# Produce the cell-type-specific thalamocortical projectome

> **NIH NIH U19** · ALLEN INSTITUTE · 2024 · $506,936

## Abstract

Summary, Project 2 (Produce the cell type-specific thalamocortical projectome)
Frontal cortex displays rich patterns of neural activity, which can be decomposed into 'activity modes'
corresponding to specific aspects of behavior (see Overall), such as the persistent activity correlated with short-
term memory, and rapidly cycling activity causing voluntary movements. Frontal cortex is strongly coupled to the
thalamus, the central hub of the forebrain. Subcortical information flows through the thalamus to the cortex. Most
of thalamus is non-sensory (‘higher-order’), with input from cerebellum, multiple parts of the midbrain, and
hippocampus, and outputs to most cortical areas (a detailed map of inputs is part of Project 1). This project aims
to uncover the thalamocortical (TC) cell types. These are excitatory neurons that receive input from subcortical
areas outside of the thalamus and project to the neocortex. Understanding TC types is critical because distinct
TC types likely correspond to specialized thalamocortical channels for transmission of information from sub-
cortex to cortex. We currently lack even a rudimentary conceptual framework for the function of non-primary-
sensory thalamus, in part because our knowledge of subcortex-thalamus-cortex circuits is at a nascent stage.
A limited set of morphological reconstructions have shown that the TC neurons are diverse across and within
thalamic nuclei defined by cytoarchitecture. Our preliminary data suggest that different control signals arise in
different subcortical areas, with distinct effects on cortical activity modes. The input-output rules at the level of
individual thalamocortical (TC) cells constrain the possible control strategies. Are subcortical control signals
routed through independent TC types or even different thalamic nuclei (‘labeled lines’)? Or do multiple subcortical
inputs converge at the level of TC cells, with individual TC types transmitting a mixture of control signals?
To help address these questions we will establish a census of TC types across the higher-order thalamus,
including neurons projecting to anterior lateral motor cortex (ALM) and medial prefrontal cortex (mPFC). We will
use new methods that combine morphological reconstructions of entire TC neurons with transcriptomics for the
same cells. We refer to cells defined in this manner as morpho-transcriptomic (m-t) TC types. We will further
densely map cell types defined by transcriptomics, so-called t-types, across the entire thalamus. By linking
morphology, transcriptomics and location at the single neuron level, these data will provide the foundation for
genetic access of specific TC types (strategies for genetic access will be developed in the Molecular Science
Core). Together, this information will create knowledge and tools for cell type-specific analysis of multi-regional
circuits (Projects 3, 4) with thalamus in the middle.

## Key facts

- **NIH application ID:** 10759418
- **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:** $506,936
- **Award type:** 5
- **Project period:** 2022-01-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10759418

## Citation

> US National Institutes of Health, RePORTER application 10759418, Produce the cell-type-specific thalamocortical projectome (5U19NS123714-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10759418. Licensed CC0.

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