# Single-cell computation in auditory brainstem and its impact on cortical coding and behavior

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $2,866,755

## Abstract

Project Abstract
Understanding how neuronal computations build up a perception of the external world is fundamental to our
understanding of how the brain works. This is particularly relevant to sensory systems, where heterogenous
inputs representing distinct sensory features must be re-assembled to generate a perception. How individual
neurons in early stages of sensory circuits process parallel inputs, and how these circuit elements later contribute
to cortical computations that bind the inputs together is completely unknown. Studies have demonstrated that
the timing, position and strength of a given input along the dendrite of a given neuron is a critical strategy used
by the brain to encode sensory features. However, how such dendritic integrations of inputs in single neurons
contribute to an animal's overall perception is not understood.
To re-assemble diverse features from the same initial stimulus, the brain needs to determine which features
occurred at the same time. Currently, little is known about how or where this timing information might be encoded.
The auditory system offers an ideal system to tackle this question based on its tractability to interdisciplinary
methods and its known ability to encode even miniscule differences in timing. Specifically, we will take advantage
of a unique cell type in the auditory cochlear nucleus, called octopus cells, as a model to investigate the question
of how small cell classes contribute to behavioral and perceptual circuits. Octopus cells are prominent in all
mammalian species and are well known to encode temporal inputs with submillisecond precision through
integration of primary sensory inputs along their large and extensive dendrites. We propose to carry out a multi-
lab, integrated analysis of the molecular and biophysical properties of octopus cells and to track how these single
cell computations are transformed along the auditory pathway to contribute to an animal's final auditory percept
and hence behavior. Using the mouse as a model system, we will apply new sequencing methods together with
high resolution brain imaging and single cell reconstructions to create a comprehensive wiring diagram of
octopus cells and their auditory inputs. By generating mouse strains for selective access to octopus cells, we will
be ideally positioned to investigate the in vitro and in vivo physiology of octopus cells and therefore bridge
experimental and computational models for how timing information is encoded at the single cell level. Lastly, we
will study how timing information propagates to higher auditory centers by recording from large populations of
neurons in the midbrain, thalamus, and cortex and then assessing the functional relevance of temporal coding
for auditory behavior. By leveraging molecular, biophysical, electrophysiological, behavioral, and computational
approaches toward the study of this model cell type, these studies will allow us to extract general principles of
single cell computation...

## Key facts

- **NIH application ID:** 10050683
- **Project number:** 1R01NS118402-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Nace L Golding
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,866,755
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050683

## Citation

> US National Institutes of Health, RePORTER application 10050683, Single-cell computation in auditory brainstem and its impact on cortical coding and behavior (1R01NS118402-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10050683. Licensed CC0.

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