They say that he human brain is the most complex machine in the universe, and it’s for good reason. Brains are comprised of about a hundred billion neurons that typically form a thousand unique connections each. As a result scientists estimate that the brain can store ten to a thousand times more information than modern day laptops.

computer-brain-interface-darpa-sHowever, what is even more impressive than the storage capacity of the brain is its ability to dynamically read and process massive amounts of information. Every second that you are awake, your brain is efficiently parsing through constantly flowing streams of visual, auditory, gustatory, and olfactory data. How does the brain sort through all this rich information? What mechanisms underlie our ability to prioritize important sensory information when presented with competing or conflicting cues?

These open questions in neuroscience have long puzzled scientists. In this post, we will take a look at the paper from Michael Halassa’s group, titled “Thalamic control of sensory selection in divided attention”,  that sheds some light on these questions. The central goal of the article is to provide some proof for the hypothesis that the frontal cortex, the home of executive function, regulates the selection of sensory information in the thalamus, the hub of sensory inputs into the brain.

To accomplish this, Halassa first creates a rodent psychometric test that basically tests the ability of a mouse to secure a food reward when presented with either congruent or conflicting visual and auditory stimuli.  As expected, mice were forced to divide their attention when presented with both visual and auditory information. When presented with conflicting auditory tones, mice had a higher visual detection threshold, which persisted even as the tones were switched back to being congruent. This provided evidence that top-down processing, likely from the frontal cortex was biasing the visual stream! Next the authors sought to pin down the circuit mechanisms of this finding.

Next using optogenetics, a technique to make neurons respond to light, Halassa’s group linked channelrhodopsin to GABAergic inhibitory cells in the frontal cortex. This allowed them to effectively silence activity between a region of the frontal cortex that sends projections to the thalamus, the sensory hub. In the same behavioral tests, the mice perform much worse when the link between the frontal cortex and the thalamus is inhibited. Without this connection, mice are suddenly unable to sort out conflicting sensory cues in order to complete the task!screen-shot-2017-03-06-at-1-30-21-am

Importantly, the paper also shows that a similar sort of disruption scheme in the visual cortex fails to disrupt task performance in a similar manner. This means that the cross-cortical interactions are less important than corticothalamic connections, which was previously not known.

In order to fully characterize the circuit, optogenetic methods were combined with viral tracing to follow the projections from the frontal cortex to a particular region in the thalamus, called the thalamic reticular nucleus (RTN). Using electrophysiology and optogenetics, it is shown the neurons in this region fire specifically when conflicting auditory tones are played, and that silencing this region results in the a similar hit in task performance, as above. Quite convincingly, it seems the the thalamic target of the frontal cortex for sensory selection is the RTN.

screen-shot-2017-03-06-at-1-49-58-am

To wrap this study up, the authors investigated the interaction between the RTN and adjacent lateral geniculate nucleus (LGN), a thalamic structure that is crucial for visual processing. Using a novel assay for in vivo inhibitory activity (FRET photometry), they demonstrate that when mice are attending to conflicting auditory cues, the RTN uses direct feed-forward inhibition, as measured by intracellular chloride ion shifts, on the LGN to alter visual perception.

In summary, this article elegantly describes the link between the frontal cortex, the thalamus, and the visual system using a plethora of high-powered and novel experimental techniques. The authors provide convincing evidence for a mechanism in which the more “intelligent” regions of the brain regulate the flow of sensory information such that cues relevant to the task at hand are amplified and useless cues are discarded.

To learn more about the work conducted in Dr. Halassa’s lab, please attend his talk this Tuesday, March 7th, at 4:00pm in the Center for Neural Circuits and Behavior.

Debha Amatya is a third year MD/PhD student in the Laboratory of Genetics at the Salk Institute. He’s interested in psychiatric genomics and weightlifting. 

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