# High-throughput Physiological Micro-connectivity Mapping in Vivo

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $83,909

## Abstract

PROJECT SUMMARY
Mapping the synaptic connectivity of brain circuits is essential for obtaining a mechanistic understanding of the
neural basis of behavior, learning, and cognition. While anatomical approaches can reveal the physical
architecture of neural circuits, only a functional approach can reveal the strength and dynamics of each synapse
in a network. These parameters are crucial for building any type of quantitative and explanatory model for how
neural circuits compute, encode, and store information. This proposal brings together three teams with
complementary expertise in holographic optogenetics and electrophysiology (Adesnik), high resolution
volumetric imaging (Ji) and statistical modeling and real-time experimental design (Paninski), to develop two
new technologies that will be able reveal much of the physiological connectome of single neurons in the brain.
The first approach combines high resolution multiphoton photo-stimulation in vivo with single cell intracellular
electrophysiology in the intact brain, and statistical algorithms that permit high-throughput mapping of the
targeted neuron's presynaptic connectome. The second approach employs the same photo-stimulation system,
but leverages optical reporters of activity in individual synapses to achieve the all-optical measurement of
synaptic connectivity in a cortical network chronically over time. These two new technologies will allow
neuroscientists to obtain the quantitative data on the physiological micro-connectivity of cortical networks across
large fractions of the cortex. The first approach provides unparalleled measurements of synaptic strength and
dynamics of each identified synaptic connections. The second approach permits the repeated assessment of
the micro-connectivity of the same neurons in the same animal over many days, finally opening up the
opportunity to map the reorganization of brain circuitry over the course of development, learning, or the
progression of brain disease.

## Key facts

- **NIH application ID:** 10387260
- **Project number:** 3RF1MH120680-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Hillel Adesnik
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $83,909
- **Award type:** 3
- **Project period:** 2021-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387260

## Citation

> US National Institutes of Health, RePORTER application 10387260, High-throughput Physiological Micro-connectivity Mapping in Vivo (3RF1MH120680-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10387260. Licensed CC0.

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