy aging

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 153, P. 105339 - 105339

Published: Aug. 2, 2023

Language: Английский

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