Amy Arnsten, professor of neurobiology and a member of the Kavli Institute for Neuroscience at Yale, has received a 2013 Pioneer Award from the National Institutes of Health.
The award is designed to support “visionary investigators” pursuing highly creative biomedical research projects and is worth $2.5 million over 5 years. Arnsten is one of just twelve Pioneer Award-recipients this year under the funding agency’s High-Risk High-Reward program.
Arnsten is an expert in the neurobiological mechanisms underlying cognition, and the brain regions, called the association cortices, that support it. Her lab has discovered some of the molecular pathways that govern the function of the prefrontal association cortex, the seat of higher-order thinking in the brain.
“What Amy is doing is very unique and closely aligned with the one of Institute’s goals, to understand the neurobiology of thought,” says Pasko Rakic, director of the Kavli Institute. ”Few researchers study molecular influences in primates, yet this is an essential arena if we are to comprehend and treat disorders of higher cognition.”
In particular, Arnsten has found that the highly evolved neuronal circuits in the primate prefrontal association cortex are regulated differently than the sensory cortex, which processes information from our senses, and subcortical structures. Her lab has discovered molecular signaling pathways near synapses — the junctions between neurons — that dynamically alter synaptic strength, enhancing mental flexibility and coordinating cognitive and arousal states. For example, when an organism is exposed to stress, these signaling events disconnect prefrontal networks, switching control of behavior to more primitive brain circuits.
She has also shown that when these molecular events become unregulated, due to a genetic glitch or aging, the brain’s ability to store and manipulate thoughts is impaired. This impairment may underlie disorders such as schizophrenia and Alzheimer’s Disease.
Based on this work, a new medication, guanfacine (Intuniv™), is now in widespread use for the treatment of prefrontal cognitive disorders.
With the new grant, Arnsten aims to understand why the primate association cortices are so vulnerable compared with the evolutionarily older sensory cortices Understanding what predisposes the association cortices to dysfunction may help researchers to prevent the degeneration of higher cognitive circuits.
This new research builds directly on earlier work supported by the Kavli Institute, where she uncovered how ion channels — pores that control the flow of electrical current across the nerve cell membrane — near cortical synapses control prefrontal network connections.
Tamas Horvath, chair and professor of comparative medicine and a member of the Kavli Institute’s steering committee, also holds a Pioneer Award, which he received in 2010 to study the effects of metabolism on brain function.