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Griffiths, A. M.

Publications and source records attributed to Griffiths, A. M..

2 recordsLinked to original sources

Interdependence of primary and secondary somatosensory cortices for plasticity and texture discrimination learning

Feedforward and feedback pathways are important for transfer and integration of information between sensory cortical areas. Here we find that two closely connected cortical areas, the primary (S1) and secondary somatosensory cortices (S2) are both required for mice to learn a whisker-dependent texture discrimination. Increased inhibition in either area (using excitatory DREADDs expressed in inhibitory interneurones) prevents learning. We find that learning the discrimination produces structural plasticity of dendritic spines on layer 2/3 pyramidal neurones in vibrissae S1 that is restricted to the basal dendrites and leaves dendritic spines on apical dendrites unchanged. As S2 projects to the apical dendrites of S1 neurones, we tested whether S2 affects LTP-induction in S1. We found that feedback projections from S2 to S1 gates LTP on feedforward pathways within S1. These studies therefore demonstrate the interdependence of S1 and S2 for learning and plasticity in S1. HIGHLIGHTSO_LIBoth primary (S1) and secondary (S2) somatosensory cortices are necessary for whisker based texture discrimination learning C_LIO_LIS2 feedback connections to S1 gate LTP at feedforward pathways in S1 C_LIO_LIS1 undergoes structural plasticity of pre-existing spines during learning C_LIO_LIS1 learning induced plasticity and LTP occurs on basal but not apical dendrites C_LI

neuroscience↗

Stratification of Risk of Progression to Colectomy in Ulcerative Colitis using Measured and Predicted Gene Expression

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of ulcerative colitis (UC) patients require colectomy within five years of diagnosis, but polygenic risk scores (PRS) utilizing findings from GWAS are unable to provide meaningful prediction of this adverse status. By contrast, in Crohns disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a Transcriptional Risk Score (TRS). Here we demonstrate that both measured (TRS) and polygenic predicted gene expression (PPTRS) identify UC patients at 5-fold elevated risk of colectomy with data from the PROTECT clinical trial and UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with transcriptome-wide association studies to stratify risk of disease complications.

genetics↗