ICLM Journal Club
This Week - 14 December 2018 (9:30 a.m., Gonda 2nd Floor Conference Room)
Speaker: Helen Motanis
Title: Network activity of Fragile X circuits
Abstract: Fragile X syndrome (FXS) is the most common inherited learning disability disorder and is characterized by developmental delays. Here we use an in vitro approach to study network level abnormalities in FX circuits, such reduced systems help bridge molecular/cellular and systems levels of analyses, and observed deficits are less likely to be a consequence of differences in nurture or compensatory mechanisms. First we found that developmental delays are indeed observed in vitro: both whole-cell recordings and 2-photon calcium imaging revealed that FX circuits exhibited a significant developmental delay of spontaneous network activity that was specific to the emergence of Up-states. In contrast to younger FX circuits, mature circuits revealed normal spontaneous activity. These findings are the first to confirm the presence of an in vitro developmental delay in FX circuits.
Mechanistically, the early decrease in spontaneous activity was not associated with a decrease in evoked EPSP strength. However, evoked EPSP strength was reduced in mature FX circuits confirming another developmental delay.
We also examined network-level homeostatic plasticity by using chronic optogenetic stimulation to emulate an increase in externally driven activity. Both WT and FX circuits exhibited normal homeostatic plasticity of evoked and spontaneous activity.
Lastly and because FX is mainly characterized as a learning disability, we established two protocols of in vitro ‘temporal learning’. These protocols were based on a combination of optical and electrical stimulations that allowed us to establish interval/temporal learning in WT circuits. Preliminary data suggest that FX circuits show deficits in this type of in vitro learning.
Our results revealed multiple waves of developmental delays in FX circuits: first a delay in spontaneous activity, followed by a delay in evoked EPSP strength. In addition, our results indicate that FX circuits are able to adapt to relatively simple forms of learning (normal homeostatic plasticity) but not to forms of learning that require the circuits to do major network reorganizations (deficits in temporal learning). These results hint to the possibility that some previously described neural phenotypes observed in FX may be compensatory.
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.
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