# A Functional Taxonomy of Cortical Astrocytes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $340,990

## Abstract

A Functional Taxonomy of Cortical Astrocytes
 The vast majority of neural circuit studies neglect to take into account the non-neuronal
cells in the brain, but in order to truly appreciate neural circuit function, we will need to monitor
and manipulate activity in many cell types. Our understanding of astrocyte signaling is years
behind that of neurons, because the appropriate tools have been lacking for these largely
electrically silent cells. We don't know what extracellular signals astrocytes respond to, nor how
they contribute to circuit function. This is due, in part, to the lack of methods that replicate the
breadth of possible presynaptic activity in vivo, i.e. the release of neurotransmitter. The current
proposal addresses gaps in our understanding of astrocytes in neural circuit function and
harnesses the power of light-activatable tools to tackle them. We propose to apply a suite of
optochemical tools that allow spatiotemporally precise and physiologically relevant release of
neurotransmitter to astrocytes and neurons in cortical circuits.
 In Aim 1, we will test the hypothesis that astrocytes response acutely to the synaptic
release of excitatory and inhibitory synaptic activity with differential and predictable activity. We
will use simultaneous two-photon optochemical uncaging and calcium imaging in astrocyte
branches to test their physiological response to glutamatergic and GABAergic synaptic events,
and uncover the heterogeneity of molecular mechanisms that govern these responses. We will
activate astrocytes in vivo using these optochemical techniques, and in Aim 2, genetically
silence astrocyte-specific excitatory and inhibitory receptors during in vivo imaging and
electrophysiology to determine the astrocytic signals that lead to downstream cortical state
shifts. In Aim 3, we will validate novel optochemical tools to mimic the release of
neuromodulators in the cortical circuit, testing their function in neurons and astrocytes. With
these tools in hand, we will be able to probe the repertoire of signals to which astrocytes
respond in the circuit.

## Key facts

- **NIH application ID:** 10059277
- **Project number:** 5R01NS099254-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Kira Poskanzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $340,990
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10059277

## Citation

> US National Institutes of Health, RePORTER application 10059277, A Functional Taxonomy of Cortical Astrocytes (5R01NS099254-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10059277. Licensed CC0.

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