ICLM Journal Club
This Week - 18 January 2019 (9:30 a.m., Gonda 2nd Floor Conference Room)
Speaker: Anubhuthi Goel
Title: Dissecting Circuit Dynamics of Sensory Discrimination and Behavior
Abstract: In order to make sense of the continuous stream of incoming sensory information the cortex must learn to discriminate between a myriad of different stimuli. This sensory discrimination relies on the spatial (e.g., the orientation of a line) and temporal (e.g., duration) features of stimuli. For example, discriminating the orientation of visual stimuli is critical for playing sports, driving or judging emotions, while estimating intervals and durations is important for anticipating the onset of a predator’s actions, the duration of traffic lights, or prosody. Sensory discrimination is thus fundamental for learning and memory, and generating complex behavior, although our understanding of the mechanistic link is limited. In particular the question of how are the temporal features of stimuli or a stimulus duration represented in the brain remains largely unanswered? Theoretical and psychophysical studies suggest that temporal intervals in sensory input are encoded in the changing pattern of active neurons or the evolving population response within a local recurrent network. Using a novel and radical ‘learning in a dish’ model, I trained networks in vitro on different temporal intervals, and showed that the temporal pattern of experience was indeed encoded in the network dynamics, as a result of time window specific modification of excitatory – inhibitory (E-I) balance. The fundamental importance of optimal sensory discrimination is evident in disorders such as autism and autism spectrum disorders (ASD), where sensory processing impairments are often observed. To test the idea that abnormal sensory discrimination contributes to higher order cognitive impairments I used Fmr1-/- mice, a mouse model of autism, and a go/no-go visual perceptual discrimination task for head-restrained mice, and discovered that, compared to wild-type (WT) mice, Fmr1-/- mice take significantly longer to discriminate between gratings drifting in two orthogonal orientations (90o task). The delayed learning was mediated by a reduction in the number of orientation selective cells in primary visual cortex (V1) and reduced parvalbumin (PV) cell functional output, potentially contributing to abnormal E-I balance. A chemogenetic strategy restored PV cell output and rescued behavior. Importantly, for the first time in the field of autism, using analogous sensory discrimination paradigms both in mice and humans, I found that human subjects with FXS exhibit similar impairments in visual discrimination, as Fmr1-/- mice. These findings highlight the contribution of balanced and task dependent E-I changes in encoding sensory input and suggest that simple therapeutic strategies that dynamically restore the E-I balance in cortical circuits may be of value in treating specific behavioral impairments.
My future goals include delineating the network dynamics underlying sensory discrimination of temporal intervals and sequences, and how this impacts learning in normal as well pathological conditions.
Relevant Paper(s): https://www.nature.com/articles/s41593-018-0231-0/
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:
Consult the User's Guide for information on using the wiki software.