PROJECT SUMMARY Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is widely used as a non-invasive technique to study brain function. It operates based on the premise that cerebral blood flow renews the supply of energetic substrates to brain regions with increased neuronal activity in a process known as neurovascular coupling.
ABSTRACT. DART2.0: comprehensive cell type-specific behavioral neuropharmacology Neuro-active drugs have provided hope to millions. However, a major gap in identification of novel therapeutic targets can be attributed to a poor understanding of how neuropharmaceuticals work at the circuit level; in particular, how behavioral effects of drugs are mediated by individual neuron types in the brain.
PROJECT SUMMARY The mammalian brain is arguably the most complex biological structure. Investigating cellular functions and mapping neural connections in the brain are critical tasks to better understand the brain in health and disease. This is particularly challenging in vivo due to the inherent limitations in experimental latitude and simultaneous access to multiple brain regions within the same animal. These shortcomings hinder multimodal interrogation of multi-synaptic circuits and mesoscale connectomics.
PROJECT SUMMARY The use of current and emerging genetically encoded tools could greatly benefit from advanced methods for gene delivery to the desired cell population. When used in conjunction with transgenic animals to restrict expression to cell populations of interest, adeno-associated viruses (AAVs) can provide well-tolerated and targeted transgene expression that enables long-term behavioral, in vivo imaging, and physiological experiments. Lacking from the current suite of vector tools is a way to achieve cell- or circuit-specificity with AAVs without the use of transgenic animals.
PROJECT SUMMARY The brain is the most complex organ in the body, consisting of hundreds of molecularly, physiologically, and anatomically distinct cells. Recently, methods have been developed that can cost-effectively measure mRNA abundance in tens of thousands of single cells, and this has led to a revolution in the identification and classification of new types of cells in the brain. But these methods only measure one aspect of gene regulation – mRNA levels.
Project Summary/Abstract The electroencephalogram (EEG) and magnetoencephalogram (MEG) are directly and instantaneously coupled to the currents across cortical neuronal membranes which mediate information processing. They are widely used for both clinical diagnosis and for investigating the neural mechanisms of cognition with excellent temporal resolution. The goal of this application is to advance our understanding of the relationships between brain imaging signals at the macroscopic levels – EEG and MEG - and the underlying circuits and cellular activity at the fine-grained scales.
DESCRIPTION (provided by applicant): Major breakthroughs in neuroscience have been achieved through the application of computational models to empirical research. Models are essential to connect theory to behavior and the increasingly rich and complex measures of nervous function at multiple spatial and temporal scales. That said, modeling is a highly complex activity requiring extensive training and multiple skills sets, which has created a critica shortfall in the cadre of researchers with the requisite skills to meet the modeling needs in computational neuroscience.
DESCRIPTION (provided by applicant): Truly integrative and interdisciplinary training in neuroscience is necessary to understand brain function in both normal and pathological states. And such training is not available presently at the pre- and post-doctoral and junior faculty level due to a multitude of reasons. We propose an integrated approach to train the next generation of `neuro' research scientists from several disciplines including biology, psychology, medicine, engineering, physics and mathematics.
Project Summary: Hippocampal sharp-wave ripples are 150-250 Hz oscillations during slow-wave sleep or immobility during which large populations of hippocampal neurons sequentially replay activity patterns that occurred during exploration of the environment. Disruption of ripples during wakefulness disrupts working memory.
Our research goal is to determine the factors that instruct the development of visual responses in the mammalian retina. In particular, we are studying the developmental period when the retina transitions from generating retinal waves to mediating visual responses by forming functional circuits. Utilizing a high-speed volumetric two-photon microscope will enable the first description of spontaneous firing patterns across identified microcircuits, such as those that mediate direction selectivity.
