# Chandellier interneurons and the excitation/inhibition balance in the human prefrontal cortex in autism

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $381,489

## Abstract

Chandellier interneurons and the excitation/inhibition balance in the human prefrontal cortex in autism
Little is known about the pathology of the cerebral cortex in autism. The goal of our previously funded R01
grant was to unravel the pathology of the cerebral cortex in patients with autism. Specifically, we proposed to
discover which cell type(s), if any, are altered in the cerebral cortex of human autistic cases. We quantified the
number of pyramidal neurons, specific subtypes of interneurons, and glial cells, within each layer of the human
temporal and prefrontal cortex in autism. We determined that the number of pyramidal neurons and glial cells
in the temporal cerebral cortex of autistic cases did not differ from that in typically developing control cases,
and published our results in several research articles (Camacho et al., 2014; Kim et al., 2015). However, we
discovered that there is a decrease in the number of one specific interneuronal subtype in the prefrontal cortex
of autistic cases, the parvalbumin (PV)+ Chandellier cell (Hashemi et al., 2016). Chandellier (Ch) cells are the
main interneuron in the cortex possessing axons that synapse directly on the initial segment of the pyramidal
axon, creating a prominent structure called “cartridge”. Consequently, the Ch cell is the main interneuronal
subtype that regulates the final output of excitatory projection neurons. Therefore, the loss of a small number of
Ch cells may critically impair function of pyramidal cells and of the cerebral cortex as a whole. Indeed, changes
in Ch cells cartridges/boutons and/or function have previously been reported in neurological diseases, such as
schizophrenia and epilepsy. Based on our discovery, we propose to define the role of Ch cells in autism by
unraveling their morphological and connectional properties.
We hypothesize that the decreased number of PV+ Ch cells we discovered in the autistic cortex translates into
a decrease in the number of Ch cell cartridges and a decrease in the number of synaptic buttons per cartridge,
with the consequent loss of Ch symmetric synapses on the pyramidal neuron axonal initial segment, and
ultimately impaired function of cortical projection neurons. We also hypothesize that there is a decreased
amount of GABA and GABA related proteins per cartridge, and of GABRAα2 receptors in the pyramidal axonal
initial segment. This reduction of inhibitory synapse structure would cause hyperexcitation of cortical synaptic
circuits in autism. Additionally, we hypothesize that in autism there is a negative correlation between the
severity of the patient' symptoms and the number of Ch cells.
We will determine if there is an alteration in the number and length of Ch cell cartridges (Aim1), if there is an
alteration in the GABAergic system in Ch cartridges (Aim 2), and if there is an alteration in the number of axo-
axonic synapses (Aim 3) in the prefrontal cortex (BA9, BA45, BA46) of the autism postmortem brain. We will
label cartrid...

## Key facts

- **NIH application ID:** 9989893
- **Project number:** 5R01MH094681-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Veronica Martinez-Cerdeno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,489
- **Award type:** 5
- **Project period:** 2011-06-02 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989893

## Citation

> US National Institutes of Health, RePORTER application 9989893, Chandellier interneurons and the excitation/inhibition balance in the human prefrontal cortex in autism (5R01MH094681-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9989893. Licensed CC0.

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