Characterization of fever-sensitive circuits and their effects on social behaviors in autism mouse models

  • Awarded: 2018
  • Award Type: Research
  • Award #: 572189

Social recognition is essential for individuals to survive, reproduce and raise their young. In humans, social recognition can be severely affected by mental illnesses and neurodevelopmental disorders, such as autism spectrum disorder (ASD). Interestingly, anecdotal reports from parents and professional caregivers suggest that children with ASD can exhibit improved social interactions during episodes of fever. Deciphering the unique characteristics of social recognition in animals and humans, and understanding how this behavior may be affected by external influences, are critical steps toward helping to treat individuals suffering from social behavior deficits.

Catherine Dulac is interested in understanding the molecular mechanisms and circuitry underlying the proper development and expression of social behaviors. Dulac’s laboratory previously uncovered functional neuronal circuits and specific hypothalamic neuron types regulating a variety of social behaviors1,2. As the neuronal circuits mediating social behaviors and thermoregulation are juxtaposed in the hypothalamus, this has led to a hypothesis that the hypothalamic neuromodulatory systems involved in the regulation of fever may also trigger the enhanced social cognition sometimes reported in individuals with ASD during fever periods.

Building on preliminary findings from a previous SFARI grant, Dulac’s group now aims to molecularly identify populations of neurons associated with fever states using state-of-the-art molecular profiling techniques and employing sophisticated behavioral approaches, including newly created machine learning algorithms, to determine how these neurons and neuronal circuits influence social behaviors. Finally, the researchers will assess behavioral changes in various mouse models for autism, including 16p11.2 deletion, Cntnap2 and Shank3b mutants, during febrile periods. The characterization of neural circuits controlling changes in behavior during fever is a critical step toward understanding how fever may affect ASD symptoms and, in turn, may inspire new strategies for therapeutic intervention.

References

1.Wu Z. et al. Nature 509, 325-330 (2014) PubMed
2.Kohl J. et al. Nature 556, 326-331 (2018) PubMed
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