Project Summary: Project 2 - Linking Fast Timescale Neuron-Astrocyte Communication to Neural Circuit Function and Behavior A fundamental yet unresolved question in neuroscience is how non-neuronal cells communicate with the surrounding neurons, influence their function, and potentially affect animal behavior. Astrocytes are in a unique position to modulate neural circuit function.
SUMMARY / ABSTRACT – Project 1. Multi-feature, Multi-scale Atlas Project 1 of the Berghia Brain Project is to create a multi-scale, multi-feature atlas of the Berghia brain and peripheral neural plexus. Berghia has a brain that is both physically small enough to be serially sectioned and reconstructed from electron micrographs and also has few enough neurons that they can be individually characterized and catalogued.
Program abstract: This proposal aims to identify the neural circuit mechanisms that control periarterial cerebrospinal fluid (CSF) pumping and glymphatic clearance of fluid and solutes. We have developed a collaboration to quantify CSF transport dynamics in both humans and mice across several scales, spanning molecular transport, neuronal and glial activity, vascular and brain-wide fluid dynamics. We propose that coordinated neural activity during sleep drives global and local changes in blood volume, which in turn are the primary drivers of CSF transport.
The heart and the mind: an integrative approach to brain-body interactions in the zebrafish Our current U19 has focused primarily on Exteroception, which can be defined as the accumulated sensory experience originating from events in the outside world. However, all neural computation takes place in the context of the body, which is subject to the dynamics of hunger, fatigue, motivation and diurnal cycles.
PROJECT SUMMARY Many pain syndromes are notoriously refractory to almost all treatment and pose significant costs to patients and society. Deep brain stimulation (DBS) for refractory pain disorders showed early promise but demonstration of long-term efficacy is lacking. Current DBS devices provide “open-loop” continuous stimulation and thus are prone to loss of effect owing to nervous system adaptation and a failure to accommodate natural fluctuations in chronic pain states.
Project Abstract Essential Tremor (ET) is a progressive disease that leads to significant disability and markedly diminished quality of life. Deep brain stimulation (DBS) in the ventralis intermedius (VIM) thalamus has been an effective treatment for ET control, but is associated with problematic side effects (e.g. dysarthia, imbalance) and may lose efficacy over time in people with severe ET. The ability to improve tremor control and reduce side effects with multifocal, current steering DBS techniques will be an important advance to the field.
Gait impairment and Freezing of gait (FOG), lead to falls, injury (even death), loss of independent living, and are common in neurodegenerative diseases such as Parkinson’s Disease (PD), affecting over 7 million people worldwide. The incidence of neurodegenerative diseases increases with age and as the population lives longer, the societal consequences of FOG, will be very significant.
Project Summary/Abstract Post-traumatic stress disorder (PTSD) refractory to treatment is marked by failure of fear extinction and its biological substrate, amygdala reactivity to trauma reminders13,14. Decades of research have clarified the neuronal mechanisms coordinating fear extinction and consolidation15. Fear cells and extinction cells in the basolateral amygdala (BLA) alter their firing rate based on the nature of the stimulus and the influence from the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC)16,17.
A key problem in neuroscience is to uncover fundamental principles and algorithms that allow neuronal networks to perform the complex calculations that underlie normal behavior effectively and efficiently.
Project Summary/Abstract The Research Plan describes a series of experiments that will examine how spatial information is processed in the mammalian brain. Previous studies have identified a population of cells that are tuned to a subject’s directional heading These so-called head direction cells are thought to underlie one’s sense of direction. The neural basis for this computation is believed to reside in an attractor network at subcortical levels.
