Biology subjects

Stafford, D. A.

Publications and source records attributed to Stafford, D. A..

3 recordsLinked to original sources

bioRxiv2024

A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types

The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We used transcriptomic and epigenomic cortical cell type taxonomies from mouse and human to define marker genes and putative enhancers and created a large toolkit of transgenic lines and enhancer AAVs for selective targeting of cortical cell populations. We report evaluation of fifteen new transgenic driver lines, two new reporter lines, and >800 different enhancer AAVs covering most subclasses of cortical cells. The tools reported here as well as the scaled process of tool creation and modification enable diverse experimental strategies towards understanding mammalian cortex and brain function.

molecular biology↗

bioRxiv2024

Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity

Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their "volume transmission" output property. However, their activity and function within cortical circuits remain unclear. Here, we developed two genetic tools to target these neurons and examine their function in the primary visual cortex. We found that the spontaneous activity of neurogliaform cells positively correlated with locomotion. Silencing these neurons increased spontaneous activity during locomotion and impaired visual responses in L2/3 pyramidal neurons. Furthermore, the contrast-dependent visual response of neurogliaform cells varies with their laminar location and is constrained by their morphology and input connectivity. These findings demonstrate the importance of neurogliaform cells in regulating cortical behavioral state-dependent spontaneous activity and indicate that their functional engagement during visual stimuli is influenced by their laminar positioning and connectivity.

neuroscience↗

bioRxiv2022

Cortical somatostatin interneuron subtypes form cell-type specific circuits

The cardinal interneuron classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings glosses over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron class. The organizing principles by which the connectivity of these subtypes is specified are unknown. To address this knowledge gap, we designed a series of genetic strategies to target the breadth of somatostatin interneuron subtypes. Using these strategies to target three subtypes that span the entire cortical column, we examined their afferent and efferent connectivity. Our data demonstrated that each of these possesses remarkable reciprocal connectivity with the intracortical or corticofugal pyramidal classes, as well as parvalbumin interneurons. Even when two interneuron subtypes shared the same efferent target, their synaptic targeting proved selective for particular dendritic compartments. We thus provide evidence that subtypes of somatostatin cortical interneurons form cell-type specific cortical circuits.

neuroscience↗