# CACNB4 overexpression and a mechanism for dendritic spine loss in schizophrenia

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $18,372

## Abstract

PROJECT SUMMARY/ABSTRACT
Schizophrenia (Sz) is a chronic illness with prominent synaptic pathology and a leading cause of disability.
Dendritic spine density is reduced in Sz in layer III of primary auditory cortex (A1). Spine loss in A1 in Sz is
thought to underlie auditory sensory processing deficits and in turn contribute to socio-cognitive dysfunction,
which is associated with the poorest functional outcomes among individuals with Sz. Recently our lab determined
that spine reductions in A1 in Sz are selective for loss of small, presumably new dendritic spines. The goal of
this training fellowship is to explore a potential molecular mechanism for small dendritic spine loss, like
observed in A1 in Sz. Our lab recently demonstrated that small spine loss in A1 is associated with increased
levels of the β subunit, an auxiliary subunit of voltage gated calcium channels (VGCCs). β subunits regulate the
activity of VGCCs: they promote surface expression of channel-forming subunits, regulate channel gating, and
facilitate Gbl-, RGK-, phospho- and lipid-mediated inhibition. Overexpressing CACNB4, which encodes β4,
reduced small, but not large spines in vitro, proof-of-concept that increased β4 levels could drive the small spine
loss observed in A1 in Sz. β4 is a candidate protein for the loss of small, presumably new dendritic spines
in A1 in Sz. Auxiliary subunits differentially regulate high voltage activated (HVA) and low voltage activated (T-
type) VGCCs. Emerging evidence suggests that β subunits can interact with and gate T-type VGCCs25-28.
Blocking T-type but not HVA VGCCs impeded the assembly of new dendritic spines2. The experiments in this
proposal will test the hypothesis that small spine loss is due to β4-mediated decrease in T-type VGCC
function and impaired new spine assembly. During this training fellowship I will receive excellent training in
Sz neurobiology, cell and slice culture, patch clamp electrophysiology, Ca2+ and live cell imaging methods from
experts in the field. Even if I am not able to accept my central hypothesis, these data collected from these
experiments will provide novel and important information about the regulation of T-type VGCCs and β4
modulation of spine dynamics. Additionally, these data have the potential to inform the development of innovative
pharmacological interventions for auditory processing deficits and socio-cognitive dysfunction in Sz.

## Key facts

- **NIH application ID:** 9974281
- **Project number:** 5F31MH117834-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Emily Meredith Parker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $18,372
- **Award type:** 5
- **Project period:** 2019-07-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974281

## Citation

> US National Institutes of Health, RePORTER application 9974281, CACNB4 overexpression and a mechanism for dendritic spine loss in schizophrenia (5F31MH117834-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974281. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*