# EM CORE

> **NIH NIH U19** · HARVARD UNIVERSITY · 2024 · $405,201

## Abstract

Electron Microscopy Core
The synaptic circuits that underlie vertebrate behavior are of interest to all of the investigators on this grant (and
neuroscientists more generally). Generating neural circuits in zebrafish is the principal goal of this core. Getting this
connectivity entails revealing four essential features of neural circuitry for each neuron: first, rendering its local input at
sufficient resolution to detect all the impinging synaptic connections, second, identifying the sign of these connections,
third, identifying the cells giving rise to this presynaptic input and fourth, identifying the postsynaptic cells innervated by
this neuron's axon. Ideally, these requirements need to be met for all the neurons in one vertebrate brain because without
this information, neuroscientists cannot accurately trace signals, synapse by synapse, from sensory input to motor output
-- a profound impediment to deciphering of how a brain's structure relates to its behavioral repertoire. Owing to the rapid
pace of technological and computational improvements, it is now feasible for the first time to create a whole vertebrate
animal connectional map. The methods we will use automate a serial section electron microscopy pipeline so that high
resolution (nanoscale) images can be acquired over large (millimeter scale) volumes. This core will use a modern
serial-section multibeam scanning electron microscopy approach that we have been developing for about 10 years 1 2 3 4 5 6
7 8 9 10 11 12 13 14 and combine this acquisition workflow with sophisticated image processing, leveraging machine learning
expertise and infrastructure at Google, the Advanced Physics Lab at Johns Hopkins, ground truth and proofreading taking
place in the Outreach and Training Core and the proofreading and manual tracing described in Project 3. One major
purpose of this Core is to assure that we do this integration successfully. One important aspect of this integration that will
make the connectional map more useful analytically, will be to oversee the technical aspects of the overlay of essential
fluorescence microscopy data derived from the same fish. This light microscopy-based data reveals whether neurons are
excitatory or inhibitory and the activity patterns of neurons during eight behaviors. We believe this Correlated Light and
Electron Microscopy (CLEM) will add powerful new dimensions to the analysis of the wiring diagram of a behaving
vertebrate.

## Key facts

- **NIH application ID:** 10918143
- **Project number:** 5U19NS104653-08
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Jeff W Lichtman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $405,201
- **Award type:** 5
- **Project period:** 2017-09-25 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918143

## Citation

> US National Institutes of Health, RePORTER application 10918143, EM CORE (5U19NS104653-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10918143. Licensed CC0.

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