ABSTRACT BRAIN Initiative-funded, large-scale approaches to classify neurons based on transcriptomic, morphological and electrical properties have unveiled dozens of unique cell classes in the mouse brain.
Electrophysiology is a critical technology in neuroscience as a direct measure of neuronal functions. It has become routine for scientists to record and stimulate neuron populations in different brain regions in awake behaving animals, correlating activity with behavior. However, it has been insurmountable for the same electrophysiology to perform well in the spinal cord of behaving animals.
PROJECT SUMMARY The vertebrate brain has evolved to enable complex social interactions, essential for survival. Brains of animals engaged in a shared social interaction exhibit inter-brain synchronization of neural activity, detectable at several levels of analysis. It remains unclear what aspects of social behavior are driven by these intriguing inter-brain dynamics.
Robust navigation, which is critical for an animal’s survival, requires the processing of complex sensory information spanning different modalities and time scales. Unlike human-engineered systems, where sensors are passive and modularized and decisions are typically made centrally, biological sensors constantly interact and influence each other, and behavioral decisions are made on different time scales with diverse goals. Further, such decisions are based on actively collected sensory information.
ABSTRACT Perceptually guided behavior involves a complex and dynamic interplay between external inputs and internal states that are related, for example, to alertness, motivation, expectations and attention. A wide range of evidence suggests that the representation, processing, and flow of sensory information in the primate brain is regulated by several neuromodulatory systems. However, our understanding of the physiological and behavioral impact of neuromodulatory signals during complex behaviors in primates is quite rudimentary and is lagging behind what is known in rodents.
ABSTRACT ‒ UG3/UH3 Deep Brain Stimulation (DBS), applied to areas like the subthalamic nucleus (STN), is a standard treatment for Parkinson Disease (PD), however, DBS has inherent surgical risks as well as potential for infections and adverse side effects. Our overarching goal is to establish novel chemogenetic neuromodulation strategies in nonhuman primates (NHPs) that utilize and build upon the strengths of DBS but resolve many DBS limitations, and ultimately to translate these to clinical therapies in humans.
ABSTRACT The zebrafish has emerged as a useful model system to discover and characterize genetic and neuronal circuits that regulate vertebrate sleep. However, a limitation of this model is that sleep is determined using behavioral criteria and not the electroencephalogram (EEG) and electromyogram (EMG) measures that are used to define mammalian sleep and wake states.
ABSTRACT We propose to develop a targeted illumination confocal (TICO) microscope to enable high speed, large-scale voltage imaging in the brain. This microscope will be based on the combination of two key strategies. The first strategy is high-speed confocal microscopy based on line scanning. The benefit of confocal microscopy is that out-of-focus background is largely rejected by the use of slit detection. We will supplement this background rejection with the additional strategy of targeted illumination.
PROJECT SUMMARY/ABSTRACT Working memory, the ability to maintain and manipulate in formation in memory over a period of seconds, is a critical component of higher cognitive functions. Neurons in the prefrontal cortex and other brain areas continue to discharge during the maintenance of working memory however, little direct evidence exists on how neurons of different types organize into functional circuits to subserve these functions.
PROJECT SUMMARY/ABSTRACT In humans, damage to a brain region called the retrosplenial cortex leads to pronounced spatial disorientation and severe retrograde and anterograde memory deficits. Similar navigational and memory impairments are also seen in rodents with either lesions or chemogenetic inactivation of the retrosplenial cortex.
