Description:

The Department of Neuroscience Presents:

The James C. Houk Lecture in Motor Control: "Basal Ganglia and the Decision to Act"

Ann Graybiel, PhD
Institute Professor
McGovern Institute for Brain Research
Massachusetts Institute of Technology

Abstract
Every day is replete with occasions when ‘doing or not doing’, ‘going or not going’ decision-making is required. A wealth of evidence suggests that the basal ganglia underpin these daily behaviors. Yet a critical gap remains in understanding mechanisms underlying the modulation of motivated actions, both under normal conditions and in the wake of movement disorders. The basal ganglia are critical for this modulation. The canonical direct-D1 ‘Go’ and indirect-D2 ‘No-Go’ basal ganglia pathways are universally considered essential for these functions. Strong evidence and advanced models show that the direct-D1 and indirect-D2 pathway activities must be balanced for normal control. When they are out of balance, neurologic and neuropsychiatric disorders ensue, and pharmacologic and other treatments for Parkinson’s disease are largely based on these classical direct-indirect models of these circuits. Yet there is controversy about the degree to which the direct and indirect pathways act together or in opposition, as the classic models suggest. In our lab, we have found evidence strongly suggesting that extensions of these models are called for. By genetic engineering, we have delineated a pair of direct and indirect pathways that emerge from the striatum separately from the canonical pathways and that, unlike the classical pathways, target the dopamine-containing neurons of the substantia nigra pars compacta. They receive input from cortical areas related to the limbic system, in contrast to the sensorimotor inputs to the canonical direct and indirect pathways. This newly delineated parallel pathway architecture of the basal ganglia at once suggests the need for talking account of this dual system in clinical settings and suggests a model whereby evolution provided a way to have behavioral state modulate the coordination of movement control and motivated action.

About Dr. Graybiel
Ann M. Graybiel is an Institute Professor at the Massachusetts Institute of Technology, where she and her laboratory are actively investigating neural circuits related to the basal ganglia and to a range of neurologic and neuropsychiatric disorders. Her work is centered on understanding the functions of circuits leading from mood-related parts of the frontal neocortex through the striatum to the dopamine-containing neurons of the midbrain. This work took its origin in her discovery of neurochemically distinct compartments in the striatum, which she named ‘striosomes’. These are now known to provide all or nearly all striatal input to the dopamine-containing neurons of the midbrain. These circuits strongly bias decision-making made under motivationally challenging conditions, as though inducing optimistic or pessimistic state changes. They can strongly modulate responses to stress and levels of engagement across age, and levels of reinforcement-based learning. Her group is now harnessing molecular and genetic markers in functional work of these and related circuits of the striatal matrix, with the goal of contributing to clinical medicine as well as to fundamental understanding of the brain.

About the James C. Houk Lecture in Motor Control
In 2020, the late James C. Houk, PhD, and his wife Antoinette made a bequest to establish the Dr. James Houk Graduate Fellowship in Neuroscience. Their gift provides funding to outstanding graduate students studying neurophysiology at Northwestern and supports the annual James C. Houk Lecture in Motor Control, presented by a renowned motor neuroscientist.

About James C. Houk, PhD
Dr. James C. Houk originally studied electrical engineering before receiving his PhD in physiology at Harvard University. As an assistant professor at Harvard, he studied Golgi tendon organs, muscle spindles and developed control models of muscle activation through neuronal circuits in the spinal cord.

Later, as an associate professor at Johns Hopkins Medical School, Houk began work on the central nervous system in behaving monkeys, work he continued at Northwestern University, after being recruited in 1978 as chair of the Department of Physiology (now Neuroscience). During this time, Houk also built a world-renowned systems neuroscience group within the department.

In 2001, after 23 years, Houk stepped down as chair to concentrate on multimodal approaches to studying how the nonlinear dynamics of microscopic modules in the brain give rise to its unique computational properties. He became particularly interested in the interplay between the basal ganglia, motor cortex and cerebellum.