2025 Hughlings Jackson Lecture: The Basal Ganglia and the Motivation to Act
Established in 1935, the Hughlings Jackson Lecture is The Neuro’s premier scientific lecture. It honours the legacy of British neurologist John Hughlings Jackson (1835-1911) who pioneered the development of neurology as a medical specialty. A reception will follow.
To register: coming soon
To view virtually: https://vimeo.com/event/5008767
Talk: The Basal Ganglia and the Motivation to Act
Speaker: Ann Graybiel, PhD
Institute Professor, Department of Brain and Cognitive Sciences, MIT
Abstract: It is universally recognized that the basal ganglia are implicated in major hypokinetic and hyperkinetic extrapyramidal motor disorders. But a shift in thinking about the basal ganglia is occurring with the realization that their reach extends beyond the control of movement to modulation of mood and cognition. In this lecture, I will focus on experimental work that favors these non-classical views and introduce evidence that previously unrecognized links between the striatum and the dopamine-containing neurons of the substantia nigra may be crucial to these non-classical functions of the basal ganglia. Foundational work has shown that a balance between two great basal ganglia output pathways, the Direct-D1 and Indirect-D2 pathways, is necessary for normal movement. Imbalance favoring the canonical D-1 ‘Go’ pathway is seen in hyperkinetic disorders including Huntington’s disorder, and imbalance favoring the canonical D-2 ‘NoGo’ pathway leads to hypokinetic disorders including Parkinson’s disease. Thus operationally, an agonist-antagonist balance is thought to regulate and coordinate movements, along with additional cooperative links between these. These pathways lead to the motor output nuclei of the basal ganglia. Quite outside this model is the nigro-striato-nigral loop, which is a target of Parkinson’s disease and has been implicated in a range of neuropsychiatric disorders. With the explosion of new methods in experimental neuroscience it now has been possible to catch the first glimpses of how these two circuit organizations could be aligned. Remarkably, it turns out that the canonical Direct and Indirect pathways are paralleled by a non-canonical pair of Direct and Indirect pathways that target not the motor outputs of the basal ganglia proper, but the dopamine-containing neurons of the substantia nigra. These newly recognized pathways arise from specialized, widely distributed modules in the striatum called striosomes, first identified in the human brain. Our evidence to date suggests that the striosomal pathways closely mimic the canonical pathways, except for their crucial differences in outputs targets. They seem to work in opposition to each other and have opposite Go-D1 NoGo-D2 polarities. These results are very new, but accumulating evidence already points to the striosomes as being functionally important for reinforcement-based learning, for behavioral engagement, for cost-benefit approach-avoidance decision-making, and for switching or maintaining mood and bodily states, all concordant with evidence that the striosomal circuits receive inputs from limbic system-related regions. Together, these findings can help to forge new models of basal ganglia function that include motivation and mood as parts of a network of forebrain control circuits interacting with dopamine and other neuromodulators to influence behavioral and cognitive action.
