The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.

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Shared and distinct transcriptomic cell types across neocortical areas

Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1 × 1011 vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1 × 1012 vg of AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons. The efficiency of these vectors facilitates robust cotransduction and stochastic, multicolor labeling for individual cell morphology studies. To support such efforts, we provide methods for labeling a tunable fraction of cells without compromising color diversity. Furthermore, when used with cell-type-specific promoters and enhancers, these AAVs enable efficient and targetable genetic modification of cells throughout the nervous system of transgenic and non-transgenic animals.

/pdf/engineered-aavs-for-efficient-noninvasive-gene-delivery-to-598nspvqwi.pdf

Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

Modern optogenetics can be tuned to evoke activity that corresponds to naturally occurring local or global activity in timing, magnitude or individual-cell patterning. This outcome has been facilitated not only by the development of core features of optogenetics over the past 10 years (microbial-opsin variants, opsin-targeting strategies and light-targeting devices) but also by the recent integration of optogenetics with complementary technologies, spanning electrophysiology, activity imaging and anatomical methods for structural and molecular analysis. This integrated approach now supports optogenetic identification of the native, necessary and sufficient causal underpinnings of physiology and behaviour on acute or chronic timescales and across cellular, circuit-level or brain-wide spatial scales.

/pdf/integration-of-optogenetics-with-complementary-methodologies-54nct3rloa.pdf

Integration of optogenetics with complementary methodologies in systems neuroscience

AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.

A Neural Circuit for Gut-Induced Reward.

A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons.

The present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater infectivity of a cardiac cell compared to wild-type AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a cardiac cell in an individual. The present disclosure provides methods of generating an induced cardiomyocyte-like cell. The present disclosure provides methods of editing the genome of a cardiac cell.

Adeno-associated virus with variant capsid and methods of use thereof

La presente invention concerne des virions de virus adeno-associe recombine (rAAV) comprenant un variant de proteine de capside d'AAV, par exemple, une proteine de capside d'AAV derivee d'une sequence d'acides amines de proteine de capside d'AAV ancestral. Un virion de rAAV selon la presente invention peut presenter une plus grande infectivite d'une cellule cible. La presente invention concerne egalement des procedes d'administration d'un produit genetique a une cellule cible chez un individu par l'administration a l'individu d'un rAAV de la presente invention. La presente invention concerne egalement des procedes permettant de generer des virions de rAAV qui ont un variant de proteine de capside d'AAV derivee d'une sequence d'acides amines de proteine de capside d'AAV ancestral.

David Stephen Ojala

Papers

A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons.

Adeno-associated virus with variant capsid and methods of use thereof

Variants de virus adéno-associé et leurs procédés d'utilisation