Biology subjects

Verpeut, J. L.

Publications and source records attributed to Verpeut, J. L..

2 recordsLinked to original sources

bioRxiv2020

Parallel organization of cerebellar pathways to sensorimotor, associative, and modulatory forebrain

Cerebellar outputs take polysynaptic routes to reach the rest of the brain, impeding conventional tracing. Here we quantify pathways between cerebellum and forebrain using transsynaptic tracing viruses and a whole-brain quantitative analysis pipeline. Retrograde tracing found a majority of descending paths originating from somatomotor cortex. Anterograde tracing of ascending paths encompassed most thalamic nuclei, especially ventral posteromedial, lateral posterior, mediodorsal, and reticular nuclei; in neocortex, sensorimotor regions contained the most labeled neurons, but higher densities were found in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Patterns of ascending expression correlated with c-Fos expression after optogenetic inhibition of Purkinje cells. Our results reveal homologous networks linking single areas of cerebellar cortex to diverse forebrain targets. We conclude that shared areas of cerebellum are positioned to provide sensory-motor information to regions implicated in both movement and nonmotor function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/979153v3_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1bead0corg.highwire.dtl.DTLVardef@1531de2org.highwire.dtl.DTLVardef@1cf02f6org.highwire.dtl.DTLVardef@1cb6774_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

SMALL ALPHAHERPESVIRUS LATENCY-ASSOCIATED PROMOTERS DRIVE EFFICIENT AND LONG-TERM TRANSGENE EXPRESSION IN THE CENTRAL NERVOUS SYSTEM

Recombinant adeno-associated viral vectors (rAAV) are used as gene therapy vectors to treat central nervous system (CNS) diseases. Despite their safety and broad tropism, important issues need to be corrected such as the limited payload capacity and the lack of small gene promoters providing long-term, pan-neuronal transgene expression in the CNS. Commonly used gene promoters are relatively large and can be repressed a few months after CNS transduction, risking the long-term performance of single-dose gene therapy applications. We used a whole-CNS screening approach based on systemic delivery of AAV-PHP.eB, iDisco+ tissue-clearing and light-sheet microscopy, to identify three small latency-associated promoters (LAP) from the herpesvirus pseudorabies virus (PRV). These promoters are LAP1 (404bp), LAP2 (498bp) and LAP1_2 (880bp). They drive chronic transcription of the virus encoded latency-associated transcript (LAT) during productive and latent phases of PRV infection. We observed stable, pan-neuronal transgene transcription and translation from AAV-LAP in the CNS for six months post AAV transduction. In several CNS areas, the number of cells expressing the transgene was higher for LAP2 than the large conventional EF1 promoter (1264bp). Our data suggests that the LAP are suitable candidates for viral vector-based CNS gene therapies requiring chronic transgene expression after one-time viral-vector administration.

neuroscience↗