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Peer-reviewedCC BY 4.0Nature Communications

Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors in mice

  • Michael W. Gongwer1,2,3
  • Fanny Etienne1
  • Eric N. Moca1
  • Sara V. Blagburn-Blanco1,2,3
  • Megan S. Chappell1,2
  • Keionna A. Newton1,2
  • Daniel T. Gray1
  • Jack P. Riley1
  • Chloe R. Christensen1
  • Russell N. Ahmed4
  • Alexander S. Enos1
  • Melody Haratian1
6 more authors
  • Alex Qi4
  • Rocio Rojo5,6
  • Scott A. Wilke4
  • Clare Pridans5
  • Laura A. DeNardo1
  • Lindsay M. De Biase1
6 affiliations
  1. 1Department of Physiology, University of California, Los Angeles, CA USA
  2. 2Neuroscience Interdepartmental Program, University of California, Los Angeles, CA USA
  3. 3UCLA Medical Scientist Training Program, University of California, Los Angeles, CA USA
  4. 4Department of Psychiatry, University of California, Los Angeles, CA USA
  5. 5Institution for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
  6. 6Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
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Abstract

While microglia are well known for pruning synapses during neurodevelopment, their role in synapse formation remains understudied. Here we investigate how microglial absence impacts synaptic development in the nucleus accumbens (NAc), a region critical for emotional regulation and motivated behaviors. Using genetically modified mice lacking microglia (Csf1rΔFIRE/ΔFIRE), we find blunted excitatory synapse formation in the NAc, particularly during the second and third postnatal weeks. Tissue-level NAc proteomics in the third postnatal week reveals changes in proteins involved in synapse structure, trans-synaptic signaling, and pre-synaptic function. Although electrophysiological changes largely resolve by adulthood, microglia-lacking mice exhibit persistent changes in threat avoidance behavior and underlying NAc neuronal activity. Transient depletion of NAc microglia during the second postnatal week similarly disrupts synapse formation and adult threat avoidance. Together, these findings identify a role for microglia in shaping NAc synaptic development and in establishing functional circuits that support adult behavioral function.

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Cite

BibTeXRIS
BibTeX
@article{gongwer2026microglia,
  title = {{Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors in mice}},
  author = {Michael W. Gongwer and Fanny Etienne and Eric N. Moca and Sara V. Blagburn-Blanco and Megan S. Chappell and Keionna A. Newton and Daniel T. Gray and Jack P. Riley and Chloe R. Christensen and Russell N. Ahmed and Alexander S. Enos and Melody Haratian and Alex Qi and Rocio Rojo and Scott A. Wilke and Clare Pridans and Laura A. DeNardo and Lindsay M. De Biase},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77487-z},
  url = {https://doi.org/10.1038/s41467-026-77487-z},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors in mice
AU  - Michael W. Gongwer
AU  - Fanny Etienne
AU  - Eric N. Moca
AU  - Sara V. Blagburn-Blanco
AU  - Megan S. Chappell
AU  - Keionna A. Newton
AU  - Daniel T. Gray
AU  - Jack P. Riley
AU  - Chloe R. Christensen
AU  - Russell N. Ahmed
AU  - Alexander S. Enos
AU  - Melody Haratian
AU  - Alex Qi
AU  - Rocio Rojo
AU  - Scott A. Wilke
AU  - Clare Pridans
AU  - Laura A. DeNardo
AU  - Lindsay M. De Biase
PY  - 2026
DA  - 2026/09/26
JO  - Nature Communications
DO  - 10.1038/s41467-026-77487-z
UR  - https://doi.org/10.1038/s41467-026-77487-z
AB  - While microglia are well known for pruning synapses during neurodevelopment, their role in synapse formation remains understudied. Here we investigate how microglial absence impacts synaptic development in the nucleus accumbens (NAc), a region critical for emotional regulation and motivated behaviors. Using genetically modified mice lacking microglia (Csf1rΔFIRE/ΔFIRE), we find blunted excitatory synapse formation in the NAc, particularly during the second and third postnatal weeks. Tissue-level NAc proteomics in the third postnatal week reveals changes in proteins involved in synapse structure, trans-synaptic signaling, and pre-synaptic function. Although electrophysiological changes largely resolve by adulthood, microglia-lacking mice exhibit persistent changes in threat avoidance behavior and underlying NAc neuronal activity. Transient depletion of NAc microglia during the second postnatal week similarly disrupts synapse formation and adult threat avoidance. Together, these findings identify a role for microglia in shaping NAc synaptic development and in establishing functional circuits that support adult behavioral function.
SN  - 2041-1723
ER  -