Sex difference in cue strategy in a modified version of the Morris water task: correlations between brain and behaviour.

BACKGROUND: Sex differences in spatial memory function have been reported with mixed results in the literature, with some studies showing male advantages and others showing no differences. When considering estrus cycle in females, results are mixed at to whether high or low circulating estradiol results in an advantage in spatial navigation tasks. Research involving humans and rodents has demonstrated males preferentially employ Euclidean strategies and utilize geometric cues in order to spatially navigate, whereas females employ landmark strategies and cues in order to spatially navigate. METHODOLOGY/PRINCIPAL FINDINGS: This study used the water-based snowcone maze in order to assess male and female preference for landmark or geometric cues, with specific emphasis placed on the effects of estrus cycle phase for female rat. Performance and preference for the geometric cue was examined in relation to total hippocampal and hippocampal subregions (CA1&2, CA3 and dentate gyrus) volumes and entorhinal cortex thickness in order to determine the relation between strategy and spatial performance and brain area size. The study revealed that males outperformed females overall during training trials, relied on the geometric cue when the platform was moved and showed significant correlations between entorhinal cortex thickness and spatial memory performance. No gross differences in behavioural performance was observed within females when accounting for cyclicity, and only total hippocampal volume was correlated with performance during the learning trials. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the sex-specific use of cues and brain areas in a spatial learning task

Maximum entorhinal cortex thickness (mm).

<p>Maximum entorhinal cortex thickness (mm).</p

Heading error.

<p>The number represents the percentage per group that had an initial heading error that indicated initial orientation to the geometric cue (N per group).</p

Correlations.

*<p>indicates p<.05, bold indicates that the measure accounts for more than 10% of the variance.</p>a<p>Spearmans r, with dichotomized variable.</p

Snowcone maze behaviour.

<p>A. Latency to reach platform on day 3 and 4 for males and females. Inset: latency to reach platform on trial 1 for Day 3 and 4. B. Heading error on Day 4 trial 1 for males and females. C. Dwell time in the geometric cue quadrant for males and females. Note the geometric quadrant would be considered the NE quadrant from Fig. 1A. *indicates p<0.05, **indicates p<0.01.</p

Correlations between behaviour and volume/thickness measurements in male rats.

*<p>indicates p<.05, bold indicates that the measure accounts for more than 10% of the variance.</p>a<p>Spearmans r, with dichotomized variable.</p>**<p>n.a. as all rats headed to the geometric cue.</p

Correlations between behaviour and volume/thickness measurements in female rats.

*<p>indicates p<.05, bold indicates that the measure accounts for more than 10% of the variance.</p>a<p>Spearmans r, with dichotomized variable.</p><p><b><i>Abbreviations:</i></b></p><p>CA1–Cornu Ammonis area 1 (hippocampal subregion).</p><p>CA2–Cornu Ammonis area 2 (hippocampal subregion).</p><p>CA3–Cornu Ammonis area 3 (hippocampal subregion).</p><p>DG–dentate gyrus.</p><p>EC–entorhinal cortex; note AV EC, LT EC and RT EC correspond to average, left and right entorhinal cortex respectively.</p><p>HP–hippocampus.</p

Description of snowcone maze.

<p>A. Overheard view of snow cone maze. NE, NW, SW, SE indicate starting positions used on all training days. B. Day 1–3. C. Day 4. Black square indicates platform position. X indicates landmark cue (balloon).</p

Hnrnpul1 controls transcription, splicing, and modulates skeletal and limb development in vivo

Mutations in RNA-binding proteins can lead to pleiotropic phenotypes including craniofacial, skeletal, limb, and neurological symptoms. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in nucleic acid binding, transcription, and splicing through direct binding to DNA and RNA, or through interaction with other proteins in the spliceosome. We show a developmental role for Hnrnpul1 in zebrafish, resulting in reduced body and fin growth and missing bones. Defects in craniofacial tendon growth and adult-onset caudal scoliosis are also seen. We demonstrate a role for Hnrnpul1 in alternative splicing and transcriptional regulation using RNA-sequencing, particularly of genes involved in translation, ubiquitination, and DNA damage. Given its cross-species conservation and role in splicing, it would not be surprising if it had a role in human development. Whole-exome sequencing detected a homozygous frameshift variant in HNRNPUL1 in 2 siblings with congenital limb malformations, which is a candidate gene for their limb malformations. Zebrafish Hnrnpul1 mutants suggest an important developmental role of hnRNPUL1 and provide motivation for exploring the potential conservation of ancient regulatory circuits involving hnRNPUL1 in human development.We thank the Alberta Children’s Hospital Research Institute for funding for DB and SF through the MORPH project. Operating funding was received from the Canadian Institute of Health Research Institute of Genetics Rare Disease Models and Mechanisms (180309-001-001) and from the National Science and Engineering Research Council (RGPIN/07176-2019) to SJ