Coherent representations of subjective spatial position in primary visual cortex and hippocampus, bioRxiv, 2017-12-19

A major role of vision is to guide navigation, and navigation is strongly driven by vision1-4. Indeed, the brain’s visual and navigational systems are known to interact5, 6, and signals related to position in the environment have been suggested to appear as early as in visual cortex6, 7. To establish the nature of these signals we recorded in primary visual cortex (V1) and in the CA1 region of the hippocampus while mice traversed a corridor in virtual reality. The corridor contained identical visual landmarks in two positions, so that a purely visual neuron would respond similarly in those positions. Most V1 neurons, however, responded solely or more strongly to the landmarks in one position. This modulation of visual responses by spatial location was not explained by factors such as running speed. To assess whether the modulation is related to navigational signals and to the animal’s subjective estimate of position, we trained the mice to lick for a water reward upon reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1 encoded the animal’s position along the corridor, and the errors in their representations were correlated. Moreover, both representations reflected the animal’s subjective estimate of position, inferred from the animal’s licks, better than its actual position. Indeed, when animals licked in a given location – whether correct or incorrect – neural populations in both V1 and CA1 placed the animal in the reward zone. We conclude that visual responses in V1 are tightly controlled by navigational signals, which are coherent with those encoded in hippocampus, and reflect the animal’s subjective position in the environment. The presence of such navigational signals as early as in a primary sensory area suggests that these signals permeate sensory processing in the cortex.

biorxiv neuroscience 100-200-users 2017

Long-read sequencing of nascent RNA reveals coupling among RNA processing events, bioRxiv, 2017-12-19

AbstractPre-mRNA splicing is accomplished by the spliceosome, a megadalton complex that assembles de novo on each intron. Because spliceosome assembly and catalysis occur co-transcriptionally, we hypothesized that introns are removed in the order of their transcription in genomes dominated by constitutive splicing. Remarkably little is known about splicing order and the regulatory potential of nascent transcript remodeling by splicing, due to the limitations of existing methods that focus on analysis of mature splicing products (mRNAs) rather than substrates and intermediates. Here, we overcome this obstacle through long-read RNA sequencing of nascent, multi-intron transcripts in the fission yeast Schizosaccharomyces pombe. Most multi-intron transcripts were fully spliced, consistent with rapid co-transcriptional splicing. However, an unexpectedly high proportion of transcripts were either fully spliced or fully unspliced, suggesting that splicing of any given intron is dependent on the splicing status of other introns in the transcript. Supporting this, mild inhibition of splicing by a temperature-sensitive mutation in Prp2, the homolog of vertebrate U2AF65, increased the frequency of fully unspliced transcripts. Importantly, fully unspliced transcripts displayed transcriptional read-through at the polyA site and were degraded co-transcriptionally by the nuclear exosome. Finally, we show that cellular mRNA levels were reduced in genes with a high number of unspliced nascent transcripts during caffeine treatment, showing regulatory significance of co-transcriptional splicing. Therefore, overall splicing of individual nascent transcripts, 3’ end formation, and mRNA half-life depend on the splicing status of neighboring introns, suggesting crosstalk among spliceosomes and the polyA cleavage machinery during transcription elongation.

biorxiv molecular-biology 0-100-users 2017

 

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