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Genetic mapping identifies Homer1 as a developmental modifier of attention

Nature Neuroscience volume 29, pages 647–659 (2026)Cite this article

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Abstract

The genetic factors and resulting neural circuit physiology driving variation in attention are poorly understood. Here we took an unbiased forward genetics approach to identify genes of large effect on attention. We studied 200 genetically diverse mice and, through genetic mapping, identified a small locus on chromosome 13 (95% CI 92.22–94.09 Mb) that is significantly associated with variation in pre-attentive processing. Within the locus we identified a gene, Homer1, encoding a synaptic protein, whose downregulation during development led to improvements in multiple measures of attention in adulthood. Mechanistically, reduced Homer1 levels resulted in an upscaling of GABA receptors and enhanced inhibitory tone in the prefrontal cortex, leading to improved neural signal to noise and attentional performance. We thus identify a single genetic locus of large effect on attention and propose Homer1-dependent inhibitory tone, sculpted during a developmental sensitive period, as a key regulator and potential therapeutic target for attentional performance.

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Fig. 1: Identification of a QTL associated with pre-attentive processing.
Fig. 2: Chr13 QTL mediates variation in attentional performance.
Fig. 3: Chr13 QTL effects map to Homer1, but adult manipulations have no behavioral phenotype.
Fig. 4: Homer1a and Ania3 are developmental modifiers of attention.
Fig. 5: Low Homer1-expressing glutamatergic neurons upregulate GABA receptors.
Fig. 6: Developmental reduction of Homer1a/Ania3 alters prefrontal inhibitory influence, enhances SNR and improves attention.

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Acknowledgements

We thank the Rajasethupathy laboratory members for helpful discussions throughout. We thank J. Hudspeth for advice on testing auditory brainstem responses. We thank C. Bargmann, J. Friedman and R. Lifton for helpful discussions related to genetics and genetic mapping. We thank M. B. Hatten and B. Darnell for discussions related to developmental biology and Homer1 functions. We thank P. Greengard’s laboratory for sharing behavioral instrumentations and R. Sharma for suggestions on the scRNA-seq analysis. We thank J. Regalado for help with photometry experiments and analysis, J. Weisman for contributions to the dual-color photometry system, V. Li for stereotactic surgeries and J. Brandt and M. Kirylo for help with biochemistry experiments. We thank the core facilities at Rockefeller (Precision Instrumentation, Genomics, and FACS), the Memorial Sloan Kettering Cancer Center (Single Cell Analytics Innovation Laboratory) and the University of Arizona (Viral Production Core). Cartoons in some figures (Figs. 3, 4 and 6) were created with BioRender.com. This work was supported by a Kavli Institute pilot grant from The Rockefeller University (A.T.), a Medical Scientist Training Program grant from NIGMS (T32GM007739) to the Tri-Institutional MD-PhD Program (A.F.I.), and grants from the National Institutes of Health under award numbers F30HD100089 (A.F.I.), 2R01MH110553 (N.V.D.M.G.), DP2AG058487 (P.R.), as well as grants from the Pershing Foundation, Vallee Foundation and the Harold and Leila Mathers Foundation (P.R.).

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Authors and Affiliations

  1. Laboratory of Neural Dynamics & Cognition, The Rockefeller University, New York, NY, USA

    Zachary Gershon, Alessandra Bonito-Oliva, Andrea Terceros, Genelle Rankin, John Fak, Yujin Harada, Millennium Gebremedhin & Priya Rajasethupathy

  2. Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA

    Matt Kanke & Praveen Sethupathy

  3. Feil Family Brain and Mind Research Institute, Weill Cornell, New York, NY, USA

    Andrew F. Iannone & Natalia V. De Marco García

  4. Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY, USA

    Brian Fabella

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Contributions

Z.G., P.R. and P.S. conceived the study. Z.G., A.B.-O. and P.R. designed the experiments. Z.G. selected and optimized the behaviors, performed mouse behaviors (together with A.B.-O.), molecular studies including RNA preparation and single cell dissociation (together with A.T.), cloning and cell-based assays and in vivo neural activity recordings and analysis, supervised by P.R. M.K. performed QTL as well as RNA-seq analysis, supervised by P.S. A.T. assisted with designing and performing the scRNA-seq experiments and analysis. Z.G. and G.R. designed the head-fixed behaviors and G.R. performed these experiments. J.F., Y.H. and M.G. assisted with surgeries and histology. A.F.I. performed surgeries for the developmental study, supervised by N.V.D.M.G. B.F. performed auditory brainstem recordings. Z.G. and P.R. wrote the paper with input from all authors.

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Correspondence to Priya Rajasethupathy.

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Extended data

Extended Data Fig. 1 Additional genetic and behavioral characterization of DO mice.

Related to Fig. 1. a, Startle response assessed during PPI experiments in B6 (gray, n = 27) and DO (black, n = 176) mice measured as startle amplitude (V). Upper and lower box limits indicate 75th and 25th percentiles, centerline indicates the median, upper and lower whiskers are the maximum and minimum data points. b-d, Correlations in DO mice (n = 176) between (b) startle response, measured as the magnitude of startle amplitude (V), and PPI, measured as percent inhibition, at 3 (PP3, r2 = 0.005) and 12 (PP12, r2 = 0.014) dB above background, (c) weight and startle response (r2 = 1.084 ×10−5), and (d) weight and PPI (PP3, r2 = 0.003; PP6, r2 = 0.002; PP12, r2 = 0.008) dB above background. e, QTL mapping analysis (by R/qtl2), shown as Manhattan plots, of PPI at 3 (PPI3, red), 6 (PPI6, purple, genome-wide p < 0.01), and 12 dB (PPI12, magenta) above background (n = 176; blue lines indicate 90% confidence threshold and red lines indicate 95% confidence threshold).

Extended Data Fig. 2 Behavioral phenotype and covariate characterization of CC083 and CC025 mice.

Related to Fig. 2. a, Startle response, measured as the magnitude of the startle amplitude (V) in three CC lines with the Chr13 QTLWSB (low-performing) diplotype, CC025 (n = 7 M + 7 F), CC035 (n = 6 M + 3 F), and CC038 (n = 6 M + 6 F), and three CC lines with the Chr13 QTLB6 (high-performing) diplotype, CC002 (n = 6 M + 6 F), CC051 (n = 6 M + 6 F), and CC083 (n = 7 M + 7 F), two-sided Welch-corrected t-test between haplotypes p < 0.001. Upper and lower box limits indicate 75th and 25th percentiles, centerline indicates the median, upper and lower whiskers are the maximum and minimum data points. No significant interaction between sex and CC line by two-way ANOVA. b-d, Correlations in three CC lines with the Chr13 QTLWSB (low-performing) diplotype, CC025 (n = 7 M + 7 F), CC035 (n = 6 M + 3 F), and CC038 (n = 6 M + 6 F), and three CC lines with the Chr13 QTLB6 (high-performing) diplotype, CC002 (n = 6 M + 6 F), CC051 (n = 6 M + 6 F), and CC083 (n = 7 M + 7 F) between (b) startle response and PPI, measured as percent inhibition, at 3 dB (PP3), 6 dB (PP6), and 12 dB (PP12) above background, (c) weight and startle response, and (d) weight and PPI. e, Auditory brainstem response measured as minimum thresholds in CC025 (n = 3 M + 1 F) and CC083 (n = 2 M + 1 F) as sound pressure level (dB) in response to increasing frequencies (4, 8, 16, 32 kHz). f, Motor coordination measured in CC025 (n = 10 M + 12 F) and CC083 (n = 10 M + 12 F) as latency (s) to fall from the rod in the Rotarod test averaged across 4 consecutive trials. Significant difference between sexes but no significant interaction between sex and CC line by two-way ANOVA. g, Gross motor activity measured in CC025 (n = 11 M + 12 F) and CC083 (n = 11 M + 12 F) mice as total distance moved (inch) in a square open field arena during a 5-min test. Significant difference between sexes but no significant interaction between sex and CC line by two-way ANOVA. h-i, Performance of CC025 (n = 8 M + 10 F) and CC083 (n = 9 M + 12 F) mice during nosepoke shaping, where the motor activities required are the same as the SDT training but with no attentional component (that is cue), showing (h) the number of nosepokes per mouse on the day of nosepoke shaping when the mice met criteria to proceed to SDT training and (i) the average latency to nosepoke after retrieving a reward for each mouse that retrieved rewards on the first nosepoke shaping day. No significant interaction was found between sex and CC line by two-way ANOVA. j, Working memory performance assessed during a spontaneous alternation task in a Y-maze apparatus for CC025 (n = 9 M + 12 F) and CC083 (n = 13 M + 12 F) mice, measured as the percent of correct alternations (Methods). No significant interaction between sex and CC line by two-way ANOVA. k, Short-term memory tested by a novel object recognition test in CC025 (n = 9 M) and CC083 (n = 10 M) mice, measured as time spent exploring the novel object vs the familiar one and expressed as the percentage of total exploration time during a 5 min test. Two-way ANOVA showed a significant main effect for novelty (p < 0.0001), but not for CC line. l, Social behavior for CC025 (n = 9 M + 7 F) and CC083 (n = 8 M + 7 F) mice, expressed as discrimination index determined by exploration time in a 3-chamber social interaction test. Significant difference between sexes but no significant interaction between sex and CC line by two-way ANOVA. m, Anxiety-like behavior measured as time, in seconds, spent in the center of an open field arena during a 5 min test in CC025 (n = 8 M + 10 F) and CC083 (n = 11 M + 10 F). Significant main effects for CC line (p = 0.0007) and sexes (p = 0.0005) but no significant interaction between sex and CC line by two-way ANOVA. n, Anxiety-like behavior measured as the percentage of time spent in the open arm of an elevated plus maze during a 5-min test in CC025 (n = 9 M + 10 F) and CC083 (n = 11 M + 12 F) mice. Significant main effect for CC line (p = 0.0006) but no significant sex effect or interaction between sex and CC line by two-way ANOVA. Data in e-n are shown as mean ± SEM.

Extended Data Fig. 3 Further DO RNA-seq information, Homer1 exons, in vitro validation & additional behavioral characterization of Homer1 manipulations.

Related to Fig. 3. a, Heatmap of hierarchical clustering by Euclidean distance among gene expression profiles in DO high- (pink, n = 3) and low- performers (green, n = 3) as highlighted in Fig. 3a-b and from three brain regions per mouse: mediodorsal thalamus (MD, green), prefrontal cortex (PFC, orange) and ventral tegmental area (VTA, pink). Clustering is visible by brain region and performance in MD and PFC. b, Table showing protein-coding genes within the 95% CI surrounding the Chr13 QTL identified by rQTL2. c, Schematic representation of the Homer1 genomic exon structure. The bent arrow at the 5’ end of exon 1 (solid line, above) indicates the putative transcription start site, while the bent arrow at the 3’ end of exon 1 (dashed line, below) represents the translation start site. Black diamonds (below) indicate the translation stop sites of Homer1a, Ania3, and Homer1b/c, respectively. To create Homer1a, exon 5 extends into intron 5 to create the Homer1a-specific exon (5’) through alternative splicing. Ania3 is generated by alternative splice usage of intron 5 sequence downstream of exon 5’ as the Ania3-specific exon 6’. (Adapted from Bottai et al. 2002). Blue arrows indicate shRNA binding locations. d-e, in vitro validation of Homer1a gene knockdown construct. d, Representative images of HEK cells co-transfected with Homer1a (first and third images from the left) or Scramble (second and fourth images from the left) shRNA (red) and Homer1a (first and second images from the left) or Homer1b/c (third and fourth images from the left) expression constructs (green). Scale bar: 100 µm. e, Quantification of shRNA-mediated gene knockdown, expressed as the fraction of cells co-expressing a Homer1 isoform construct and shRNA construct relative to the total number cells expressing the shRNA construct, normalized to the respective scramble control experiments (two-way ANOVA showed significant main effects for Homer1 isoform expression, p < 0.0001, and shRNA construct, p < 0.0001, as well as a significant interaction between those variables, p < 0.0001; two-sided Holm–Sidak’s test for multiple comparisons showed a significant difference in Homer1a expression between the shRNA (purple, n = 10 fields of view across 2 independent experiments) and Scramble (blue, n = 8 fields of view across 2 independent experiments) constructs, p < 0.0001). f, Startle response in Homer1a KD (n = 14) and Scramble (n = 14) mice. g, Electropherogram of AAV-CaMKII(1.3)-Homer1a-eYFP overexpression construct aligned to the Homer1a coding sequence (tan bar near the top of each line). The height of gray boxes at the top of each line is proportional to the number of sequencing runs aligned to the reference sequence (maximum # of sequencing runs in image = 2). h, Startle response in Homer1a OE (n = 9) and control eYFP (n = 10) mice. i, Representative images of HEK cells co-transfected with Ania3 (first and third images from the left) or Scramble (second and fourth images from the left) shRNA (red) and Ania3 (first and second images from the left) or Homer1b/c (third and fourth images from the left) expression constructs (green), Scale bar: 100 µm. j, Quantification of shRNA-mediated gene knockdown, expressed as the fraction of cells co-expressing the Ania3 expression construct and shRNA or scramble construct relative to the total number cells expressing the shRNA or scramble, normalized to the scramble control experiments. In cells transfected with the Ania3 expression construct, there was a significant difference in Ania3 expression between the cells co-transfected with the shRNA (n = 5 fields of view), and Scramble (n = 5 fields of view) constructs (unpaired two-sided t-test, p < 0.0001). k, Schematic of constructs and injection location (PFC) for knockdown (KD, purple) and control (Scramble, blue) in adult B6 mice. l, Validation histology performed 12 weeks after bilateral injection of pooled AAV-U6-Homer1a_shRNA-EF1a-mCherry and AAV-U6-Ania3_shRNA-EF1a-mCherry viruses for KD (purple, upper panel) and AAV-U6-Scramble-EF1A-mCherry control virus for Scramble (blue, lower panel) into PFC, showing viral transduction in the target area (DAPI, blue; mCherry, red). Scale bars: 1000 µm. m-n, PPI (m) and startle response (n) in Scramble (n = 10) and adult Homer1a/Ania3 KD (n = 9) mice. Data in e, j, and m are expressed as mean ± SEM, and for f, h, and n, upper and lower box limits indicate 75th and 25th percentiles, centerline indicates the median, upper and lower whiskers are the maximum and minimum data points.

Extended Data Fig. 4 In vitro characterization of Ania3 shRNA construct and in vivo characterization of developmental knockdown (KDdev) manipulation.

Related to Fig. 4. a, Representative histology by in situ RNA hybridization of unilateral developmental knockdown injection at p15. Image is representative of 3 independent samples. Left: 4x merged image showing Homer1a and shRNA expression, scale bar: 1000 µm. White box indicates the region used for higher magnification images. Center: 20x image of Homer1a expression only (left), mCherry expression only (center), and both Homer1a and mCherry expression (right), scale bars: 100 µm. For all images, Homer1a is shown in green and mCherry is shown in red. b, ex vivo validation of developmental knockdown manipulation assessed by quantification of Homer1a (left), Ania3 (center) and Homer1b/c (right) levels measured by qPCR in PFC samples dissected from Scramble (n = 12) and KDdev (n = 15), (two-way ANOVA showed significant main effects for group, p < 0.0001, and Homer1 isoform expression, p < 0.0001; post hoc Holm–Sidak’s test for multiple comparisons shows a significant difference in Homer1a, p = 0.0038, and Ania3, p = 0.0451, expression). c, Western blot for Homer1b/c in Scramble and KDdev mice (n = 4 per group) 4 months after injection. Raw western blot images can be found in Supplementary Fig. 1. d, Startle response in Scramble (n = 12 M + 8 F) and KDdev, (n = 10 M + 8 F). e-g, Correlations between (e) startle response and PPI, measured as percent inhibition, at 3 dB (PP3), 6 dB (PP6), and 12 dB (PP12) above background, (f) weight (g) and startle response, and (g) weight and PPI. h-i, Performance during nosepoke shaping, where the motor activities required are the same as the SDT training but with no attentional component (that is cue) for scramble (n = 12 M + 7 F) and KDdev (n = 12 M + 8 F) mice, showing (h) the number of nosepokes per mouse on the day of nosepoke shaping when the mice met criteria to proceed to SDT training and (i) the average latency to nosepoke after retrieving a reward for each mouse that retrieved rewards on the first nosepoke shaping day. No significant interaction between sex and group by two-way ANOVA.j, Auditory brainstem response measured as minimum thresholds in Scramble (n = 4 M + 1 F) and KDdev (n = 4 M + 1 female), as sound pressure level (dB) in response to increasing frequencies (4, 8, 16, 32 kHz). k, Motor coordination in the Rotarod test for Scramble (n = 13 M + 8 F) and KDdev (n = 12 M + 8 F), measured as latency (s) to fall from the rod averaged across 4 consecutive trials. Significant difference between sexes but no significant interaction between sex and group by two-way ANOVA. l, Gross motor activity measured as distance moved (inch) by Scramble (n = 13 M + 8 F) and KDdev (n = 12 M + 8 F) in a square open field arena during a 5-min test. m, Schematic of head-fixed SDT setup (left) and task structure (right). n, Quantification of the latency to first lick (sec) within the decision windows across cue lengths. Each point is the average latency to first lick for the first 3 Go trials per animal (2 s cue: Scramble n = 7 M, KDdev n = 8 M; 1 s and 0.5 s cues: Scramble n = 8 M, KDdev n = 7 M). o, Quantification of the latency to first lick jitter across cue lengths. Jitter is quantified as the standard deviation of first lick latencies across the first 3 Go trials (two-way ANOVA showed a significant main effect for group, p = 0.007, and post hoc Holm–Sidak’s test for multiple comparisons showed significant differences between groups at 1 and 0.5 s cues, p = 0.04 for both cue lengths, 2 s cue: Scramble n = 7 M, KDdev n = 8 M; 1 s and 0.5 s cues: Scramble n = 8 M, KDdev n = 7 M). p, Schematic of the Attentional Set Shift setup and experiment protocol. q, Latency (s) to retrieve the chocolate pellet measured in Scramble (n = 14 M) and KDdev, (n = 13 M) mice during the 4 trials of the Attentional Set Shift test. Significant interaction between trial and group, p = 0.04, by repeated-measures two-way ANOVA. r, Working memory performance assessed in a Y-maze apparatus for Scramble (n = 12 M + 7 F) and KDdev, (n = 13 M + 8 F) mice, measured as correct alternations performed, expressed as a percentage total alternations. Significant difference between sexes but no significant interaction between sex and group by two-way ANOVA. s, Short-term memory tested by a novel object recognition test in Scramble (n = 7 M) and KDdev, (n = 7 M) mice, measured as time spent exploring the novel object vs the familiar one and expressed as a percentage of total exploration time during a 5 min test. significant main effect for novelty (p < 0.001), but not for group by two-way ANOVA. t-u, Anxiety-like behavior measured as (t) time (in seconds) spent in the center of an open field arena during a 5 min test in Scramble (n = 13 M + 8 F) and KDdev, (n = 12 M + 8 F) mice, and (u) percentage of time spent in the open arm of an elevated plus maze during a 5 min test in Scramble (n = 12 M + 8 F) and KDdev, (n = 13 M + 8 F) mice. Significant difference between sexes but no significant interaction between sex and group by two-way ANOVA for both t and u. Data in h-l, n-o, and q-u are expressed as mean ± SEM, and for b and d, upper and lower box limits indicate 75th and 25th percentiles, centerline indicates the median, upper and lower whiskers are the maximum and minimum data points.

Extended Data Fig. 5 Additional information for scRNA-seq experiments.

Related to Fig. 5. a, Violin Plots of library size for each biological replicate (0=pooled CC025 sample 1, 1=pooled CC083 sample 1, 2=pooled CC025 sample 2, 3=pooled CC083 sample 2). Box-and-whiskers depict the median and interquartile range, lower bound = 25th percentile, center = median, upper bound = 75th percentile, lower whisker = smallest data point ≥ (Q1 - 1.5 x IQR), upper whisker = largest data point ≤ (Q3 + 1.5 x IQR). b, UMAP visualization of initial clusters colored by line. c, Heatmap of select cell type marker genes for clusters shown in b. d, Identification of the cortical layers neuron clusters likely belong to based on the expression of canonical marker genes (Methods) e-f, Dot plots showing scaled expression of select GABAergic receptors driving GO analysis of genes upregulated in the CC083 glutamatergic Homer1 differentially expressed (DE) clusters (Fig. 5h) in both the glutamatergic (e) DE and (f) non-differentially expressed clusters stratified by cluster, line, and Homer1 positivity. g, Gene ontology (GO) analysis of molecular function by Enrichr for genes upregulated in CC025 cells within the glutamatergic Homer1 differentially expressed (DE) clusters. h, Functional pathway enrichment analysis for CC083 cells in the GABAergic cluster using the Elsiver_Pathway_Collection gene set library in Enrichr. i, Dot plot showing the expression of markers for common neuromodulatory systems in GABAergic cluster 7 by line. j, Dot plot of adrenergic receptors and transporters in CC025 and CC083 cells in GABAergic neurons (cluster 7, Fig. 5c). k, UMAP visualization sub-clustering all cells identified as GABAergic neurons (cluster 7, Fig. 5c) labeled by most strongly expressed interneuron subtype marker and most highly expressed gene. l, UMAP visualization of scaled ADRA1B expression in GABAergic neuronal clusters. m, UMAP visualization of all cells collected from KDdev and scramble mice (n = 3 mice pooled per group) clustered based on transcriptional profile. n, UMAP visualization sub-clustering all cells identified as neurons, identified as excitatory (glutamatergic) and inhibitory (GABAergic) neuron clusters based on expression of canonical marker genes. o, Differential Homer1 expression between Scramble and KDdev neurons by cluster (two-sided unpaired t-tests, glutamatergic cluster p = 0.0243 and GABAergic cluster p = 0.0249). Data shown as mean ± SD. p, Correlation of the normalized expression differences of GABA receptor subunit and related adaptor gene set between the CC083/CC025 and KDdev/Scramble (r2 = 0.3653, p = 0.017, two-sided Pearson’s correlation). Genes expressed in less fewer than 20 cells in any of the groups were excluded from the analysis. For e-f and i-j, the size of each dot corresponds to the percentage of cells from each group expressing each gene or gene set, and the color intensity indicates the relative, scaled expression of the gene/gene set. For g-h raw P-values determined using a one-sided Fisher’s exact test.

Extended Data Fig. 6 Homer1 isoform expression, SDT behavioral performance, and additional photometry data.

Related to Fig. 6. a, PFC expression of Homer1a and Homer1b/c by qPCR in B6, CC025, and CC083 adult mice (Homer1a: nB6 = 5, nCC025 = 4, and nCC083 = 5; Homer1b/c: n = 5 per line; two-way ANOVA showed significant main effects for strain, Homer1 isoform, and a significant interaction between those variables, p < 0.0001 for all; post hoc Holm–Sidak’s test showed significant differences for B6 vs CC083 and CC025 vs CC083, p < 0.0001 for both). b, Performance of B6 (n = 5) and CC083 (n = 4) mice during SDT across days showing the percentage of correct responses (two-way ANOVA, p = 0.0024). Tethering mice to fibers impacted performance for both lines equally. c, Pairwise Pearson’s correlations between LC and PFC neuronal activity at baseline (two-sided Welch-corrected t-test for B6 vs CC083, n = 4 each, 5 min recordings, p < 0.0001). d, Top: representative traces from PFC (top) and LC neurons (bottom) from day 3 (left) and 11 (right), Y-axis is z-scored df/f and X-axis is time (s). Brown rectangles indicate cues. Bottom: Pairwise Pearson’s correlations between LC and PFC activity during SDT sessions in B6 (n = 5) and CC083 (n = 4) mice. Each 20 min session was split into 5, 4-min blocks. Data is shown from the first 4-minute block (left) and for blocks 2–5 (right) as mean ± SEM (two-sided Welch-corrected t-tests for days 1–3 vs days 9-11 within strain, for CC083 p(block1)=0.003 and p(blocks 2–5) < 0.0001). e, Representative DAPI-stained (blue) histology image of dual-color photometry surgical preparation to simultaneously record from excitatory and inhibitory neurons in PFC by injecting AAV-mDlx-GCaMP6f (green) contralateral to AAV-CaMKII-Cre + AAV-CAG-FLEX-jRGECO1a (red) and implanting fibers above the injection site (indicated by white dashed outlines). Image is representative of 3 independent samples. Scale bar: 1000 µm. f, Accuracy (percentage of correct responses) for Scramble (n = 6) and KDdev mice (n = 10). Two-way ANOVA showed a significant interaction between training session and group (p = 0.002). g, Average activity (area under responses) in home cage for Scramble (n = 6) vs KDdev (n = 10) during 1 min recordings from PFC excitatory neurons. h, Robust trial-averaged responses from 5 seconds before to 5 seconds after cue onset for correct 5 s cue trials - 810 trials for Scramble (gray, n = 6 mice) and 1,641 trials for KDdev (purple, n = 10 mice). Data are mean (dark line) and SEM (shaded area). Photometry scale: x/y: 1 s/0.1z. i, PFC inhibitory activity in task during the last 5 seconds of ITIs for trials on all days in Scramble (n = 6) and KDdev (n = 10) mice (two-sided unpaired t-test, p = 0.001). j, Robust trial-averaged responses from 2 seconds before to 10 seconds after ITI onset after 5 s cue trials - 805 ITIs for Scramble (gray, n = 6 mice) and 1,634 ITIs for KDdev (purple, n = 10 mice). Data are mean (dark line) and SEM (shaded area). Photometry scale: x/y: 1 s/0.05z. Data in a-d, f-g, and i are expressed as mean ± SEM.

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Gershon, Z., Bonito-Oliva, A., Kanke, M. et al. Genetic mapping identifies Homer1 as a developmental modifier of attention. Nat Neurosci 29, 647–659 (2026). https://doi.org/10.1038/s41593-025-02155-2

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