DESCRIPTION (provided by applicant): Understanding communication between neurons, who is talking to whom, and what language they are speaking, is essential for discovering how brain circuits underlie brain function and dysfunction. Over the past decades, Neuroscience has made exponential progress toward recording and imaging communication between neurons.
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): Optogenetics has revolutionized neuroscience by making it possible to use heterologously expressed light-gated ion channels and pumps to stimulate or inhibit action potential firing of genetically selected neurons in order to define ther roles in brain circuits and behavior. Since the flow of information through neural circuits depends on synaptic transmission between cells, an important next technological step is to bring optogenetic control to the neurotransmitter receptors of the synapse.
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): In order to gain a greater understanding of the neural mechanisms that mediate human cognitive function new approaches and technologies are needed to dramatically expand the ability to record and manipulate the activity of large numbers of neurons throughout widespread areas of the primate brain. Over the past 5-10 years, our groups have made two major advances in the study of neural circuits in non-human primates.
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 use of genetically encoded fluorescent activity probes represent the most advanced method to monitor the electrical activity of networks of neurons without using electrodes. While genetically encoded calcium indicators have been evolved to produce robust signals in a variety of different neuronal preparations, fluorescent probes of membrane potential have not been well evolved.
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).
