Attention depends on the brain’s ability to suppress background activity while responding to relevant cues. A study in Nature Neuroscience reports that lowering the activity of specific isoforms of the gene Homer1 improves attentional performance in mice by reducing baseline neural noise in the prefrontal cortex.
The work points to an unexpected mechanism. Instead of amplifying activity in attention circuits, as stimulant medications do, the researchers found that dampening background signaling can sharpen focus. “The gene we found has a striking effect on attention and is relevant to humans,” said Priya Rajasethupathy, who led the study at Rockefeller University.
To identify genetic contributors to attention, the team analyzed nearly 200 genetically diverse mice derived from eight parental lines. This design captured variation closer to that seen in human populations. High-performing mice consistently showed lower expression of Homer1 in the prefrontal cortex. The locus containing Homer1 explained close to 20 percent of the variation in attention across animals. “Even accounting for any overestimation here of the size of this effect, which can happy for many reasons, that’s a remarkable number,” Rajasethupathy said.
Further experiments narrowed the effect to two activity-dependent isoforms, Homer1a and Ania3. Reducing these isoforms during adolescence, but not adulthood, led to faster and more accurate performance across attention tasks, with fewer distractions.
Mechanistic analyses showed that lowering Homer1 increased expression of GABA receptors in prefrontal neurons. This shift reduced baseline firing while preserving strong responses to task-relevant cues. “We were sure that the more attentive mice would have more activity in the prefrontal cortex, not less,” Rajasethupathy said. “But it made some sense. Attention is, in part, about blocking everything else out.”
The findings align with genetic links between Homer1 and neurodevelopmental conditions that feature early sensory disruptions, including ADHD, autism, and schizophrenia. The authors note that Homer1 contains a splice site that could be pharmacologically targeted. “There is a splice site in Homer1 that can be pharmacologically targeted,” Rajasethupathy said, “which may be an ideal way to help dial the knob on brain signal-to-noise levels.”
Publication Details
Gershon, Z., Bonito-Oliva, A., Kanke, M. et al. Genetic mapping identifies Homer1 as a developmental modifier of attention. Nat Neurosci (2025). https://doi.org/10.1038/s41593-025-02155-2
The work points to an unexpected mechanism. Instead of amplifying activity in attention circuits, as stimulant medications do, the researchers found that dampening background signaling can sharpen focus. “The gene we found has a striking effect on attention and is relevant to humans,” said Priya Rajasethupathy, who led the study at Rockefeller University.
To identify genetic contributors to attention, the team analyzed nearly 200 genetically diverse mice derived from eight parental lines. This design captured variation closer to that seen in human populations. High-performing mice consistently showed lower expression of Homer1 in the prefrontal cortex. The locus containing Homer1 explained close to 20 percent of the variation in attention across animals. “Even accounting for any overestimation here of the size of this effect, which can happy for many reasons, that’s a remarkable number,” Rajasethupathy said.
Further experiments narrowed the effect to two activity-dependent isoforms, Homer1a and Ania3. Reducing these isoforms during adolescence, but not adulthood, led to faster and more accurate performance across attention tasks, with fewer distractions.
Mechanistic analyses showed that lowering Homer1 increased expression of GABA receptors in prefrontal neurons. This shift reduced baseline firing while preserving strong responses to task-relevant cues. “We were sure that the more attentive mice would have more activity in the prefrontal cortex, not less,” Rajasethupathy said. “But it made some sense. Attention is, in part, about blocking everything else out.”
The findings align with genetic links between Homer1 and neurodevelopmental conditions that feature early sensory disruptions, including ADHD, autism, and schizophrenia. The authors note that Homer1 contains a splice site that could be pharmacologically targeted. “There is a splice site in Homer1 that can be pharmacologically targeted,” Rajasethupathy said, “which may be an ideal way to help dial the knob on brain signal-to-noise levels.”
Publication Details
Gershon, Z., Bonito-Oliva, A., Kanke, M. et al. Genetic mapping identifies Homer1 as a developmental modifier of attention. Nat Neurosci (2025). https://doi.org/10.1038/s41593-025-02155-2