Theory & Data Analysis Tools

Project Abstract This project is a pilot clinical trial of a new brain stimulation treatment for obsessive-compulsive disorder. OCD is a mental illness that affects 4-7 million people in the US. Of those, 50-70% still have substantial symptoms after being treated with medication or talk therapy. Recently, clinicians have started trying to treat OCD with deep brain stimulation (DBS). DBS involves surgically placing electrodes into the brain, then sending electrical stimulation currents through those electrodes.

 DESCRIPTION (provided by applicant): We propose to combine whole brain 2-photon imaging of neural activity in behaving larval zebrafish with detailed anatomical and connectivity information extracted from the same animals. The final goal is to generate quantitative models of brain wide neural circuits that explain the dynamic processing of sensory information as well as the generation of motor output by these circuits. Anatomical data will be generated by two complementary technologies: 1) whole brain EM data sets will be prepared from the same fish that were used for calcium imaging.

 DESCRIPTION (provided by applicant): Perceptual decision-making involves multiple cognitive components and diverse brain regions. To perform a perceptual decision, an individual must process an incoming sensory percept, retain this information in short- term memory, and choose an appropriate motor action. Research using delayed-response tasks in nonhuman primates has revealed that sensory and choice information is distributed across a hierarchy of cortical areas, with task-relevant information flowing from sensory to association to motor regions.

 DESCRIPTION (provided by applicant): Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by the activity of neurons at different levels of information processing? And 2) what features of this activity are read by the higher brain areas to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. To answer the second question, one needs to establish a causal link between neuronal activity and behavior.

 DESCRIPTION (provided by applicant): The goal of the project team is to develop a robust, multi-lab research framework, enabled by large scale imaging, which will lead to principled integrative models of ethologically-relevant behaviors that incorporate a detailed knowledge of individual cell classes. The specific neurobiological question that the team will address is how the brain integrates sensory information in order to guide locomotion in a particular direction.

 DESCRIPTION (provided by applicant): Working memory, the ability to temporarily hold multiple pieces of information for mental manipulation, is central to virtually all cognitive abiliies. Working memory has been closely associated with multiple kinds of neural activity dynamics, such as persistent neural activity, activity ramps, and activity sequences. The neural circuit mechanisms of these dynamics remain unclear.

 DESCRIPTION (provided by applicant): Visual neuroscience is finally beginning to achieve a "vertically integrated" understanding of the retina, bridging all levels from molecules to microcircuits to behavior. Success could be achieved for all retinal microcircuits in just a decade, if progress were sped up drastically. Such acceleration will be attained by generating the following foundational data and disseminating it to the community.

 DESCRIPTION (provided by applicant): The cortex is a laminated structure that is thought to underlie sequential information processing. Sensory input enters layer 4 (L4) from which activity quickly spreads to superficial layers 2/3 (L2/3) and deep layers 5/6 (L5/6) and other cortical areas eventually leading to appropriate motor responses. Sensory responses themselves depend on ongoing, i.e.

 DESCRIPTION (provided by applicant): A key aspect of brain function is how the activity of neuronal populations encodes information that is used to guide behavior. A longstanding model system to understand population coding is the visual cerebral cortex, because its structure and anatomy are well understood, and because visual stimuli can be presented to subjects with high levels of temporal and spatial control.

 DESCRIPTION (provided by applicant): The function of a brain region is an emergent property of many cell types. The criteria needed to understand a network have been established in studies of invertebrate "simple" networks, but there has not yet been an attempt to provide such a full, mechanistic understanding of any network in the vertebrate brain. We believe that the time is now ripe for such an effort. Specifically, we propose to understand how the CA3 network in the hippocampus generates sharp-wave-ripples (SWR).