2. Academic Validation
  3. Impaired behavioral inhibition in Fmr1 KO mice is linked to disrupted visual cortex theta oscillations

Impaired behavioral inhibition in Fmr1 KO mice is linked to disrupted visual cortex theta oscillations

  • Cell Rep. 2026 Jun 20;45(7):117590. doi: 10.1016/j.celrep.2026.117590.
Michael P Zimmerman 1,  Mowen Yin 1,  Kevin R Cragg 1,  Sanghamitra Nareddula 2,  Varun M Kumar 3,  Violeta Saldarriaga 2,  Adriana Rotger 4,  Rachel Lehman 2,  Paige Edens 2,  Caroline Powell 2,  Jenna Barry 2,  Sein Kim 2,  Joseph G Makin 3,  Alexander A Chubykin 5
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA; Department of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
  • 2 Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA.
  • 3 Department of Electrical and Computer Engineering, Purdue University, West Lafayette, IN 47907, USA.
  • 4 Department of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
  • 5 Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN 47907, USA; Department of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: [email protected].
PMID: 42322609 DOI: 10.1016/j.celrep.2026.117590
Abstract

Fragile X syndrome (FX) is associated with sensory processing and learning deficits. Visual familiarity evokes persistent theta oscillations during passive stimulus presentation in the primary visual cortex (V1) and the hippocampus (HPC), which are impaired in V1 of FX. How does this activity change during active behavior? To address this, we performed Neuropixels recordings in V1, HPC, and the prefrontal cortex (PFC) during Go/No-Go visual discrimination behavior. Theta oscillations are reduced in FX in both V1 and HPC and are abolished during No-Go trials, correlating with excessive, incorrect licking behavior. In wild-type (WT) mice, V1 theta power strongly correlates with correct behavioral outcomes. PFC shows significantly reduced cue-related responses in FX. Together, these findings show loss of behavioral inhibition in FX correlated with attenuated theta activity in V1 and HPC and deficient top-down control from PFC. This work sheds light on circuit-level impairments underlying behavioral deficits in FX for potential therapeutic interventions.

Keywords

CP: neuroscience; autism; fragile X syndrome; hippocampus; learning; memory; neural circuits; prefrontal cortex; primary visual cortex; vision.

Figures
Products