ICLM Journal Club
This Friday - February 24, 2023 (9:30 a.m., in person, Gonda 1357)
Speaker: Long Yang
Title: The neurophysiology of gait impairments in Parkinson’s disease: Insights from a mouse model
Summary: Gait dysfunction is a significant complication in Parkinson's disease (PD), exacerbated by existing clinical therapies addressing only a tiny subset of gait impairments. The striatum plays an important role in regulating locomotion. Previous work shows that striatal neurons encode the start and stop of locomotion and movement speed. However, since walking speed results from multiple coordinated limb movements, there is still an incomplete picture of how striatal neurons encode single-limb kinematics on stride by stride level (i.e., gait). Here, using high-resolution, high-speed video tracking (80 fps), we recorded mice freely walking in a large open arena (60 cm x 60 cm). Simultaneous electrophysiological recordings were performed in the dorsal striatum. The large open field enabled mice to walk at a wide range of speeds. We successfully extracted the 2D trajectory of each limb’s position in the arena using open-source machine-learning-based behavioral tracking techniques. This allowed us to examine how neural activity is related to body kinematics at the single-limb level. We then used circular analysis methods to test whether individual neurons are locked to specific phases of the step cycle. Over half of the recorded striatal neurons were significantly entrained to the phase of at least one limb. Furthermore, combined with optogenetic tagging tools, we compared the single-limb phase locking property between D1 and D2 MSNs, the two major neurons in striatum. Healthy mice showed well-balanced D1/D2 single-limb phase locking, which was significantly broken in dopamine-lesioned mice. Specifically, Dopamine-lesion increased the phase-locking strength of D2 MSNs. Taken together, these findings show that striatal neurons represent the phase of individual limb movements, suggesting a more nuanced coding scheme than whole-body speed. This work also opens new avenues for exploring how brain activity during walking is disrupted in movement disorder models.
Relevant Papers:
About Us
Introduction
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 Organizers:
Saray Soldado (Buonomano Lab) & Lukas Oesch (Churchland Lab). Please email us at iclm.journalclub@gmail.com if you would like to get regular updates regarding our journal club and weekly reminders.
Current Faculty Advisor:
Past Organizers:
i) Anna Matynia(Aug 2004 - Jun 2008) (Silva Lab)
ii) Robert Brown (Aug 2008 - Jun 2009) (Balleine Lab)
iii) Balaji Jayaprakash (Aug 2008 - Nov 2011) (Silva Lab)
iv) Justin Shobe & Thomas Rogerson (Dec 2011 - June 2013) (Silva Lab)
v) Walt Babiec (O'Dell Lab) (2013-2014)
vi) Walt Babiec (O'Dell Lab) & Helen Motanis (Buonomano Lab) (2014-2017)
vii) Helen Motanis (Buonomano Lab) & Shonali Dhingra (Mehta Lab) (2017-2018)
viii) Shonali Dhingra (Mehta Lab) (2018-2020)
ix) Megha Sehgal (Silva Lab) & Giselle Fernandes (Silva Lab) (2020-2022)
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