Where the nonspecific thalamus meets the prefrontal cortex: First measurements made of key brain links

December 4, 2012, Brown University

Inside the brains of mice and men alike, a relatively big football-shaped region called the thalamus acts like a switchboard, providing the prefrontal cortex, the part that does abstract thinking and decision-making, with most of its information. The thalamus's responsibility even includes helping the prefrontal cortex to maintain consciousness and arousal.

Essential as this "thalamocortical" partnership is, neuroscientists have understood very little about the connections coming from a matrix of cells in the so-called "nonspecific thalamus," where information other than from the senses is relayed. In a new paper published Dec. 5, 2012, in the , Brown University researchers report the first direct measurements in mice of cause-and-effect responses between the key thalamus cells in that matrix and those in the .

"These thalamic areas comprise the vast majority of the thalamus, but we know virtually nothing about the physiology of how they control [the] ," said one of the lead authors, Scott Cruikshank, assistant professor (research) of neuroscience at Brown.

Among the team's findings is that the nonspecific thalamus signals are most strongly received, at least at first, by inhibitory neurons in the outermost layer of cortex (layer 1). Neuroscientists had assumed that these signals instead mainly poured into excitatory cells of the cortex. It is only over time, with repetition of the thalamic signals, that the inhibitory layer 1 cells respond less strongly while the excitatory cells maintain a steady response. The result is a pattern in which the net effect of the thalamus signals is inhibitory in the cortex at first, but eventually gives way to a steadier, more even state of over a few hundred .

That ultimately sustained pattern of activation stands in stark contrast to the way the from the specific thalamus play out in the cortex. The resulting excitation in those circuits starts out strong and then weakens with repetition—consistent with how people cease to notice sights, smells, and other sensory inputs after a while if they don't change.

A large part of the reason why neuroscientists didn't know this before is because the measurements that Cruikshank and his co-authors made were difficult, if not impossible, to perform using traditional electrical stimulation and recording techniques. Once mouse tissue is sliced up, the long connections that the thalamus sends to the cortex, called axons, are severed. Electrically stimulating the axons where they connect to cortex cells, but nothing else around them, was impossible to do.

A relatively new technique called optogenetics made their measurements possible. Optogenetics allows scientists to genetically engineer specific types of neurons so that their activity can be controlled by different colors of light. The team, including co-lead author Omar Ahmed and senior author Barry Connors, chair of neuroscience at Brown, optogenetically engineered the thalamic matrix cells so that their severed axons could be selectively stimulated with light. Because other nearby cell types had not been optogenetically engineered, the light didn't stimulate them, too.

Meanwhile the researchers recorded the electrical activity of the various cortical cells the thalamic axons connected to, to see how they responded to stimulation of the thalamic axons. Sometimes the researchers recorded just the layer 1 , sometimes they recorded just the deeper-layered excitatory neurons and sometimes they recorded the different neurons' responses simultaneously. Notably, the outer-layer and deeper-layer cortical neurons are connected to each other as well.

The key results were measurements showing that the inhibitory outer-layer neurons, known as "layer 1 interneurons," have a roughly three-times stronger initial response to the thalamic signals than the deeper excitatory "pyramidal" neurons did. The responses eventually evened out, leading to that steady-state excitement over time.

Cruikshank said the team does not yet know what the behavioral significance of that steady state is, but it could be related to the maintenance of a baseline of or attention, perhaps to keep the prefrontal cortex ready to accept and process information from other sources, such as sensory signals. Prior experiments have shown that when the nonspecific thalamus is damaged, subjects can fall into a coma, but that when the nonspecific is stimulated the cortex becomes more aroused.

Now, at least, neuroscientists know how that connection is being made.

Explore further: Confirmation of repeated patterns of neurons indicates stereotypical organization throughout brain's cerebral cortex

Related Stories

Confirmation of repeated patterns of neurons indicates stereotypical organization throughout brain's cerebral cortex

May 11, 2012
Neurons are arranged in periodic patterns that repeat over large distances in two areas of the cerebral cortex, suggesting that the entire cerebral cortex has a stereotyped organization, reports a team of researchers led ...

Rewired visual input to sound-processing part of the brain leads to compromised hearing

August 22, 2012
Scientists at Georgia State University have found that the ability to hear is lessened when, as a result of injury, a region of the brain responsible for processing sounds receives both visual and auditory inputs.

Two heads are better than one: Gene expression reveals molecular mechanisms underlying evolution of cerebral cortex

November 9, 2012
Dramatic expansion of the human cerebral cortex, over the course of evolution, accommodated new areas for specialized cognitive function, including language. Understanding the genetic mechanisms underlying these changes, ...

Rats' stroke-induced seizures stopped with pulse of light

November 8, 2012
(Medical Xpress)—Stanford University School of Medicine scientists have shown that a structure deep within the brain is a crucial component of recurring seizures that can arise as a delayed consequence of a cerebral stroke. ...

Researchers identify possible trigger point of epileptic seizures

August 22, 2011
Researchers at the Stanford University School of Medicine have identified a brain-circuit defect that triggers absence seizures, the most common form of childhood epilepsy.

Recommended for you

Brain zaps may help curb tics of Tourette syndrome

January 16, 2018
Electric zaps can help rewire the brains of Tourette syndrome patients, effectively reducing their uncontrollable vocal and motor tics, a new study shows.

A 'touching sight': How babies' brains process touch builds foundations for learning

January 16, 2018
Touch is the first of the five senses to develop, yet scientists know far less about the baby's brain response to touch than to, say, the sight of mom's face, or the sound of her voice.

Researchers identify protein involved in cocaine addiction

January 16, 2018
Mount Sinai researchers have identified a protein produced by the immune system—granulocyte-colony stimulating factor (G-CSF)—that could be responsible for the development of cocaine addiction.

Neuroscientists suggest a model for how we gain volitional control of what we hold in our minds

January 16, 2018
Working memory is a sort of "mental sketchpad" that allows you to accomplish everyday tasks such as calling in your hungry family's takeout order and finding the bathroom you were just told "will be the third door on the ...

Brain imaging predicts language learning in deaf children

January 15, 2018
In a new international collaborative study between The Chinese University of Hong Kong and Ann & Robert H. Lurie Children's Hospital of Chicago, researchers created a machine learning algorithm that uses brain scans to predict ...

Preterm babies may suffer setbacks in auditory brain development, speech

January 15, 2018
Preterm babies born early in the third trimester of pregnancy are likely to experience delays in the development of the auditory cortex, a brain region essential to hearing and understanding sound, a new study reveals. Such ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

kochevnik
not rated yet Dec 04, 2012
Karl Pribram discussed this function of the thalamus in his book "Languages of the Brain" in the 70s. I've never assumed any other model because the effects would be counter to observation.

These guys need a computer to tell them hos stuff works. Connecting the dots isn't a valued skill in America, it would seem.

"You can always count on Americans to do the right thing… after they have tried everything else." - Winston Churchill

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.