Saturday, July 06, 2013

Randy Bruno - The Cerebral Cortex Is Wired with Two Separate Circuits that Do Separate Things

A new study out of Columbia University, by neuroscientist Randy Bruno, offers what the authors claim is a new model for how the brain is wired. In a study on rat brains, Bruno found that sensory stimuli are processed in two areas of the cortex simultaneously - what previously has been theorized as parallel processing (see Borst, Thompson, and Kosslyn, 2011, American Psychologist, who also proposed an upper and lower pathway in the cortex).
“The upper and lower layers form separate circuits that do separate things.” The discovery, he says, “opens up a different way of thinking about how the cerebral cortex does what it does, which includes not only processing sight, sound, and touch but higher functions such as speech, decision-making, and abstract thought.”
This is not a new idea - it has been assumed that the brain is capable of parallel processing for more than two decades (research looked at the parallel processing of pain in 1991). Here are a couple of older examples (from the Borst, Thompson, and Kosslyn article):
Wilson, Scalaidhe, and Goldman-Rakic (1993) showed that the ventral pathway projects to the ventrolateral prefrontal cortex, whereas the dorsal pathway projects to the dorsolateral prefrontal cortex, mediating, respectively, object working memory and spatial working memory.
And
Goodale and Milner (1992) proposed an alternative account of the functions carried out by the two cortical pathways. Within their framework, the dorsal pathway mediates the control of action by transforming spatial information about objects (locations and spatial configurations) to guide actions. In contrast, the ventral pathway identifies objects, actions, and causal relations between them (see also Milner & Goodale, 1995; Goodale, 2008). This characterization led Goodale and Milner to dub the dorsal and ventral pathways the how and what systems, respectively.
 Anyway, it's not a new idea, but it is another solid piece of the puzzle.

Study Advances New Theory of How the Brain Is Wired

A nerve cell in the thalamus (blue) sends its axon (red) into the cerebral cortex, where it makes synaptic connections with thousands of neurons. While most of these connections are in a middle layer of the cortex (gray rings), some sparse branches connect to deeper layers.

Speaking. Seeing. Hearing. Thinking. Remembering. Understanding this sentence and making a decision about whether or not to read on. All of this work is handled in the cerebral cortex, the deeply creased, outermost portion of the brain that is the center of all the higher brain functions that make us human. Humans have the thickest cortex of any species but, even so, it measures no more than 4 millimeters (.16 inches) thick.

For decades, scientists thought they had a pretty clear understanding of how signals move through the cerebral cortex. By studying the anatomy of nerve axons—the wires that connect nerve cells—they had concluded that information is relayed through a “column” of six layers of specialized nerve cells in a series of hand-offs that begins in the mid-layer of the cortex, then moves to other layers before triggering a behavioral response.

Now a study by Columbia neuroscientist Dr. Randy Bruno indicates this longstanding view is incorrect. Looking at how sensory information is processed in rats, Bruno found that signals are processed in two parts of the cortex simultaneously rather than in series—almost as if there are two brains.


Dr. Randy Bruno. Photo by Amelia Panico.

"Our findings challenge dogma,” says Bruno, assistant professor of neuroscience and a faculty member at Columbia’s new Mortimer B. Zuckerman Mind Brain Behavior Institute and the Kavli Institute for Brain Science. “The upper and lower layers form separate circuits that do separate things.” The discovery, he says, “opens up a different way of thinking about how the cerebral cortex does what it does, which includes not only processing sight, sound and touch but higher functions such as speech, decision-making and abstract thought.”

The study, co-authored with Christine Constantinople, who earned a Ph.D. at Columbia and is now a post-doctoral researcher at the Princeton Neuroscience Institute, appears in the June 28 edition of the journal Science.

The research was conducted in the well-understood sensory system of rat whiskers, which operate much like human fingers, providing tactile information about shape and texture. This information travels from nerve fibers at the base of the whiskers to the thalamus in the midbrain and then is processed in the cerebral cortex. Past research has mapped each whisker to a specific barrel-shaped cluster of neurons in the brain. “The wiring of these circuits is similar to those that process senses in other mammals, including humans,” Bruno notes.

The new study relies on a sensitive technique that allows researchers to record how signals move across synapses from one neuron to the next in a live animal by using micropipettes whose tips are just 1 micron wide—one-thousandth of a millimeter. The recordings showed that signals are relayed from the thalamus to the mid- and deeper layers of the cortex simultaneously with surprisingly robust signaling to the deeper layer.


A microscope image of a nerve cell and its many branches (or dendrites) 
in a deep layer of a rat's cerebral cortex.

To confirm that the deeper layer receives sensory information directly from the thalamus, the researchers blocked all signals from the mid-layer using a local anesthetic. Sure enough, activity in the deeper layer remained unchanged.

“This was very surprising,” says Constantinople. “We expected activity in the lower layers to be turned off or very much diminished.”

The study suggests that the upper and lower layers of the cerebral cortex form separate circuits that play separate roles in processing sensory information. Researchers believe that the deeper layers are evolutionarily older—they are found in reptiles, for example, while the upper and middle layers appear in more evolved species and are thickest in humans.

One possibility, suggests Bruno, is that basic sensory processing occurs in the lower layers: for example, visually tracking a tennis ball. Processing that involves integrating context or experience might be done in the upper layers – for example, watching where an opponent is hitting the ball and planning where to return the shot.

German neurobiologist Bert Sakmann, who won a 1991 Nobel Prize for developing the micropipette system of mapping nerve impulses, describes the study as a game changer. “Dr. Bruno has produced a technical masterpiece that now firmly establishes two separate input streams to the cortex,” he says.

Bruno’s lab is now focused on exploring how the various layers of cortex relate to specific behaviors, such as memory and learning. “Developing a more refined understanding of cortical processing will take the combined efforts of anatomists, cell and molecular biologists, and animal behaviorists,” says Dr. Thomas Jessell, Claire Tow Professor of Motor Neuron Disorders in Neuroscience and a director of both the Zuckerman Institute and the Kavli Institute. “The Zuckerman Institute, with its multidisciplinary faculty and broad mission, is ideally suited to building on Bruno’s fascinating new insight.”

—by Claudia Wallis
* * * * * * *

Here is the abstract from Science, which is not an open access journal.

DEEP CORTICAL LAYERS ARE ACTIVATED DIRECTLY BY THALAMUS


The thalamocortical (TC) projection to layer 4 (L4) is thought to be the main route by which sensory organs communicate with cortex. Sensory information is believed to then propagate through the cortical column along the L4→L2/3→L5/6 pathway. Here, we show that sensory-evoked responses of L5/6 neurons in rats derive instead from direct TC synapses. Many L5/6 neurons exhibited sensory-evoked postsynaptic potentials with the same latencies as L4. Paired in vivo recordings from L5/6 neurons and thalamic neurons revealed substantial convergence of direct TC synapses onto diverse types of infragranular neurons, particularly in L5B. Pharmacological inactivation of L4 had no effect on sensory-evoked synaptic input to L5/6 neurons. L4 is thus not an obligatory distribution hub for cortical activity, and thalamus activates two separate, independent “strata” of cortex in parallel.

Full Citation:
Constantinople, CM, and Bruno, RM. (2013, Jun 28). Deep Cortical Layers Are Activated Directly by Thalamus. Science: Vol. 340 no. 6140 pp. 1591-1594. DOI:10.1126/science.1236425
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