Mriganka Sur - Picower researchers ID brain mechanisms underlying alertness and attentiveness
First demonstration that a common neurotransmitter acts via a single neuron type to enable effective information-processing.
Picower Institute for Learning and Memory
April 27, 2015
at MIT’s Picower Institute for Learning and Memory have shown for the
first time that a common neurotransmitter acts via a
single type of neuron to enable the
brain to process information more effectively. The study appears in the April 27 advance online edition of Nature Neuroscience.
A fundamental feature of the awake, alert brain is the release of the
neurotransmitter acetylcholine (ACh). By zeroing in on a specific
cortical circuit driven by a single cell type, “this paper shows that a
crucial function of ACh is to enhance information representation by
acting principally on one class of inhibitory neuron in the cortex,”
says co-author Mriganka Sur, the Newton Professor of Neuroscience and
director of the MIT Simons Center for the Social Brain. “We have
pinpointed the mechanism underlying a fundamental aspect of information
representation in the brain.”
There are many scenarios in which being in sync is a good thing. The attentive brain, surprisingly, is not one of them.
Decorrelation — neurons firing in an unsynchronized manner — can
enhance and even optimize information processing. In fact, conditions
such as Parkinson’s disease and epilepsy are characterized by
pathologically synchronized neurons.
The Picower study pinpoints, for the first time, a specific subtype
of inhibitory neuron that contributes to decorrelation in a major brain
circuit tied to attention and arousal.
The mechanisms underlying ACh-modulated brain functions are complex
due to the sheer number of types of brain cells that ACh modulates, says
former MIT graduate student Naiyan Chen, co-author of the paper.
“Surprisingly, we found a single cell type is responsible for ACh-based
information representation in the brain.”
This study, intended to shed light on brain function at the circuit
level, is “the first to demonstrate a crucial emerging principle of
cortical circuits: that the diffuse release of ACh within the cortex,
previously thought to contribute to nonspecific actions, actually leads
to highly specific functions,” Sur explains. “Certain cells have
receptors that are finely tuned to such transmitters, and these cells
are in turn part of specific circuits.
“This enables neurotransmitter systems and cortical circuits to
create very specific response transformations that underlie cognitive
functions such as attention and brain states that accompany alertness
and arousal,” he says.
Naiyan and research scientist Hiroki Sugihara demonstrated these
circuits and their function in genetically modified mice by recording
the actions of specific neurons and activating and inactivating
different neuron classes to deconstruct their roles.
Chen anticipates that these findings will motivate future research in
other brain functions — such as learning and plasticity — modulated by
the neurotransmitter acetylcholine. “An interesting next question is: Do
different acetylcholine-modulated cell types mediate different brain
functions?” she says.
This work is supported by the National Institutes of Health, the National Science Foundation, and the Simons Foundation.