# Molecular Science Core

> **NIH NIH U19** · ALLEN INSTITUTE · 2024 · $389,339

## Abstract

Summary, Molecular Science Core
The thalamus contains excitatory neurons that receive input from diverse areas outside of the thalamus
(neocortex, cerebellum, basal ganglia, midbrain, hippocampus) and project to the neocortex. Recent molecular
mapping and morphological reconstructions have shown that these thalamocortical (TC) cells are much more
diverse than previously thought, both across and within cytoarchitectonically-defined thalamic nuclei. Different
TC cells likely receive input from different subcortical structures, and project to different cortical areas and layers.
Experimental access to specific TC cell types is essential for elucidating their roles in neural circuit function.
Single cell genomics has recently enabled unprecedented definition of cell types at the molecular level and has
uncovered numerous marker genes and putative regulatory elements, which can be used to generate genetic
tools for access to specific cell populations.
For the adult mouse thalamus, we have generated a large-scale single-cell transcriptomics dataset (scRNA-seq)
to measure gene expression, and a matching single-nucleus chromatin accessibility dataset (snATAC-seq) to
discover putative enhancers. In addition, we are in the process of generating equivalent data for the developing
mouse thalamus. These datasets will enable us to select marker genes and enhancers to generate transgenic
and viral tools for genetic access to TC types. To refine access to specific TC types, intersectional genetic
approaches combining viruses, transgenes, and retrograde labeling will be explored. We will evaluate the
completeness of labeling a specific cell population versus specificity at the level of the whole brain, as different
levels of specificity / completeness are needed for different experimental purposes. Sparse yet specific labeling
is ideal for morphological examination, whereas relatively complete and locally or globally specific labeling is
needed for behavioral perturbations.
The tools will be used in other research segments (Projects 2, 3, 4) as soon as they become available. Tool
characterization will combine standardized Allen Institute pipelines: whole-brain cellular imaging, multiplexed
fluorescence in situ hybridization (mFISH), as well as scRNA-seq. DNA constructs, transgenic mice, virus
packaging techniques, recommended virus titers, and virus and transgene characterization data will be made
available in public repositories.

## Key facts

- **NIH application ID:** 10759414
- **Project number:** 5U19NS123714-03
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Bosiljka Tasic
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $389,339
- **Award type:** 5
- **Project period:** 2022-01-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10759414

## Citation

> US National Institutes of Health, RePORTER application 10759414, Molecular Science Core (5U19NS123714-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10759414. Licensed CC0.

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