Natural Neural Projection Dynamics Underlying Social Behavior

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Jun 21

PMID 24949967

Citations 695

Authors

Lisa A Gunaydin

Logan Grosenick

Joel C Finkelstein

Isaac V Kauvar

Lief E Fenno

Avishek Adhikari

Stephan Lammel

Julie J Mirzabekov

Raag D Airan

Kelly A Zalocusky

Kay M Tye

Polina Anikeeva

Robert C Malenka

Karl Deisseroth

Affiliations

Soon will be listed here.

Abstract

Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.

Citing Articles

A statistical framework for analysis of trial-level temporal dynamics in fiber photometry experiments.

Loewinger G, Cui E, Lovinger D, Pereira F Elife. 2025; 13.

PMID: 40073228 PMC: 11903033. DOI: 10.7554/eLife.95802.

Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner.

Zhao X, Chae Y, Smith D, Chen V, DeFelipe D, Sokol J Elife. 2025; 13.

PMID: 40035330 PMC: 11879111. DOI: 10.7554/eLife.94924.

A hypothalamic circuit underlying the dynamic control of social homeostasis.

Liu D, Rahman M, Johnson A, Amo R, Tsutsui-Kimura I, Sullivan Z Nature. 2025; .

PMID: 40011768 DOI: 10.1038/s41586-025-08617-8.

Early Life Stress Impairs VTA Coordination of BLA Network and Behavioral States.

Stone B, Antonoudiou P, Teboul E, Scarpa G, Weiss G, Maguire J J Neurosci. 2025; 45(11).

PMID: 39947924 PMC: 11905350. DOI: 10.1523/JNEUROSCI.0088-24.2025.

Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse.

Galiza Soares J, Sutley-Koury S, Pomrenze M, Tucciarone J Front Neuroanat. 2025; 18:1521016.

PMID: 39917739 PMC: 11798945. DOI: 10.3389/fnana.2024.1521016.

References

Aravanis A, Wang L, Zhang F, Meltzer L, Mogri M, Schneider M . An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng. 2007; 4(3):S143-56. DOI: 10.1088/1741-2560/4/3/S02. View

Young L, Wang Z . The neurobiology of pair bonding. Nat Neurosci. 2004; 7(10):1048-54. DOI: 10.1038/nn1327. View

Brischoux F, Chakraborty S, Brierley D, Ungless M . Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc Natl Acad Sci U S A. 2009; 106(12):4894-9. PMC: 2660746. DOI: 10.1073/pnas.0811507106. View

Podda M, Riccardi E, DAscenzo M, Azzena G, Grassi C . Dopamine D1-like receptor activation depolarizes medium spiny neurons of the mouse nucleus accumbens by inhibiting inwardly rectifying K+ currents through a cAMP-dependent protein kinase A-independent mechanism. Neuroscience. 2010; 167(3):678-90. DOI: 10.1016/j.neuroscience.2010.02.075. View

Perez M, White F, Hu X . Dopamine D(2) receptor modulation of K(+) channel activity regulates excitability of nucleus accumbens neurons at different membrane potentials. J Neurophysiol. 2006; 96(5):2217-28. DOI: 10.1152/jn.00254.2006. View

Liu Y, Wang Z . Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles. Neuroscience. 2003; 121(3):537-44. DOI: 10.1016/s0306-4522(03)00555-4. View

Xu W, Sudhof T . A neural circuit for memory specificity and generalization. Science. 2013; 339(6125):1290-5. PMC: 3651700. DOI: 10.1126/science.1229534. View

Young L, Lim M, Gingrich B, Insel T . Cellular mechanisms of social attachment. Horm Behav. 2001; 40(2):133-8. DOI: 10.1006/hbeh.2001.1691. View

Moy S, Nadler J, Perez A, Barbaro R, Johns J, Magnuson T . Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004; 3(5):287-302. DOI: 10.1111/j.1601-1848.2004.00076.x. View

10.

Chaudhury D, Walsh J, Friedman A, Juarez B, Ku S, Koo J . Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature. 2012; 493(7433):532-6. PMC: 3554860. DOI: 10.1038/nature11713. View

11.

Budygin E, Park J, Bass C, Grinevich V, Bonin K, Wightman R . Aversive stimulus differentially triggers subsecond dopamine release in reward regions. Neuroscience. 2011; 201:331-7. PMC: 3258373. DOI: 10.1016/j.neuroscience.2011.10.056. View

12.

Dong Y, Li J, Zhang F, Li Y . Nociceptive afferents to the premotor neurons that send axons simultaneously to the facial and hypoglossal motoneurons by means of axon collaterals. PLoS One. 2011; 6(9):e25615. PMC: 3183065. DOI: 10.1371/journal.pone.0025615. View

13.

Yuan K, Shih J, Winer J, Schreiner C . Functional networks of parvalbumin-immunoreactive neurons in cat auditory cortex. J Neurosci. 2011; 31(37):13333-42. PMC: 3181135. DOI: 10.1523/JNEUROSCI.1000-11.2011. View

14.

Winslow J . Mouse social recognition and preference. Curr Protoc Neurosci. 2008; Chapter 8:Unit 8.16. DOI: 10.1002/0471142301.ns0816s22. View

15.

Robinson D, Zitzman D, Smith K, Spear L . Fast dopamine release events in the nucleus accumbens of early adolescent rats. Neuroscience. 2010; 176:296-307. PMC: 3061289. DOI: 10.1016/j.neuroscience.2010.12.016. View

16.

Kravitz A, Freeze B, Parker P, Kay K, Thwin M, Deisseroth K . Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010; 466(7306):622-6. PMC: 3552484. DOI: 10.1038/nature09159. View

17.

Robinson D, Heien M, Wightman R . Frequency of dopamine concentration transients increases in dorsal and ventral striatum of male rats during introduction of conspecifics. J Neurosci. 2002; 22(23):10477-86. PMC: 6758730. View

18.

Airan R, Thompson K, Fenno L, Bernstein H, Deisseroth K . Temporally precise in vivo control of intracellular signalling. Nature. 2009; 458(7241):1025-9. DOI: 10.1038/nature07926. View

19.

Imai K, Keele L, Tingley D . A general approach to causal mediation analysis. Psychol Methods. 2010; 15(4):309-34. DOI: 10.1037/a0020761. View

20.

Tsai H, Zhang F, Adamantidis A, Stuber G, Bonci A, De Lecea L . Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009; 324(5930):1080-4. PMC: 5262197. DOI: 10.1126/science.1168878. View