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Morris, R.

Publications and source records attributed to Morris, R..

4 recordsLinked to original sources

Integrated accounts of behavioral and neuroimaging data using flexible recurrent neural network models

Neuroscience studies of human decision-making abilities commonly involve sub-jects completing a decision-making task while BOLD signals are recorded using fMRI. Hypotheses are tested about which brain regions mediate the effect of past experience, such as rewards, on future actions. One standard approach to this is model-based fMRI data analysis, in which a model is fitted to the behavioral data, i.e., a subjects choices, and then the neural data are parsed to find brain regions whose BOLD signals are related to the models internal signals. However, the internal mechanics of such purely behavioral models are not constrained by the neural data, and therefore might miss or mischaracterize aspects of the brain. To address this limitation, we introduce a new method using recurrent neural network models that are flexible enough to be jointly fitted to the behavioral and neural data. We trained a model so that its internal states were suitably related to neural activity during the task, while at the same time its output predicted the next action a subject would execute. We then used the fitted model to create a novel visualization of the relationship between the activity in brain regions at different times following a reward and the choices the subject subsequently made. Finally, we validated our method using a previously published dataset. We found that the model was able to recover the underlying neural substrates that were discovered by explicit model engineering in the previous work, and also derived new results regarding the temporal pattern of brain activity.

neuroscience

Transcriptional variation and divergence of host-finding behaviour in Steinernema carpocapsae infective juveniles

Steinernema carpocapsae is an entomopathogenic nematode that employs nictation and jumping behaviours to find host insects. We aimed to investigate the transcriptional basis of variant host-finding behaviours in the infective juvenile (IJ) stage of three S. carpocapsae strains (ALL, Breton and UK1). RNA-seq analysis revealed that whilst up to 28% of the S. carpocapsae transcriptome was differentially expressed (P<0.0001) between strains, remarkably few of the most highly differentially expressed genes (>2 log2 fold change, P<0.0001) were from neuronal gene families. S. carpocapsae Breton displays increased chemotaxis toward the laboratory host Galleria mellonella, relative to the other strains. This correlates with the up-regulation of four srsx chemosensory GPCR genes, and a sodium transporter gene, asic-2, relative to both ALL and UK1 strains. The UK1 strain exhibits a decreased nictation phenotype relative to ALL and Breton strains, which correlates with co-ordinate up-regulation of neuropeptide like protein 36 (nlp-36), and down-regulation of an srt family GPCR gene, and a distinct asic-2-like sodium channel paralogue. To further investigate the link between transcriptional regulation and behavioural variation, we sequenced microRNAs across IJs of each strain. We have identified 283 high confidence microRNA genes, yielding 321 isomiR variants in S. carpocapsae, and find that up to 36% of microRNAs are differentially expressed (P<0.0001) between strains. Many of the most highly differentially expressed microRNAs (>2 log2 fold, P<0.0001) are predicted to regulate a variety of neuronal genes that may contribute to variant host-finding behaviours. We have also found evidence for differential gene isoform usage between strains, which alters predicted microRNA interactions, and could contribute to the diversification of behaviour. These data provide deeper insight to the transcriptional landscape of behavioural variation in S. carpocapsae, underpinning efforts to functionally dissect the parasite host-finding apparatus.\n\nAuthor summarySteinernema carpocapsae is a lethal parasite of insects. In order to find and invade a host insect, the S. carpocapsae infective juvenile will typically stand upright, waving its anterior in the air as it searches for host-specific cues. When the infective juvenile senses insect volatile compounds and movement (both signals are required), it will attempt to jump towards the source of those stimuli. Whilst the jumping behaviour is unique to Steinernema species nematodes, nictation is a host-finding behaviour shared with other important parasites of medical and veterinary importance. We have found that different strains of S. carpocpsae use modified host-finding strategies, and that these behavioural differences correlate with gene expression patterns, identifying genes that may be crucial in regulating aspects of host-finding. We also assessed the complement of microRNAs, which are small non-coding RNAs that regulate target gene expression. We found a surprising difference in the abundance of shared microRNAs between strains of S. carpocapsae; these differences also reveal expression differences that correlate with behavioural variation. Predicted microRNA target genes suggest that microRNA variation could significantly influence the behaviour of nematodes. Broadly, this study provides insight to the relationship between gene expression and behaviour, paving the way for detailed studies on gene function.

animal behavior and cognition

Formation of functional, non-amyloidogenic fibres by recombinant Bacillus subtilis TasA

Bacterial biofilms are communities of microbial cells encased within a self-produced polymeric matrix. In the Bacillus subtilis biofilm matrix the extracellular fibres of TasA are essential. Here a recombinant expression system allows interrogation of TasA, revealing that monomeric and fibre forms of TasA have identical secondary structure, suggesting that fibrous TasA is a linear assembly of globular units. Recombinant TasA fibres form spontaneously, and share the biological activity of TasA fibres extracted from B. subtilis, whereas a TasA variant restricted to a monomeric form is inactive and subjected to extracellular proteolysis. The biophysical properties of both native and recombinant TasA fibres indicate that they are not functional amyloid-like fibres. A gel formed by TasA fibres can recover after physical shear force, suggesting that the biofilm matrix is not static and that these properties may enable B. subtilis to remodel its local environment in response to external cues. Using recombinant fibres formed by TasA orthologues we uncover species variability in the ability of heterologous fibres to cross-complement the B. subtilis tasA deletion. These findings are indicative of specificity in the biophysical requirements of the TasA fibres across different species and/or reflect the precise molecular interactions needed for biofilm matrix assembly.\n\nContributionsConceived and designed the experiments: CE, EE, RG, CEM, RJM, MS, NSW; Performed the experiments: KB, LC, CE, EE, PKF, RG, CEM, RJM, MS, TS; Contributed new analytical tools: CE, EE, RG, TS; Analysed the data: CE, EE, CEM, RJM, MS, LCS, NSW; Wrote the paper: EE, RJM, CEM, MS, NSW.

microbiology

Regulatory divergence of flowering time genes in the allopolyploid Brassica napus

Polyploidy is a recurrent feature of eukaryotic evolution and has been linked to increases in complexity, adaptive radiation and speciation. Within angiosperms, such events occur repeatedly in many plant lineages. We investigated the role of duplicated genes in the regulation of flowering in Brassica napus. This relatively young allotetraploid represents a snapshot of evolution and artificial selection in progress. In line with the gene balance hypothesis, we find preferential retention of expressed flowering time genes relative to the whole genome. Furthermore, gene expression dynamics across development reveal diverged regulation of many flowering time gene copies. This finding supports the concept of responsive backup circuits being key for the retention of duplicated genes. A case study of BnaTFL1 reveals differences in cis-regulatory elements downstream of these genes that could explain this divergence. Such differences in the regulatory dynamics of duplicated genes highlight the challenges for translating gene networks from model to more complex polyploid crop species.

plant biology