When Marco Polo made his famous journey to find a better route from Asia to Europe, his travels produced the Fra Mauro map, the 15th-century medieval view of how the known world was laid out. As you can see at left, it kind of resembles what we know now thanks to additional exploration of both the terrestrial and outer-space kind. But it’s still only a vague approximation, accurate in some parts (such as the boot of Italy) and malformed in others (what is going on with West Africa?).
Today, even with amazing advances in imaging that allow us to view ripples of activity as the brain works, science remains in the early stages of neural cartography, possessing only a rough draft of how the brain connects that will surely look primitive to future neurobiologists. The various structures of the brain have been known for decades, even centuries, thanks to surgical dissection. But how those brain regions interact and connect, and how those billions of connections add up to the amazing computational ability of the human brain, remains a monumental challenge.
That challenge comes to mind when reading two brand-new papers from the laboratory of Murray Sherman, professor and chair of neurobiology at the University of Chicago Medical Center and a specialist in the field of neuroanatomy. Much of Sherman’s research is dedicated to a brain region known as the thalamus, a structure located practically in the very center of the brain. What most students are taught about the thalamus is that it is a kind of sensory crossroads for the brain, passing along information from the visual, auditory and somatosensory (touch) systems to the relevant areas of cortex, where that information undergoes complex processing. But whether the thalamus merely makes sure the information gets to the right place and then shuts up, or whether it alters the information and stays a part of the conversation as it is processed, remains a subject of debate.
These two papers score points for the latter scenario, where the thalamus is a conductor of sensory information rather than a mere pit stop along the way to the cortex. In the first, published by Brian Theyel, Daniel Llano and Sherman in Nature Neuroscience yesterday, a novel imaging technique is used to prove that the thalamus continues to shuttle information between cortical areas even after the initial handoff. The second paper, published today in the Proceedings of the National Academy of Sciences by Charles Lee and Sherman, finds that the thalamus receives two different streams of auditory information, implying that its role is more complicated than mere conduit.
“These experiments not only give you a new way of looking at how cortex functions, but also answers a question about what most of the thalamus is doing,” Sherman said. “People who study how the cortex functions now have to take the thalamus into account. This can’t be ignored.”
The Nature Neuroscience paper creates a new map of how somatosensory information passes between cortical areas. Classically, sensory information is thought to travel from thalamus to primary cortex, then to secondary cortex, and so on, with the processing of that information growing more and more complex as it goes. But when Theyel applied an imaging technique called flavoprotein autofluorescence imaging (FA imaging, for short) to a mouse brain preparation that included both thalamus and somatosensory cortex, he saw information jumping back to the thalamus between primary and secondary cortex. The video below illustrates this pathway, called a corticothalamocortical loop – when you cut the connections between primary and secondary cortex, stimulating primary cortex still activates secondary cortex via a thalamic route (that’s the thalamus lighting up in the middle of the brain slice).
Why would sensory information travel “backwards” to the thalamus as it jumps between cortical regions? Sherman suggests that it’s good to keep the thalamus in the loop as the brain makes sense of the information its receiving – in one example, perhaps the thalamus keeps in touch with motor areas, so the brain can tell the difference between when an object moves and when it appears to be moving due to eye movements. Having the thalamus continuously involved may also play a role in attention, directing the brain’s processing to particular sights and sounds and blocking out others. In that scenario, the central location of the thalamus, and its crossroads role, puts it at an advantage.
“The thalamus is a remarkable bottleneck,” Sherman said. “But that may be because, as a bottleneck, it provides a very convenient way to control the flow of information. It is a very strategically organized structure.”
That strategic organization comes into play in Lee and Sherman’s PNAS paper (not online yet), where Lee (co-producer of the Groks science podcast site) did the laborious but necessary work of tracing what neurons project where in the auditory pathway. The inferior colliculus, another brain region involved in hearing, sends two projections to the thalamus, which some scientists have theorized is a sort of precautionary backup system – doubling the information so that one’s sense of hearing can survive losing one route.
But when Lee stimulated different parts of the inferior colliculus – and by extension, the two pathways to thalamus – he found very different responses. One pathway, originating in the central nucleus of the inferior colliculus, excited the thalamus, suggesting this was a straightforward “driver route” for auditory information. Stimulating the other pathway via the “shell” region of the inferior colliculus produced a less uniform response in thalamus, a mixture of excitatory and inhibitory responses. The second pathway then appears to be more of a “modulator” route, perhaps influencing the information seen bouncing back from cortical areas in Theyel’s experiments.
It all adds up to a redrawing of the brain’s map, in function if not in geography. The thalamus hasn’t moved, but rather than being a refueling station between continents, it’s now an O’Hare-like hub, a place where a whirlwind of incoming sensory information is organized and re-dispatched to its proper destination.
“The thalamus really hasn’t been a part of people’s thinking of how cortex functions,” Sherman said. “But the hope is these kinds of demonstrations will start putting the thalamus on the map.”