Monitoring Communication in Neuronal Networks in Real Time and at Single Cell Resolution

2018 Seed Grant
Andre Berndt, Ph.D.
University of Washington

Visualizing the flow of information through the complex and intertwined networks of the brain is a long‐sought goal of neuroscience. Genetically encoded proteins such as the fluorescent calcium sensor GCaMP provide tremendous advantages for analyzing neuronal activity. Protein expression can be restricted to specific neuronal subtypes enabling us to probe their function in isolation from surrounding cells in real time and with single cell resolution. Consequently, we could dissect brain function in even more detail by visualizing crucial signals such as action potentials or neurotransmitter release. However, the number of sensors that provide applicable readout capabilities is limited, and new designs depend on slow and iterative engineering cycles. We have built one of the fastest platforms for functional screening of voltage and ligand‐activated sensors. We hypothesize that the significant increase in testing throughput will allow us to generate a new generation of applicable tools at unprecedented speeds. We propose to rapidly develop novel fluorescent protein sensors for quantifying the excitatory and inhibitory activity of neuronal networks. We will utilize these new sensors in much faster timeframes and directly monitor the impaired excitatory and inhibitory activity in mouse models with severe autistic and epileptic phenotypes. Monitoring impaired network dynamics in real time and at large scale will close critical knowledge gaps in our understanding of the physiology underlying neuronal dysfunction. These insights will be crucial for developing therapies and interventions which could significantly improve the outcome of patients and their caregivers.

Other Grants

Denise Cai, Ph.D.
Investigating the Role of Negative Valence in the Temporal Dynamics of Memory-Linking
Determining how distinct memories are formed, linked, and retrieved, and the role of fear in these processes, is an essential part of understanding PTSD, a debilitating disorder characterized by the…
Dr. Weizhe Hong, Ph.D.
Dissecting the Organization and Function of Social Behavioral Circuits in the Amygdala
Social interactions play a crucial role in the reproduction, survival, and physical and mental health of many vertebrate species including humans. Impairment in social behavior is a hallmark of several…
Takashi Kitamura, Ph.D.
Neural Circuit Mechanisms of Behavior-Dependent Representation for Space and Time
The central question in my proposal is whether our perception of time and space share the same circuit mechanisms during our daily life. Recent studies suggest that neurons in the…
Sheng-Han Kuo, M.D.
Aberrant Synaptic Organization in Tremor Disorders
Tremor is a prevalent and often debilitating disorder for many individuals; however, the cause of tremor remains poorly understood. We have previously identified alterations in the cerebellum, the brain region…