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November 2, 2015
Mapping brain circuits involved in attention
At a Glance
- Researchers have determined how a set of brain regions influences attention in mice.
- The findings suggest that problems with this neural circuit may lead to the concentration difficulties seen in numerous neurological conditions.
The brain receives lots of sensory information and must choose what to focus on and what to ignore. Many neurological disorders—including schizophrenia, autism, and attention deficit hyperactivity disorder—involve problems concentrating and ignoring distractions.
Scientists have long believed that a brain region called the prefrontal cortex (PFC) selects what information to focus on, but how this happens is unclear. Some have proposed that a brain region called the thalamus filters out irrelevant sensory inputs, while another common theory suggests that PFC neurons directly interact with the brain’s sensory cortical areas to modulate attention.
To investigate these ideas, a research team led by Dr. Michael Halassa of New York University used a light-based technique called optogenetics to activate and inhibit specific brain regions in mice. The work was partially funded by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH). The results were published in Nature on October 29, 2015.
The team trained mice to listen for distinctive tones that informed them whether to then pay attention to a light or a sound to figure out which of 2 ports hid a reward. The mice needed to use the right cue and ignore the irrelevant one in order to choose the correct door and get their reward. This is called a cross-modal task, as it relies on 2 senses.
The researchers found that when they optogenetically silenced neurons in the PFC before the cues were presented, the mice made more errors choosing the appropriate cue. These errors depended on the cross-modal nature of the task, as perturbing PFC activity in a visual-only version of the task had no effect on performance.
When the team silenced neurons in the visual cortex, which processes visual information, only visual performance of the cues was affected—and only at the time the cues were presented, not before as with the PFC. Similarly, silencing neurons in the auditory cortex only affected sound-related performance. Taken together, these findings challenge the notion that the PFC influences attention by directly affecting circuits in these sensory cortices.
The scientists next used similar techniques in the thalamus, which previous studies suggested plays a role in attention. Manipulating the activity of neurons in an area called the visual thalamic reticular nucleus (visTRN) either before or during cue presentation increased errors, suggesting that the PFC interacts with the sensory thalamus to shift attentional focus. The team found that when the mice needed to focus on the light, activity dropped in the visTRN and rose in another part of the thalamus that processes visual information, the lateral geniculate nucleus (LGN). But this didn’t happen when the PFC was inactivated, implying that the PFC modifies activity in areas of the thalamus in order to shift attention toward visual information.
Finally, the researchers developed a technique to directly measure nerve cell inhibition. They found that LGN neurons were inhibited more when the mice had to concentrate on the sound. However, this effect wasn’t seen when the visTRN was silenced. These results suggest that the visTRN inhibits the LGN when a mouse needs to focus on sound.
“Our latest research findings support a newly emerging model of how the brain focuses attention on a particular task, using neurons in the thalamic reticular nucleus as a switchboard to control the amount of information the brain receives, limiting and filtering out sensory information that we don’t want to pay attention to,” Halassa says.
Future studies will explore the activity of these circuits in neurological disorders.
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References: Thalamic control of sensory selection in divided attention. Wimmer RD, Schmitt LI, Davidson TJ, Nakajima M, Deisseroth K, Halassa MA. Nature. 2015 Oct 29;526(7575):705-9. doi: 10.1038/nature15398. Epub 2015 Oct 21. PMID: 26503050.
Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH); Swiss National Science Foundation; Simons Foundation; Sloan Foundation; Brain and Behavior Research Foundation; Feldstein Medical Foundation; and a Klingenstein-Simons Fellowship.