ICLM Journal Club
This Week - 31 January 2020 (9:30 a.m., Gonda 2nd Floor Conference Room)
Speaker: Marc Fuccillo
Title: “Circuit and Molecular Mediators of Goal-Directed Function”
Abstract: The organization of animal behavior according to goals is a key determinant of overall fitness and an amalgamation of interrelated behavioral processes - attention to relevant environmental cues, outcome-based choice reinforcement and avoidance, as well as invigoration of motor performance. Disruption in any of these processes can produce goal-directed dysfunction, a key behavioral endophenotype observed across neuropsychiatric disorders. Here, we examine the function of striatal circuits in mediating two aspects of goal-directed action – learning of a rewarded motor sequence and the selection of actions according to value.
For early motor learning, our lab has recently identified a crucial striatal cell type that modulates instrumental acquisition. In-vivo calcium imaging of the low-threshold spiking (LTS) interneuron subtype revealed a reward-associated activity that decreases as animals acquire an operant task. Further experiments demonstrated this striatal cell type can bi-directionally modulate early goal-directed instrumental learning. Current work exploring the mechanistic underpinnings of these effects will be discussed.
In separate experiments, our lab has examined how mutations in Neurexin1a, a synaptic adhesion molecule widely implicated in brain disease, contribute to alterations in value-based decision-making. Via circuit-specific genetic loss-of-function and reinforcement learning models, we find that inefficient choice patterns of Neurexin1a mutants result from deficiencies in updating and representation of value. Furthermore, this phenotype can be recapitulated with targeted Neurexin1a disruption in forebrain excitatory projection neurons. Finally, we demonstrate that these forebrain-specific mutants have loss of value-related neural signals within striatum.
The Integrative Center for Learning and Memory (ICLM) is a multidisciplinary center of UCLA labs devoted to understanding the neural basis of learning and memory and its disorders. This will require a unified approach across different levels of analysis, including;
1. Elucidating the molecular cellular and systems mechanisms that allow neurons and synapses to undergo the long-term changes that ultimately correspond to 'neural memories'.
2. Understanding how functional dynamics and computations emerge from complex circuits of neurons, and how plasticity governs these processes.
3. Describing the neural systems in which different forms of learning and memory take place, and how these systems interact to ultimately generate behavior and cognition.
History of ICLM
The Integrative Center for Learning and Memory formally LMP started in its current form in 1998, and has served as a platform for many interactions and collaborations within UCLA. A key event organized by the group is the weekly ICLM Journal Club. For more than 10 years, graduate students, postdocs, principal investigators, and invited speakers have presented on topics ranging from the molecular mechanisms of synaptic plasticity, through computational models of learning, to behavior and cognition. Dean Buonomano oversees the ICLM journal club with help of student/post doctoral organizers. For other events organized by ICLM go to http://www.iclm.ucla.edu/Events.html.
Current Faculty Advisor:
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