Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species.

Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have revealed substantial diversity of glial cells, particularly astrocytes. To better understand glial cell types and their roles in neurobiology, we built a new suite of adeno-associated viral (AAV)-based genetic tools to enable genetic access to astrocytes and oligodendrocytes. These oligodendrocyte and astrocyte enhancer-AAVs are highly specific (usually > 95% cell type specificity) with variable expression levels, and our astrocyte enhancer-AAVs show multiple distinct expression patterns reflecting the spatial distribution of astrocyte cell types. To provide the best glial-specific functional tools, several enhancer-AAVs were: optimized for higher expression levels, shown to be functional and specific in rat and macaque, shown to maintain specific activity in epilepsy where traditional promoters changed activity, and used to drive functional transgenes in astrocytes including Cre recombinase and acetylcholine-responsive sensor iAChSnFR. The astrocyte-specific iAChSnFR revealed a clear reward-dependent acetylcholine response in astrocytes of the nucleus accumbens during reinforcement learning. Together, this collection of glial enhancer-AAVs will enable characterization of astrocyte and oligodendrocyte populations and their roles across species, disease states, and behavioral epochs.

Parallel regulation of past, present, and future actions during sequencing.

Past, present, and future actions must be regulated online to produce sequences of actions, but the regulation process is not well understood because of measurement limitations. We provide the first direct tests of the parallel action regulation hypothesis during sequencing in humans. We used transcranial magnetic stimulation to probe the level of excitation for flexion of the right index finger during typing. Motor evoked potentials (MEPs) were recorded at the onset of typing 5-letter words and nonwords. A single letter typed by the right index finger varied across letter positions 1 to 5. MEP amplitude was largest for the upcoming action in the second position and decreased monotonically across future serial positions, suggesting a serial inhibition process regulates all future actions in parallel during sequencing. This is the most direct human evidence to date corroborating models of sequence production that assume parallel regulation of actions. (PsycINFO Database Record