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Biophysics, Dendrites & Neural Computation

 

We seek to understand how the biophysical features of neurons give rise to the computational power of the brain.

Our laboratory is located in the McGovern Institute for brain research and the department of brain and Cognitive Sciences at MIT in Cambridge, MA.

 

 

 

 

HARNETT LAB @ MIT

 

We have three main directions of research, each centered around dendritic processing:

 

Dendrites & computation

Our laboratory studies how the biophysical features of neurons, including ion channels, receptors, and membrane electrical properties, endow neural circuits with powerful processing capabilities, ultimately allowing them to perform the complex computations required to drive adaptive behavior.  We focus on the role of dendrites, the elaborate tree-like structures where neurons receive the vast majority of afferent input.  Due to the spatial arrangement of synaptic contacts on dendrites and the presence of particular biophysical mechanisms a complex array of interactions among synapses can take place.  Elementary input-output operations that manifest as coincidence detection, pattern recognition, input comparison, and simple logical functions can all be carried out even in small dendritic subunits.  Our hypothesis is that computations in neural circuits are built out of these fundamental integrative operations conducted at dendrites. The goal is to provide mechanistic explanations for how the neural circuits underlying sensory processing and navigation create complex, abstract representations of the environment and past experiences to ultimately guide behavior.

 

plasticity

If neural circuits use integrative operations at single neurons as the building blocks for computations, then synaptic and cellular plasticity provide a potent means for either reinforcing or changing neural processing algorithms.  Dendritic mechanisms governing input transformations likely impose plasticity induction rules distinct from the canonical spike-timing dependent plasticity framework, which currently dominates learning models.  Using electrical and optical recording in behaving rodents as well as in vitro preparations we hope to understand the mechanisms and functional consequences of plasticity in dendrites to ultimately relate changes in synaptic and cellular function to the alterations in computations that occur during learning to modify behavior.

 

Disorders of Cognition

Many cognitive disorders, including Autism, are characterized by conspicuous changes in the number, distribution, and/or morphology of dendritic spines, the anatomical locus of the majority of excitatory synapses in the brain. However, there is limited functional data on how, or even if, these morphological changes effect neural circuit operation.  We plan to address the relationship between anatomical aberrations observed in mouse models and the functional consequences for synaptic efficacy, plasticity, and integration to identify disease-associated mechanistic loci.  Manipulation of these processes during behavior is hoped to causally link changes in synapse anatomy and cellular function with potentially ectopic computations in the relevant microcircuit and behavioral alterations in these animals. We hope this novel research plan will shed new light on these complicated and currently intractable disorders.

 
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HARNETT LAB @ MIT

 

Publications

Harnett MT, Magee JC, Williams SR (2015) Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons. Journal of Neuroscience 35(3):1024-37

Harnett MT, Xu N, Magee JC, Williams SR (2013) Potassium channels control the interaction between active dendritic integration compartments in layer 5 cortical pyramidal neurons. Neuron 79(3):516-29                                                                                   *Preview article in Neuron by Dax Hoffman, p409

Marvin JS, Borghuis BG, Tian L, Cichon J, Harnett MT, Akerboom J, Gordus A, Renninger SL, Chen T, Bargmann CI, Orger MB, Schreiter ER, Demb JB, Gan W, Hires SA, Looger LL (2013) An optimized fluorescent probe for visualizing glutamate neurotransmission. Nature Methods 10(2):162-70

Xu N, Harnett MT, Williams SR, Huber D, O’Connor, DH, Svoboda K, Magee JC (2012) Nonlinear dendritic integration of sensory and motor input produces an object localization signal. Nature 492(7428):247-51

Harnett MT*, Makara J*, Kath W, Spruston N, Magee JC (2012) Synaptic amplification by dendritic spines enhances input cooperativity. Nature 491(7425):599-602

 
 
 

HARNETT LAB NEWS

 

July 3, 2017 - lab lunch on the green

Summertime is best time.

Summertime is best time.

Its all fun and games...

Its all fun and games...

...until someone tries to take Mateo's pizza.

...until someone tries to take Mateo's pizza.

 

June 29, 2017 - Andrew's end of rotation lunch

 

June 28, 2017 - Harnett lab retreat at Mark's house

 

June 5, 2017 - McGovern retreat in Providence, RI

Dad used to frequent The Black Pearl when he was stationed here back in the Navy.

Dad used to frequent The Black Pearl when he was stationed here back in the Navy.

So we all went for a drink!

So we all went for a drink!

 
"Hey Quique, is that really your fourth lobster?"

"Hey Quique, is that really your fourth lobster?"

"..."

"..."

"You are like a little baby.  Watch this."

"You are like a little baby.  Watch this."

 

May 12, 2017 - old Friends from janelia Ben sivyer and Greg gauvain visit the lab

 

They immediately begin reenacting some sort of human resources role-play thing in my office.  I think Ben just fired Greg...

 

April 28, 2017 - Mark teaches at ACAN on North Stradbroke Island in Queensland, Australia

Taxi, BOS->LAX->QLD, another taxi...

Taxi, BOS->LAX->QLD, another taxi...

 
On the ocean side of the island with ACAN course director Stephen Williams and my old Magee labmates Jinny Kim and Sebastian Royer.

On the ocean side of the island with ACAN course director Stephen Williams and my old Magee labmates Jinny Kim and Sebastian Royer.

Stephen and I explored the bay at low tide.

Stephen and I explored the bay at low tide.

...then a ferry out to the island from Brisbane...

...then a ferry out to the island from Brisbane...

...a quick pitstop at the Fruit Barn for caffeine...

...a quick pitstop at the Fruit Barn for caffeine...

...and right into a kayak...

...and right into a kayak...

This beach goes on for like 17 miles.

This beach goes on for like 17 miles.

This is literally across the street from the lab.

This is literally across the street from the lab.

with Maarten Kole!  Best way to avoid jetlag.

with Maarten Kole!  Best way to avoid jetlag.

We didn't see any whales or dolphins or sharks...

We didn't see any whales or dolphins or sharks...

Gorgeous sunsets here.

Gorgeous sunsets here.

ACAN was absolutely amazing.  I highly recommend it for those interested in learning rigorous patch-clamp electrophysiology:

http://acan.qbi.uq.edu.au/

 

April 20, 2017 - Marie wins the Walle Nauta Award for Excellence in Graduate Teaching.

Congratulations Marie!

Congratulations Marie!

 

april 16, 2017 - lou seriously wore a shirt with his z-stacks on it for his lab meeting

This is amazing.

This is amazing.

Lukas thinks so too.

Lukas thinks so too.

 

april 13, 2017 - Lukas and Jakob borrow Mark's car to pick up supplies at the hardware store.

With expressions like that, how could I not trust them?

With expressions like that, how could I not trust them?

 

march 25, 2017 - mark and lou attend the Dendrites gordon research conference in Tuscany

But first a quick stop with Elly Nedivi in Firenze for:

But first a quick stop with Elly Nedivi in Firenze for:

Gelato and ...

Gelato and ...

to say hi to the Boar!

to say hi to the Boar!

 
The view from the hotel.

The view from the hotel.

The hotel itself.

The hotel itself.

On a hike above the hotel.

On a hike above the hotel.

On a stroll through Castelnuovo di Garfagnana after lunch.

On a stroll through Castelnuovo di Garfagnana after lunch.

Mark and Lou out and about.

Mark and Lou out and about.

Mark with Nelson Spruston, Roberto Araya, and Kurt Haas at Guiseppe's in Barga.

Mark with Nelson Spruston, Roberto Araya, and Kurt Haas at Guiseppe's in Barga.

February 6, 2017 - donuts and dendrites lab meeting

Union Square donuts!

Union Square donuts!

And more dendritic patching than the audience can handle...

And more dendritic patching than the audience can handle...

 

February 2, 2017 - Jakob and Lukas setting up a high tech dissecting scope stand

Stability is obviously not a priority at this point...

Stability is obviously not a priority at this point...

 

January 17, 2017 - our first human slices

Mateo patches our first human neuron.

Mateo patches our first human neuron.

And is overjoyed about it.

And is overjoyed about it.

Pretty sweet...

Pretty sweet...

The lab is rapt as Lou patches human dendrites...

The lab is rapt as Lou patches human dendrites...

Quick break for food so we can patch through the night...

Quick break for food so we can patch through the night...

January 5, 2017 - Mateo has named the quad patch amplifiers

Its almost a full blown party!

Its almost a full blown party!

 

HARNETT LAB POSITIONS

 

Graduate students

We are currently accepting graduate students for rotations.  Please contact Mark directly.

 

 

 

 

HARNETT LAB CONTACT INFORMATION

McGovern Institute for Brain Research &        Department of Brain and Cognitive Sciences

MIT Bldg 46-6143
43 Vassar St
Cambridge, MA 02139

harnett@mit.edu

617.324.6989

 
 
 

 

 

 

 

© 2015 Mark Harnett.  All rights reserved