ICLM Journal Club
This Week - 28 January 2022 (9:30 a.m., via Zoom)
Speaker: Mimi La-Vu
Title: “ A genetically-defined population in the lateral and ventrolateral periaqueductal gray selectively promotes flight to safety ”
Abstract: When encountering external threats, survival depends on the engagement of appropriate defensive reactions to minimize harm. There are major clinical implications for identifying the neural circuitry and activation patterns that produce such defensive reactions, as maladaptive overactivation of these circuits underlies pathological human anxiety and fear responses. A compelling body of work has linked activation of large glutamatergic neuronal populations in the midbrain periaqueductal gray (PAG) to defensive reactions such as freezing, flight and threat-induced analgesia. These pioneering data have firmly established that the overarching functional organization axis of the PAG is along anatomically-defined columnar boundaries. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing. However, the PAG contains a diverse arrangement of cell types that vary in neurochemical profile and location. How these cell types contribute to defensive responses remains largely unknown, indicating that targeting sparse, genetically-defined populations can lead to a deeper understanding of how the PAG generates a wide array of behaviors. Though several prior works showed that broad excitation of the lPAG or vlPAG causes freezing, we found in mice that activation of lateral and ventrolateral PAG (l/vlPAG) cholecystokinin-expressing (cck) cells selectively causes flight to safer regions within an environment. Furthermore, inhibition of l/vlPAG-cck cells reduces avoidance of a predatory threat without altering other defensive behaviors like freezing. Lastly, l/vlPAG-cck activity increases away from threat and during movements towards safer locations. In contrast, activating l/vlPAG cells pan-neuronally promoted freezing and these cells were activated near threat. These data underscore the importance of investigating genetically-identified PAG cells. Using this approach, we found a sparse population of cck-expressing l/vlPAG cells that have distinct and opposing function and neural activation motifs compared to the broader local ensemble defined solely by columnar anatomical boundaries. Thus, in addition to the anatomical columnar architecture of the PAG, the molecular identity of PAG cells may confer an additional axis of functional organization, revealing unexplored functional heterogeneity.
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:
Megha Sehgal (Silva Lab) & Giselle Fernandes (Silva 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)
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