Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors
Processing sensory information to generate decisions and action is a central component of learned, goal-directed behavior. Even during ongoing sensory-motor processing, our sensory landscape is fltered through our prior expectations and ongoing goals. This active perceptual process hinges on a distr...
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| Other Authors: | |
| Format: | Thesis |
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Massachusetts Institute of Technology
2024
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| Online Access: | https://hdl.handle.net/1721.1/153321 |
| _version_ | 1811090863614328832 |
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| author | Leow, Yi-Ning |
| author2 | Sur, Mriganka |
| author_facet | Sur, Mriganka Leow, Yi-Ning |
| author_sort | Leow, Yi-Ning |
| collection | MIT |
| description | Processing sensory information to generate decisions and action is a central component of learned, goal-directed behavior. Even during ongoing sensory-motor processing, our sensory landscape is fltered through our prior expectations and ongoing goals. This active perceptual process hinges on a distributed network of cortical and subcortical areas. The pulvinar, or homologous rodent lateral posterior (LP) nucleus, is a higher-order visual thalamic nucleus that bridges many of these subcortical and cortical structures. In particular, LP/pulvinar interactions with the prefrontal cortices such as the anterior cingulate cortex (ACC) have been implicated in regulating attentional processes. However, the anatomical inputs integrated and precise information carried by this projection during decision-making and action-selection has never been clarifed. We address this gap by leveraging genetic tools available in mouse models to examine the role of LP-ACC inputs directly with projectionspecifc anatomical mapping, axonal calcium imaging with two-photon microscopy in animals viewing visual stimuli passively or performing a decision task, and optogenetic manipulations. We fnd that LP-ACC axons integrate inputs from a vast network of subcortical and cortical structures that are implicated in attention, visuomotor functions, and spatial cognition. During passive viewing, activity of the LP-ACC projection is dominated by global arousal states while visual information is poorly represented. During a two-alternative graded random dot motion direction discrimination task, LP-ACC activity in individual axons and the axonal population represents multiple task variables. The activity of single axons ranges from the coding of stimulus coherence and direction in the random dot stimuli to the signaling of diferent task epochs in individual trials. At the population level, we fnd highly structured representations of task variables: LP-ACC activity jointly represents direction and coherence of visual stimuli in a low-dimensional geometric manifold that facilitates visual decoding. Furthermore, LP-ACC axons dynamically represent the outcome and uncertainty of previous trials, and integrate past and current trial uncertainty throughout the task. These physiological responses infuence trial-by-trial behavior, which can be disrupted by optogenetic perturbation of specifc trial epochs. Our fndings demonstrate that the LP contributes to attention and decision-making by providing a read-out of ongoing uncertainty, integrated over time with behavioral history, to adaptively tune neuronal responses and guide goal-directed behavior on a trial-to-trial basis. |
| first_indexed | 2024-09-23T14:53:10Z |
| format | Thesis |
| id | mit-1721.1/153321 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:53:10Z |
| publishDate | 2024 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1533212024-01-17T03:15:39Z Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors Leow, Yi-Ning Sur, Mriganka Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Processing sensory information to generate decisions and action is a central component of learned, goal-directed behavior. Even during ongoing sensory-motor processing, our sensory landscape is fltered through our prior expectations and ongoing goals. This active perceptual process hinges on a distributed network of cortical and subcortical areas. The pulvinar, or homologous rodent lateral posterior (LP) nucleus, is a higher-order visual thalamic nucleus that bridges many of these subcortical and cortical structures. In particular, LP/pulvinar interactions with the prefrontal cortices such as the anterior cingulate cortex (ACC) have been implicated in regulating attentional processes. However, the anatomical inputs integrated and precise information carried by this projection during decision-making and action-selection has never been clarifed. We address this gap by leveraging genetic tools available in mouse models to examine the role of LP-ACC inputs directly with projectionspecifc anatomical mapping, axonal calcium imaging with two-photon microscopy in animals viewing visual stimuli passively or performing a decision task, and optogenetic manipulations. We fnd that LP-ACC axons integrate inputs from a vast network of subcortical and cortical structures that are implicated in attention, visuomotor functions, and spatial cognition. During passive viewing, activity of the LP-ACC projection is dominated by global arousal states while visual information is poorly represented. During a two-alternative graded random dot motion direction discrimination task, LP-ACC activity in individual axons and the axonal population represents multiple task variables. The activity of single axons ranges from the coding of stimulus coherence and direction in the random dot stimuli to the signaling of diferent task epochs in individual trials. At the population level, we fnd highly structured representations of task variables: LP-ACC activity jointly represents direction and coherence of visual stimuli in a low-dimensional geometric manifold that facilitates visual decoding. Furthermore, LP-ACC axons dynamically represent the outcome and uncertainty of previous trials, and integrate past and current trial uncertainty throughout the task. These physiological responses infuence trial-by-trial behavior, which can be disrupted by optogenetic perturbation of specifc trial epochs. Our fndings demonstrate that the LP contributes to attention and decision-making by providing a read-out of ongoing uncertainty, integrated over time with behavioral history, to adaptively tune neuronal responses and guide goal-directed behavior on a trial-to-trial basis. Ph.D. 2024-01-16T21:50:55Z 2024-01-16T21:50:55Z 2023-06 2023-10-17T14:43:39.939Z Thesis https://hdl.handle.net/1721.1/153321 In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology |
| spellingShingle | Leow, Yi-Ning Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors |
| title | Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors |
| title_full | Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors |
| title_fullStr | Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors |
| title_full_unstemmed | Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors |
| title_short | Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors |
| title_sort | multiplexed representations of uncertainty by mouse pulvinar prefrontal projections during goal directed behaviors |
| url | https://hdl.handle.net/1721.1/153321 |
| work_keys_str_mv | AT leowyining multiplexedrepresentationsofuncertaintybymousepulvinarprefrontalprojectionsduringgoaldirectedbehaviors |