# Generating and accelerating the maturation of Pvalb-fast spiking interneurons from human stem cells

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $430,274

## Abstract

Multiple lines of evidence implicate dysfunction of cerebral cortical inhibitory interneurons in the
symptomatology of major neuropsychiatric illnesses, including schizophrenia, autism, Tourette disorder, bipolar
disorder, and epilepsy. This dysfunction involves subtypes of interneurons that differ in their neurochemistry,
connectivity, and physiological characteristics. Recent advances in the derivation of interneurons from human
pluripotent stem cells (PSCs) demonstrate their utility in studies of neuronal developmental genetics, function,
and disease. Unfortunately, there has been limited success at generating the parvalbumin-expressing, fast-
spiking (PV-FS) subgroup, even though this is the most plentiful subgroup of cortical interneuron and their
dysfunction is strongly implicated neuropsychiatric disease. Despite tremendous progress in enriching for
mouse embryonic stem cell (mESC)-derived PV-FS interneurons, no approach for enriching for their human
counterparts is available. This shortfall may be secondary to the length and complexity of human forebrain
neural subtype-specific directed differentiation protocols, but also to the protracted maturation of PV-FS cells
that normally require strong excitatory inputs to mature.
 The goal of this highly focused, 3-year, modular budget, renewal application is to build directly upon our
substantial progress in deriving PV-FS from mESCs the previous grant cycle, together with our progress at
accelerating the maturation of human stem cell derived interneuron-like cells by conditional activation of mTOR
signaling, to enrich for the derivation of PV-FS interneurons from human PSCs. Through this scalable process
we will also establish experimental systems, including co-culture with prenatal rat cortical neurons and
astrocytes, transplantation into neonatal mouse neocortex, and engraftment into human forebrain organoids,
that will enable complimentary scientific questions to be addressed. Success in this endeavor will make
possible a host of future studies on the etiology, prevention, and treatment of interneuron-related
neuropsychiatric disease.

## Key facts

- **NIH application ID:** 9895850
- **Project number:** 5R01MH066912-17
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Stewart A Anderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $430,274
- **Award type:** 5
- **Project period:** 2003-01-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895850

## Citation

> US National Institutes of Health, RePORTER application 9895850, Generating and accelerating the maturation of Pvalb-fast spiking interneurons from human stem cells (5R01MH066912-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895850. Licensed CC0.

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