Cellular imaging may reveal the neuronal basis of social motivation and how it can be disrupted

Zoe Donaldson, Ph.D.

University of Colorado Boulder

Funded in September, 2018: $200000 for 3 years
LAY SUMMARY . ABSTRACT .

LAY SUMMARY

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Cellular imaging may reveal the neuronal basis of social motivation and how it can be disrupted

This animal study will examine the biological basis of social motivation and how it is disrupted in various attachment disorders. Investigators will use 3-D calcium imaging and “optogenetics” (which manipulates specific neurons through light) in freely moving monogamous prairie vole pairs that have life-long bonds with one another. They will identify neuronal activity implicated in social motivation and how the “bonding” hormone oxytocin affects this activity.

 They found in prior studies that a subset of neurons in reward regions the animals’ brain is active before a prairie vole is reunited with its partner, suggesting that this is a marker of social motivation. They hypothesize that these neurons are sensitive to the hormone oxytocin, which is required for forming social bonds, and that decreased oxytocin adversely affects the social motivation involved in forming those bonds. They will test the hypothesis by determining whether blocking oxytocin alters the neurons’ activity and the animals’ social motivation. To do this, they will apply newly developed 3-D calcium imaging that was created by senior investigators supported under the NIH BRAIN Initiative.

They will study prairie voles that press a lever to reunite with their mate. They first will use 3-D calcium imaging as the voles press a lever to seek out their partner.  The investigators will see if the neurons in the reward regions of the brain are involved in encoding the social motivation that drives this activity. Then they will use optogenetics to stimulate those neurons and see whether their lever-pressing intensifies. Thereafter, they will use a drug that blocks oxytocin and see whether the motivation-associated, lever-pressing activity in these neurons decreases. If so, the study will provide evidence suggesting the neuronal basis of social motivation and demonstrate oxytocin’s pivotal role on those neurons.  

ABSTRACT

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Cellular imaging may reveal the neuronal basis of social motivation and how it can be disrupted

The formation and loss of social bonds dramatically influence human health, but the fundamental biological processes that cement these bonds over time and how these processes are engaged in mental illness or following loss remains poorly understood. In this project, I will use monogamous prairie voles to identify the neurons that control the motivation to be with a pair-bonded partner and ask whether pharmacological manipulations of oxytocin, a hormone required for bond formation, alters social motivation and activity within these cells. My lab has identified a subset of neurons in the prairie vole nucleus accumbens whose activity precedes reunion with a partner. To test the hypothesis that these neurons represent an oxytocin-sensitive substrate underlying social motivation, we will undertake three experiments. First, we will use in vivo Ca2+ imaging to determine whether the same neurons are active when a prairie vole is lever-pressing to gain access to its absent partner. Next, using advanced spatially-shaped optogenetic approaches, we will ask whether activation of these neurons stimulates lever pressing. Finally, we will ask whether blockade of oxytocin signaling reduces social motivation and alters motivation-associated activity within these cells. Completion of these experiments will provide fundamental insights into the neuronal basis of social motivation, elucidating a physical substrate that must be remodeled in order to successfully adapt to the loss of a bond and to treat disorders characterized by over-attachment, such as separation anxiety disorders. Likewise, we will directly address whether modulation of oxytocin systems represents a potential therapeutic intervention. A positive results from our experiments would pave a clear path towards novel oxytocin-based treatments for over-attachment and the maladaptive impacts of social loss.

INVESTIGATOR BIOGRAPHIES

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Zoe Donaldson, Ph.D.

Zoe Donaldson is an Assistant Professor in the Departments of Molecular, Cellular and Developmental Biology and Psychology and Neuroscience at the University of Colorado Boulder. Dr. Donaldson received her B.S. from University of California Los Angeles, and received her Ph.D. as an HHMI Predoctoral Fellow in the laboratory of Dr. Larry Young at Emory University, where she investigated the genetic mechanisms that contribute to sociobehavioral diversity. She then joined the laboratories of René Hen and Frances Champagne at Columbia University as a Robert Wood Johnson Health & Society Scholar, where she studied the developmental sensitive periods and genetic variation underlying anxiety and depression-related traits.  At the University of Colorado Boulder, her lab pioneers molecular-genetic tools in monogamous prairie voles to identify the neural and genetic basis of complex social behaviors, including social bond formation and the response to loss. In addition to funding from the Dana Foundation, the Donaldson lab is supported by the NIH Director’s New Innovator Award, the Whitehall Foundation, a National Science Foundation EDGE award, and an NIH Pathway to Independence Award.   

KEYWORDS


Anatomy: Basal ganglia

Neuropeptides
Conditions: Autism
Social Phobia
Function: Animal research
Brain and behavior
Technology:
Neuropharmacology