Systems Neuroscience

PROJECT SUMMARY In social species, social relationships can exert profound influences on individuals’ behavioral and physiological states. In particular, social interactions can help reduce negative emotional state induced by physical or psychological stressors, a phenomenon known as social buffering. Social buffering provides an important means by which the social environment facilitates stress coping and resilience and benefits health and well-being.

Abstract Sleep occupies a large part of our lives and is widely believed to perform essential functions. During sleep, the neuronal rules of engagement and population dynamics are clearly different than waking. There is extensive evidence that one primary function of sleep is to consolidate memories formed during waking. Recent work, however, suggests that sleep may also actively alter neural connections to achieve forgetting (‘unlearning’). How the brain balances learning and forgetting, exactly how sleep contributes, and the ultimate effects on ensembles and behavior are unknown.

PROJECT SUMMARY Survival in dynamic environments demands that behaviors are flexible and adaptive. An organism must make predictions about which actions lead to rewards, calculate how outcomes differ from those predictions (prediction errors), and adapt a behavioral strategy accordingly. Neurons encoding prediction errors can be found throughout many reward-related brain structures, with the highest densities in the VTA and the lateral habenula (LHb).

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.

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 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.