By Dirk Hoffman

Garrett Neske, PhD, assistant professor of physiology and biophysics, is principal investigator on the five-year, $2.18 million R01 grant from the National Eye Institute, part of the National Institutes of Health (NIH).

The title of the study is “Mechanisms of Higher-Order Thalamic Control Over Visual Cortical Processing.”

The cortex is the part of the brain most strongly associated with many of the most complex aspects of perceptual, motor, and cognitive abilities, Neske notes.

For the cortex to operate, it needs to constantly process and route information correctly, not only within individual cortical areas, but particularly between distant cortical areas, he adds.

“The goals of the current study are to explore a poorly understood yet potentially powerful mechanism of long-range cortical communication,” Neske says. “Specifically, we will study the detailed synaptic mechanisms by which a particular region of the thalamus, called the pulvinar, allows different visual cortical regions to communicate with one another to give rise to visual perception.”

Specific aims of the study are to:

• uncover the fundamental synaptic organization of corticocortical (CC) and transthalamic pathways linking functionally distinct visual cortical regions
• determine the state-dependence of information transmission through transthalamic pathways
• determine the distinct contributions of transthalamic and corticocortical pathways during perceptual decision making

Harnessing mouse models of visual processing, the researchers will be using a wide range of techniques (from synaptic physiology in brain slice preparations) to state-of-the-art neuronal recording techniques in awake, behaving animals to uncover not only the basic functional architecture of the pulvinar and its connected cortical areas, but also how this architecture gets engaged during different states of wakefulness and during behavioral tasks that require making decisions based on visual stimuli.

Given how important the functional connections between different regions of the cortex are for basic brain function, there are a host of both neurological and psychiatric diseases that can result when these connections don’t function properly, according to Neske.

“In visual processing, deficits such as spatial neglect and cerebral visual impairment can result if the proper routing of signals between visual cortical areas is compromised,” Neske says. “More broadly, disorders such as autism and schizophrenia are also due in large part to problems with cortical synaptic communication.”

Although the project falls within the domain of basic neuroscience, as the underlying mechanisms of the system under investigation remain incompletely understood, Neske says that elucidating these mechanisms may provide important insights into potential therapeutic approaches for conditions associated with disrupted information flow within the cortex.

Neske previously received a K99-R00 award, also from the National Eye Institute, which funded the last few years of his postdoctoral research and the first three years of his independent position at UB. The new grant marks the first R01 award he has received.

“Receiving the first R01 is a highly significant event for an early-stage investigator like me,” he says. “I'm very grateful that my peers on study section, NIH programming staff, and the scientists on the advisory council of the National Eye Institute thought so highly of my proposal. My lab and I are looking forward to carrying out the proposed work.”