# Development of the Calyx of Held

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2024 · $687,951

## Abstract

Project Summary:
A hallmark of developing neural systems is the guidance by spontaneous and experience-driven neural
activity for strengthening of some synaptic inputs and pruning of others to define topography of mature
neural circuits. We and others have established formation of the calyx of Held (CH) and its innervation of
principal neurons (PN) in the medial nucleus of the trapezoid body as a model system to study neural circuit
development. We showed that that the CH:PN system, relative to other model systems, has precise onset
and short duration of strengthening and pruning to a topographically mature circuit by postnatal day 9, prior
to ear canal opening. Preliminary data demonstrates that suppression of spontaneous activity (SA) targeted
to the CH:PN synapse prevents key aspects of PN functional maturation.
 In this proposal we capitalize on this observation to define the functional and structural elements of
circuit construction so that we can identify those maturational events that depend on SA. Our research team
brings extensive experience with biophysical and physiological properties of this system, which we examine
at high (daily) temporal resolution. We leverage our experience with imaging and reconstruction of large
electron microscopy volumes to specify global aspects of initial circuit topography along with subcellular
detail as a precise structural framework to anchor our observations. We next explore cellular and molecular
mechanisms that transmit information about neural activity to maturational programs at high temporal
resolution, focused upon activity-dependent Ca2+ entry and phosphorylation of the constitutive transcription
factor CREB. These accumulated data can be correlated with better temporal precision than in other model
systems to provide deeper insight into causal relationships between SA and maturational events. Errors in
early neural circuit specification can result in generalized intellectual and social disabilities, which can have
auditory specific phenotypes as in autism spectrum disorders.

## Key facts

- **NIH application ID:** 10905432
- **Project number:** 2R01DC007695-12
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** GEORGE A SPIROU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $687,951
- **Award type:** 2
- **Project period:** 2007-06-13 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10905432

## Citation

> US National Institutes of Health, RePORTER application 10905432, Development of the Calyx of Held (2R01DC007695-12). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10905432. Licensed CC0.

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