New optical probes allow ultrafast imaging of dopamine activity in the brain

June 4, 2018 by Carole Gan, UC Davis
A transformative technology has enabled UC Davis neuroscientists to capture when and when dopamine activity occurs in the brain within milliseconds and at the cellular level, producing a high-resolution map of dopamine transients associated with behaviors such as learning. Credit: Laboratory of Lin Tian at UC Davis

UC Davis neuroscientist Lin Tian and her team, Tommaso Patriarchi, Gerard Broussard and Ruqiang Liang, have developed fluorescence sensors that are opening a new era for the optical recording of dopamine activity in the living brain.

The technology precisely captures where and when activity occurs in the brain within milliseconds and at the cellular level, producing a high-resolution map of dopamine transients associated with behaviors, such as learning.

A broad application of this tool will further understanding of dopamine activity underlying motivation, reward and movement, and pave the way to discover effective and novel therapeutics for depression, addiction and .

Their work published May 31 as a First Release in the prestigious journal Science.

Video provides an overview of new optical probes developed in the laboratory of Lin Tian at UC Davis and its importance to discovering effective and novel therapeutics for depression, addiction and drug abuse. Credit: Laboratory of Lin Tian at UC Davis
What is the current knowledge about the brain and its circuitry, and what don't we know?

The brain's "wiring" contains billions of neurons interconnected by trillions of synapses, the space between the end of a nerve cell and another cell that allows the transmission of impulses by chemicals called neurotransmitters. Electrophysiology and imaging studies have provided details on the structure and function of nerve cells and how an action potential at the synapse allows the transmission of signals that govern essential functions, from learning, memory and behavior to movement and sensations. But what we don't understand as well is what is happening at the molecular level and which factors, conditions and chemical levels drive neurotransmitter release at the synapse.

Why is understanding brain circuitry important?

Altered dynamics of neurotransmitters and neuromodulators are associated with a number of neurological and psychiatric diseases, including Parkinson's disease, schizophrenia and addiction. Hence, drugs that mimic or block neuromodulators have become important components in the treatment of these disorders. The , for example, plays an important role in movement, attention, learning and the brain's pleasure and reward system. Mental illnesses, such as depression, can occur when this process isn't working correctly.

Although neuroscientists have discovered more than 100 neurotransmitters and neuromodulators and detailed their structure and function, we don't know the precise mechanisms by which these molecules regulate the dynamics of healthy and diseased neural circuitry. Linking complex neural phenomena to the structure and function of their composite requires a thorough understanding of patterns of neural activity, and the ability to relate this to physiological processes and behavior.

Would you summarize your study published in Science?

We report the development of the first class of fluorescent protein-based optical dopamine (DA) indicators, which we named dLight1, capable of directly reporting spatial and temporal release of DA with high-resolution both in vitro and in vivo. By labeling a specific neuronal population in living animals, we now can track the dynamic change of released dopamine that occurs within milliseconds and at during specific activities, such as running and reward learning. dLight overcomes major barriers in the field, and dramatically increases the resolution that we can measure dopamine in the brain of behaving mice. This technology is a game-changer. It can record spatioltemporal coding of dopamine in the brain (creating dopamine-transient map) in high resolution that codes motivation, movement, learning and drug abuse.

We can leverage these tools to develop sensors for other neuromodulators, including norepinephrine, serotonin, melatonin and opioid neuropeptides. This toolset offers the ability to gain vital information about release sites and kinetics for these endogenous ligands, thus open a new era for developing effective drugs for neurological disorders and revealing brain functions that underly motivation, movement, learning and drug abuse.

Why is this study important?

Our specially designed sensors combined with optical imaging techniques provides a powerful tool for analyzing and engineering functional neural circuits associated with learning, memory, behavior and disease states. We can leverage these tools to develop sensors for other neuromodulators, including norepinephrine, serotonin, melatonin and opioid neuropeptides and to empower the search for novel therapeutic treatments.

Explore further: Study in mice identifies the molecular machinery responsible for dopamine release in the brain

More information: Tommaso Patriarchi et al. Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors, Science (2018). DOI: 10.1126/science.aat4422

Related Stories

Study in mice identifies the molecular machinery responsible for dopamine release in the brain

February 1, 2018
Studied for decades for its critical role in movement control and reward-seeking behaviors, the neurotransmitter dopamine has been the focus of numerous efforts to understand its activity, particularly when it goes awry in ...

Dopamine, drugs, and depression

February 1, 2018
The neurotransmitter dopamine plays a major role in mental illnesses like substance abuse disorders and depressive disorders, as well as a more general role in reward and motivational systems of the brain. But there are still ...

Researchers confirm important brain reward pathway

November 12, 2014
Details of the role of glutamate, the brain's excitatory chemical, in a drug reward pathway have been identified for the first time.

Delving deep into the brain

May 1, 2014
Launched in 2013, the national BRAIN Initiative aims to revolutionize our understanding of cognition by mapping the activity of every neuron in the human brain, revealing how brain circuits interact to create memories, learn ...

Impulsivity in Parkinson's disease

October 30, 2017
Dopamine medications are effective in treating the motor symptoms of Parkinson's disease (PD), but dopamine agonists can trigger impulsive-compulsive behaviors (ICBs), such as compulsive gambling, eating or shopping, in a ...

Brain health researchers delve into dopamine

August 25, 2017
University of Otago researchers studying learning processes affected in brain disorders such as Parkinson's disease and Attention Deficit Hyperactivity Disorder (ADHD) have made new discoveries about how nerve impulses form ...

Recommended for you

Cell study reveals how head injuries lead to serious brain diseases

November 16, 2018
UCLA biologists have discovered how head injuries adversely affect individual cells and genes that can lead to serious brain disorders. The life scientists provide the first cell "atlas" of the hippocampus—the part of the ...

Newborn babies' brain responses to being touched on the face measured for the first time

November 16, 2018
A newborn baby's brain responds to being touched on the face, according to new research co-led by UCL.

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful

November 14, 2018
Expect a shot to hurt and it probably will, even if the needle poke isn't really so painful. Brace for a second shot and you'll likely flinch again, even though—second time around—you should know better.

A 15-minute scan could help diagnose brain damage in newborns

November 14, 2018
A 15-minute scan could help diagnose brain damage in babies up to two years earlier than current methods.

New clues to the origin and progression of multiple sclerosis

November 13, 2018
Mapping of a certain group of cells, known as oligodendrocytes, in the central nervous system of a mouse model of multiple sclerosis (MS), shows that they might have a significant role in the development of the disease. The ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.