Mechanism Underlying Attentiveness and Alertness Identified

Researchers 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 shows neurons with markers that enable optical stimulation (left) and recording (right).

Neurons with markers that enable optical stimulation (left) and recording (right). Image credit: Sur Lab.

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.

About this neuroscience research

Funding: This work is supported by the National Institutes of Health, the National Science Foundation, and the Simons Foundation.

Source: Picower Institute for Learning and Memory/MIT
Image Source: Image credited to Sur Lab
Original Research: Abstract for “An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity” by Naiyan Chen, Hiroki Sugihara and Mriganka Sur in Nature Neuroscience. Published online April 27 2015 doi:10.1038/nn.4002


Abstract

An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity

Cholinergic modulation of cortex powerfully influences information processing and brain states, causing robust desynchronization of local field potentials and strong decorrelation of responses between neurons. We found that intracortical cholinergic inputs to mouse visual cortex specifically and differentially drive a defined cortical microcircuit: they facilitate somatostatin-expressing (SOM) inhibitory neurons that in turn inhibit parvalbumin-expressing inhibitory neurons and pyramidal neurons. Selective optogenetic inhibition of SOM responses blocked desynchronization and decorrelation, demonstrating that direct cholinergic activation of SOM neurons is necessary for this phenomenon. Optogenetic inhibition of vasoactive intestinal peptide-expressing neurons did not block desynchronization, despite these neurons being activated at high levels of cholinergic drive. Direct optogenetic SOM activation, independent of cholinergic modulation, was sufficient to induce desynchronization. Together, these findings demonstrate a mechanistic basis for temporal structure in cortical populations and the crucial role of neuromodulatory drive in specific inhibitory-excitatory circuits in actively shaping the dynamics of neuronal activity.

“An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity” by Naiyan Chen, Hiroki Sugihara and Mriganka Sur in Nature Neuroscience. Published online April 27 2015 doi:/10.1038/nn.4002

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