Shining light on the neurons that make you move

Science Stories: Shining light on the neurons that make you move

Author: Marie Labouesse, Post-doctoral Research Fellow in the Department of Psychiatry. Marie studies the neuronal circuits that regulate movement deep inside the brain


Parkinson’s disease is a devastating neurological disorder characterized by severe impairments in motor control. One of the key pathological features of Parkinson’s disease is the gradual cell death of dopamine neurons deep inside the brain. However, dopamine neurons are not the only actors in the picture. In this short story, you will learn about how dopamine neurons communicate through far reaching axon “bridges” with other neurons at the front of the brain to control movement in a coordinated matter.

“Hey Julie, I’ve always wondered why exactly do the hands of our neighbor shake like that? You study this in lab, right?” asked Tom to Julie on their way to work, as they were crossing Roberto in the street. Tom and Julie were both postdocs, but Tom studied plant biology while Julie was a neuroscientist studying animal models of Parkinson’s disease.

“Well- I don’t exactly study Parkinson’s disease (PD), Tom. But I can tell you what I know. Patients with PD have different symptoms, one of which is called tremor, like Roberto having shaky hands. Another major symptom is called bradykinesia, which refers to the inability to start basic movements, for example walking or tying up shoe laces.

All this is due to a problem happening deep inside the brain. The brain contains about 200 billion cells, 100 billion of which are neurons. Each of these neurons has their own hardrive – the nucleus – that dictates their role in the brain. First, they will each get activated by specific signals: some of them light up if you are hungry or stressed, others get activated by rewarding events or by decisions coming down from the cortex. In turn, neurons will trigger specific responses, like promote movement, help you remember things or help you find food.”

Example of neuronal types

“So which ones are damaged in Roberto’s brain? The ones that make you move?” asked Tom.

“In fact no, the so-called movement neurons are still there in Roberto’s brain. Another type of neuron, known as dopamine neurons, are the ones that die in PD. Dopamine neurons get activated when something new and unexpected is happening, or something rewarding or important. They basically help you pay attention or learn what is worth your time and energy, and in turn they facilitate movements. For example, if your bus is arriving unexpectedly early, your dopamine neurons will light up immediately and help facilitate you running towards the bus. Basically think of dopamine neurons as the steam of your engine, while movement neurons are the wheels of your car, both are crucial.

“So are you trying to find a cure for this?” said Tom.

“No, I’m more in the basic science side of things, I try to understand how the system works when everything is going right. Hopefully it will help other scientists understand what happens when the system is broken and how you might be able to fix things.”

“OK. That makes sense, but then what do you study?” asked Tom.

“You want the full story? So, you see, in PD, dopamine neurons slowly undergo cell death. We don’t fully know why- other scientists are working on this.

From dopamine neurons to movement neurons: the neural circuit of movement

Dopamine neurons are found more or less half-way between your eyes and the back of your head. We call this the midbrain, said Julie. They are also very long. Of course their central part, the nucleus and cytosol, remain in the midbrain. However, to send information to other neurons at distant locations, they use axons which are kind of like highway bridges between two islands. Just like the Brooklyn Bridge between Manhattan and Brooklyn.”

“Which other neurons do the dopamine-neurons talk to in front of the brain, then? Is it the movement neurons?”, said Tom.

“Yes, the movement neurons, exactly. Dopamine neurons in the midbrain communicate with movement neurons that live all the way in the front of the brain – in an area called the striatum. As we said, dopamine neurons get lit up by new or important events, say you’re playing basketball, and someone passes the ball over to you. In response to this event, dopamine neurons are activated and start firing. This basically means there is suddenly a flow of electric charges throughout the neuron’s membranes, all the way throughout the axon. We call this particular flow of electric charges an action potential.

It’s similar to an electric circuit where you’d activate the switch and electrons start circulating. In a neuron, the electric charges can reach all the way throughout the axon and into the axon’s endfeet, also known as synapses. At the synapse, several cellular processes will then be activated by the arrival of these electric charges or action potential. These processes are “electrically-dependent”, just like you’ll need electricity to turn on a lamp that lies in your electric circuit. One of these key synaptic processes is called synaptic transmission, which basically means chemicals will be released from the synapse in the presence of electric charges, and in turn these chemicals can now transmit information to other neurons lying nearby! These chemicals are rightly so called “neurotransmitters”.

Synaptic transmission at dopaminergic synapses

The type of neurotransmitter will depend on the neuron’s identity. For example in dopamine neurons, synapses release primarily dopamine. And this is the key: movement neurons in the striatum express receptors for dopamine! So when dopamine neurons release dopamine, this will activate movement neurons. In turn, movement neurons will hand over the message to a set of other neurons through a very specialized circuit. Eventually this circuit transmits the signal directly to the muscles in your arms and instruct them to move.”

“Ok this makes sense. So Roberto’s movement neurons and all the circuit downstream is still functional, right? So why is he not able to control his movements then?

“This is where it gets a bit complicated: Roberto does have the movement neurons as well as the circuits downstream of that. As you said, this works more or less OK (although this is also debatable, but that story is for another day). The main problem to keep in mind is that the message from dopamine neurons is not being properly transmitted to movement neurons. Actually, let me step back for a bit. There are actually not just one, but actually two types of movement neurons: the first type are called #go neurons, and the second type are called #stop neurons. So when dopamine neurons send their message out to #go and #stop neurons, they are going to have an opposite effect on them. It’s kind of like when I use my forward and my brake pedals in the car. I am doing the same movement with my feet, a.k.a. I press a pedal. But when I press the forward pedal, my car will move forward, whereas when I press the brake pedal, I stop!

Same here: when dopamine neurons transfer their message to #go neurons, this will promote movement (as I told you above), whereas when dopamine neurons transfer their message to #stop neurons, this inhibits movement.”

“Ok, so we basically turn on #go neurons when we want to start moving and #stop neurons when we want to pause?”

Coordinated activity between stop and go neurons?

“Well, that’s what we all thought happened until about 10 years ago, so you are pretty close to the truth! But now scientists think it’s actually more complicated than that. These #go and #stop neurons can actually receive messages from many other neurons, in particular the cortex, i.e. the master-controller of your brain. Recent work has shown that when you start moving, both #go and #stop neurons are actually lit up at the same time. This idea was quite revolutionary when it first arrived. One of the current hypothesis is that #go neurons might help you to accomplish the movements you want to do, for example moving your feet in the direction of the bus. On the other hand, #stop neurons will block the movements that are unnecessary, like starting to tie your shoe lace at the same time. This might actually be at the level of more refined movements, like moving your right leg forward, but pausing your left one for a few milliseconds, in order to perform the basic movement of walking.

“What if I am tying my shoes, and then the bus arrives. How do #go neurons and #stop neurons synchronize themselves to switch from one task to the next? Like, how do I not trip myself over?!”, asked Tom, perplex.

“Well that’s exactly what I am studying: it seems like #go and #stop neurons are able to communicate to make sure they are on the same page and that all movements are made in harmony! However, we don’t know yet the full mechanisms by which they communicate or what other partners are involved, that’s what I am looking into.”

“Ok- nice, and how exactly do you study this?”, asked Tom.

“I use two main approaches. The first one is called optogenetics, it was invented only about 15 years ago. It’s a ground-breaking technique that allows to activate or shut off specific neural populations with light. In my case, I want to activate movement neurons. To do that, I use light-sensitive molecules that allow electric charges to enter neurons when exposed to light. Remember, changes in electric charges can promote synaptic transmission and allow neurons to perform their function. Importantly, I can insert these light-sensitive molecules specifically into #go or #stop movement neurons using genetic tools and specific mouse models. And then it’s amazing, I can have mice running around in motor behavioral tasks and once I shine light deep into the brain, I will be able to activate movement neurons at specific moments in the task, allowing me to determine the effects of #go or #stop neuron activation on movement.

Methods to activate or record activity from specific neuronal populations

The other approach is known as calcium imaging. It allows me to record the activity of neurons online while mice are performing motor tasks. The reason for this is that when neurons are active, levels of calcium within the cells change at high speed. Tracking calcium levels is therefore a good method to follow the activity of neurons. Technically-speaking, it is similar than optogenetics, except the molecules used will be sensitive to calcium, rather than light. Thanks to calcium imaging, I am able to see how #go and #stop neurons coordinate their activities live during movement.”

“Sounds very exciting. So how will this eventually help Roberto?”, asked Tom.

“Great question. Well the idea is that if we understand the circuits well, we can then go ahead and design better treatments which are more specific. For example, one treatment currently used to help people dealing with Parkinson’s disease is called Deep Brain Stimulation, where patients receive electrical stimulation of a brain area close to the midbrain. If we understand how #go and #stop neurons talk to each other and where exactly in the brain, then we could find new targets for Deep Brain Stimulation to make it work better.”

 

To follow Marie:  

Images were created on Biorender

Meet Jami Jackson Mulgrave, Postdoctoral Fellow in Biomedical Informatics

Dr. Jami Jackson Mulgrave, Postdoctoral Research Fellow in Biomedical Informatics at Columbia University

Meet Our Postdocs: Jami Jackson Mulgrave, Postdoctoral Research Fellow in Biomedical Informatics at Columbia University


Which department are you in at Columbia and what is your position?

I am a National Library of Medicine Postdoctoral Fellow in the Biomedical Informatics Department.

Where are you from and how long have you been in NYC?           

I am from Durham, NC. I graduated from Columbia University with a BA in psychology in 2007 and lived in NYC until 2012. I went to graduate school in NC from 2012 and moved back to NY in 2017.

Where did you go to school? Describe your path to your current position.          

I went to North Carolina State University for my MA and PhD in Statistics on a NSF graduate research fellowship. My graduate research involved using Bayesian methods to learn semiparametric graphical models.  I went to Columbia University for my BA in Psychology. I originally wanted to become a medical doctor, so I worked at Memorial Sloan-Kettering Cancer Center in clinical research for 5 years after graduating with my bachelor’s degree. I ultimately decided medical school wasn’t for me and I was more interested in statistics, machine learning, and data science.

What research question are you trying to figure out right now?

My work involves using data assimilation to estimate parameters related to Type 2 diabetes.

In a nutshell, what tools or approaches are you using to try and figure this out?

My main question is whether we can estimate parameters of a model of glucose and insulin dynamics to study differences in parameter patterns between patients with type 2 diabetes and patients without type 2 diabetes using the lab results of oral glucose tolerance tests found in an electronic health record.

We are using data assimilation tools to do the estimation.

What is the best part of your job?            

Working on a problem that has the potential to make an impact on patients in the future.

Why do you love science?

I love science because I love discovery and creativity. We don’t know what answer we are going to get and we can be creative about how we get to the answer.

What advice would you give to people interested in a career in science?

Follow what interests you and your passions. Don’t go into a science you think others would want you to be in, follow the science you love.

Tell us a bit about yourself or your projects that are not related to science.           

I am also a singer and songwriter.

What is your favorite thing about NYC?

The food!

When did you join CUPS and what is your current role, if any?        

I joined CUPS in 2018 and I am currently a liaison with the URPostdocs group.

URPostdocs is the Underrepresented Postdocs group at Columbia seeking to unite underrepresented postdocs (Women, Latinos, African-Americans, Native Americans, persons with disabilities, etc) into one group. The group is committed to advocate and find means to improve recruitment, retention, and mentoring of URPostdocs to aid in the development of successful careers both in academia and non-academic settings.

What do you like the most about CUPS? 

I like that it is led by passionate postdocs who want to make the postdoctoral experience better for all of us.

To follow Jami:

   

 

 

 

Careers Beyond the Postdoc

Careers Beyond the Postdoc:

May 31st, 2019 @ Alumni Auditorium, CUMC Campus (Organizers: Upasana Roy, Aditi Falnikar & Alex Karambelas, Research & Professional Development Committee) 


One of our CUPS flagship events, Careers Beyond the Postdoc, happened last Friday in the beautiful Alumni Auditorium. A full house with over 60 attendants and 25 speakers.

  

Careers Beyond the Postdoc‘ mission is to help connect current postdocs with future non-academic careers, including (among others): data science, regulatory affairs, medical writing, editing, scientific consulting, science outreach, biotech, tech transfer, and many more!

 

We invited 25 professionals to talk about their role and responsibilities and how they navigated their career path post-PhD. Held every two years, the event is always a huge success, bringing in a wide variety of professionals and interested postdocs across all Columbia campuses.

 

 

Warm thank you to all our speakers for sharing their experience with our postdocs!

Judith Absalon, Pfizer – Senior Medical Director

Yana Zorina, Acorda Therapeutics – Scientist-I

Corentin Moevus, C16 Biosciences – Scientist

Anil Vaidya, Pfizer – Director of Regulatory Affairs

Hui Wang, Regeneron – Manager, Regulatory Affairs

Chiara Bertipaglia, Zuckerman Institute – Scientific Program Manager

Joan Martinez, Columbia Technology Ventures – Technology Licensing Officer

Ananda Ghosh, NYU – Business Development Professional

Shachi Bhatt, Rockefeller Press – Scientific Editor

Alejandro Montenegro-Montero, Health Science Reports – Scientific Editor

Michelle Benson, Columbia University – Assistant Director for Research Integrity and Compliance

Shenell D. Evans, The Floating Hospital – Adjunct Professor of Clinical Psychology

Banke Fagbemi, New York Genome Center – Director of Business Development

Deb Aronson, Grey Health Group – VP, Medical Director

Ross Fadely, Insight Data Science – Data Scientist

Ken McCallum, Uncommon Goods – Data Scientist

Odaelys Walwyn, RockEdu – Scientist/Educator

Alfred Adomako, Lockwood Medical Communications Group – Associate Scientific Director

Christopher Aston, Columbia University EH&S – Associate Director

Peter Caracappa, Columbia University RSP – Chief Radiation Safety Officer

Daniel Lewis, Cello Health BioConsulting – Consultant

Malcolm Nason, BonBouton – VP R&D


For questions about this event or similar future events, please contact us: cups_executive@columbia.edu

Social Media for Academics

Social Media for Academics:

May 23rd, 2019, 6-8pm @ Fairchild, Morningside Campus (Organizer: Micaela Cunha & Alex Karambelas, Research & Professional Development Committee) 


Wondering about how to best use your digital presence to advance your career? You are not alone! Managing your activity in digital platforms such as LinkedIn, Twitter, ResearchGate, or others, can be daunting! 

 

   

 

This is why we hosted a Q&A panel with active social media users with an academic background, Mariam Aly and Alejandro de la Puente, to discuss different perspectives on how to leverage your online presence for your professional growth. 

 

Tips we learned:

– social media is great to grow your network

cultivate connections, build relationships

quantity vs. quality

choose who to follow, prioritize, establish rules not to be overwhelmed

– do it because you like it, it’s not essential


Our speakers:

Mariam Aly  

Mariam Aly is an Assistant Professor in Psychology at Columbia University. She is passionate about science outreach and communication, and the importance of happy and healthy lab environments.

She uses Twitter in two main ways: 1) one aimed at science communication and career advancement — sharing and discussing papers, broadening her scientific network, and discussing controversial topics in her field. 2) Her other goal in using Twitter is to expose the human side of science by talking about imposter syndrome, mental health struggles, and the ups and downs of academia.

 

Alejandro de la Puente  

Alejandro de la Puente is the Associate Director of the Science Alliance at the New York Academy of Sciences (NYAS). He received his PhD in theoretical physics. At NYAS, his goal is to provide all Science Alliance members with professional development programs and opportunities to help them grow their careers. Alejandro’s passion and mission is to help young STEM students and professionals achieve their full potential while increasing diversity and inclusivity in the STEM ecosystem in the U.S. and the wider world.

Spring Yankees outing

Spring Yankees outing:

May 18th, 2019 @ Yankee Stadium (Organizer: Holly Hunsberger, Networking & Community Building Committee) 


Couple weeks ago a bunch of us ventured to the other side of the river — direction Yankee Stadium for a game against Tampa Bay. 

https://www.mlb.com/yankees

Beautiful spring day for a baseball game. The pinstripe pass tickets allowed us to view the game from multiple terrace areas while enjoying a free beer.

Great atmosphere and good chance for people to get outside and out of the lab!

 

CUPS/OPA Annual Ski trip

CUPS/OPA Annual Ski trip:

February 10th, 2019 @ Hunter Mountain (Organizers: OPA & CUPS) 


We’re catching up and talking a little about some of our earlier events this year, before this blog was born (born May 2019).

One of the big events earlier this year was the Annual Postdoc Ski Trip !

In February, Ben (VP of CUPS at Morningside) and other postdocs went to Hunter Mountain in upstate New York for skiing and snowboarding!

There was beautiful weather and plenty of snow. Everyone got to “chill” (yep..:)) during lunch and discuss science on the lifts.

Looking forward to going again next year!

CUPS 2019 first Art outing – Whitney Museum

CUPS very first Art outing – Whitney Museum:

May 24th, 2019 @ Whitney Museum (Organizer: Dhru Deb, Networking & Community Building Committee) 


A couple weeks ago, CUPS launched “CUPS HEART“, a series of CUPS-organized visits for postdocs to the most distinguished art museums and galleries in New York City!

whitney.org

A few of us headed downtown to Chelsea to the iconic Whitney Museum. On Friday nights they have a great “Pay as you wish” deal from 7pm-9:30pm.

There were many interesting exhibitions, the coolest one was called “Spilling Over: Painting Color in the 1960s” – which was a collection of paintings from the 60s that used bold & intense colors to activate perception and articulate new questions “specifically its relation to race, gender, and the coding of space.”

Work by Emma Amos, whitney.org

We also got to enjoy the stunning views of Hudson river and High Line from the open terrace!

Stay tuned for more CUPS art events this year! – Contact Dhru for any questions or suggestions.