Periodic Reporting for period 1 - ThaCSIS (Thalamic Control of Sensory Information Selection)
Reporting period: 2021-11-01 to 2023-10-31
At any moment, we are exposed to a multitude of sensory inputs, among which we need to select and process the relevant information. A significant function of the cerebral cortex is to process sensory inputs, prioritizing the most behaviorally relevant signals over less important ones, enabling an appropriate action selection and behavioral response. This selective sensory processing is disrupted in a range of neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD), where individuals cannot properly filter simultaneous sensory inputs. Neuroimaging and neurophysiological studies have suggested selective sensory processing involves the coordinated action of the thalamus across an interconnected network of cortical areas. Despite the importance of sensory selection, the neural circuit mechanisms that allow the selective processing of sensory inputs, especially across sensory modalities, remain largely unknown.
This project aims to reveal the coordinated activity across sensory cortical regions that allow sensory selection and the role of the thalamus in shaping these interactions. To achieve this goal, I have developed a well-controlled sensory detection assay in mice that allows probing of interactions across sensory visual and somatosensory modalities during sensory selection. I measure large-scale cortical activity to reveal how sensory signals flow in a cortex-wide circuit and how behavioral relevance shapes this flow. Simultaneous optogenetic manipulations of the thalamus reveal its role in cortical reorganization. The results of this work reveal how the cortex and thalamus reconfigure their activity to highlight the most relevant sensory information, as well as provide a mechanistic understanding of what neural circuits drive selective behavioral responses.
This project aims to reveal the coordinated activity across sensory cortical regions that allow sensory selection and the role of the thalamus in shaping these interactions. To achieve this goal, I have developed a well-controlled sensory detection assay in mice that allows probing of interactions across sensory visual and somatosensory modalities during sensory selection. I measure large-scale cortical activity to reveal how sensory signals flow in a cortex-wide circuit and how behavioral relevance shapes this flow. Simultaneous optogenetic manipulations of the thalamus reveal its role in cortical reorganization. The results of this work reveal how the cortex and thalamus reconfigure their activity to highlight the most relevant sensory information, as well as provide a mechanistic understanding of what neural circuits drive selective behavioral responses.
The EU-funded ThaCSIS project aims to reveal neural circuits that allow selecting the right information at the right time. My approach towards achieving this goal is first uncovering how sensory signal flow in a cortex-wide network is shaped by different contexts and then testing whether the higher-order thalamic nucleus plays a role in the reorganization and sensory gating. To answer these questions, we have successfully developed a behavioral assay in which head-restrained mice learn to perform visual or tactile detection tasks in sequential blocks. Optogenetic suppression of posterior cortical areas deteriorated behavioral performance, indicating that cortical activity is necessary for performing the task. We measured responses to the same sensory stimuli under different behavioral conditions (passive, visual, tactile context) to identify differential cortical activity patterns in task-dependent sensory signal processing. We observed that behavioral training decreases sensory responses to sensory stimulation, and overall cortical activity patterns vary across contexts, although sensory stimulation remains identical. We are also employing correlation-based analysis to identify differences in functionally connected networks (using transfer entropy) to reveal key brain regions that exhibit differential connectivity, suggesting their involvement in task-dependent modulations of sensory signal processing. We aim to finalize our results on changes in cortical dynamics by the end of 2024.
We have established chronic electrophysiological recordings using multi-shank Neuropixel 2.0 probes to characterize task-dependent modulations of thalamic activity. This approach will allow us to acquire data from thalamic nuclei and an extensive set of subcortical regions at the cellular level with high temporal resolution. To investigate the causal role of thalamic nuclei in sensory selection and driving changes in cortical activity patterns, we established optogenetic suppression of the thalamic nuclei while simultaneously observing behavior and cortical activity through imaging methods.
The results of this project were communicated to the expert audience at an international neuroscience meetings (International Multisensory Research Forum 2023) and through invited talks (Brain Research Institute, University of Zurich, Switzerland 2022 and Turkish Neuroscience Meeting, 2023). Two manuscripts for disseminating results of the project are in preparation: one publication on the context-dependent reorganization of cortical activity patterns and cellular responses underlying global dynamics and the second one on the role of higher-order thalamic nucleus. The project activities are communicated to the general public via press releases, social media outlets, and on the project webpage.
We have established chronic electrophysiological recordings using multi-shank Neuropixel 2.0 probes to characterize task-dependent modulations of thalamic activity. This approach will allow us to acquire data from thalamic nuclei and an extensive set of subcortical regions at the cellular level with high temporal resolution. To investigate the causal role of thalamic nuclei in sensory selection and driving changes in cortical activity patterns, we established optogenetic suppression of the thalamic nuclei while simultaneously observing behavior and cortical activity through imaging methods.
The results of this project were communicated to the expert audience at an international neuroscience meetings (International Multisensory Research Forum 2023) and through invited talks (Brain Research Institute, University of Zurich, Switzerland 2022 and Turkish Neuroscience Meeting, 2023). Two manuscripts for disseminating results of the project are in preparation: one publication on the context-dependent reorganization of cortical activity patterns and cellular responses underlying global dynamics and the second one on the role of higher-order thalamic nucleus. The project activities are communicated to the general public via press releases, social media outlets, and on the project webpage.
My goal in this project is to uncover the underlying reorganization of cortical processing upon change in behavioral context at the network (global) and cellular (local) levels, as well as test a possible driver mechanism (Figure). For this, we established a visual-tactile multisensory behavioral paradigm consisting of the same set of sensory stimuli, where the rewarded sensory modality will determine the behavioral context. Our large-scale cortical activity data provides evidence for network reorganization upon change in behavioral context. Beyond characterizing the reorganization patterns across the cortex, our cellular data will reveal what modulations in cellular activity patterns underly change at the network level. With mesoscale 2P imaging, neural activity patterns at the cellular resolution could reveal what underlies changes, decreases, or increases in functional connectivity. Cellular mechanisms underlying functional connectivity changes can also provide mechanistic explanations for the functional connectivity changes obtained in human neuroimaging studies where invasive approaches are unavailable.
Also, simultaneous silencing and population imaging would reveal the impact of higher-order thalamic nuclei in large-scale cortical dynamics and whether these changes are context-dependent. Moreover, understanding cortical activity reorganization in response to (multi-modal) sensory stimulation and its contextual prioritization can allow us to identify neural circuit dysfunction patterns in neurodevelopmental disorders. We have recently initiated a project exploring differences in brain-wide response patterns to sensory stimuli in a monogenic autism mouse model.
Furthermore, the developed multisensory stimulation experimental and analysis pipeline will be exploited in a recently established In vivo Neurophysiology Core Unit, to explore large-scale circuit dysfunction patterns in a wide range of projects, including brain disease models.
Also, simultaneous silencing and population imaging would reveal the impact of higher-order thalamic nuclei in large-scale cortical dynamics and whether these changes are context-dependent. Moreover, understanding cortical activity reorganization in response to (multi-modal) sensory stimulation and its contextual prioritization can allow us to identify neural circuit dysfunction patterns in neurodevelopmental disorders. We have recently initiated a project exploring differences in brain-wide response patterns to sensory stimuli in a monogenic autism mouse model.
Furthermore, the developed multisensory stimulation experimental and analysis pipeline will be exploited in a recently established In vivo Neurophysiology Core Unit, to explore large-scale circuit dysfunction patterns in a wide range of projects, including brain disease models.