Training

PROJECT SUMMARY / ABSTRACT Memory is an integral component of human cognition, and when memory processes go awry, the result is devastating neurological disorders of memory loss including Alzheimer's disease and other forms of dementia. One essential role of normal memory processes is to use previous experience to guide decisions about future actions. Thus, research to define the neural mechanisms of memory processes is important to understand both normal brain function and what goes wrong in memory loss disorders.

Project Abstract/Summary This application describes a 3-year training plan that will enable me, a cognitive neuroscientist with prior training in electroencephalography (EEG), to conduct research on contextual memory representation using neuroimaging (fMRI) and computational modeling. EEG is useful for examining the timing properties of neural activity, but cannot localize activity to specific regions of the brain.

Project Summary Alarming shortcomings of the bedside behavioral examination in reliably detecting consciousness generate profound dilemmas for clinicians and families facing decisions about continuation of life-sustaining therapy, pain control, prognostication, and resource allocation in patients with disorders of consciousness (DoC).

The ability to non-invasively perturb specific regions deep in the human brain would enable researchers and clinicians to study the causal relationships between specific brain structures and behavior. Current non-invasive neuromodulatory techniques enable the perturbation of the human cortex but a method that is simultaneously non-invasive, focal, and capable of perturbing deep brain circuits remains elusive. The goal of this project is to develop a non-invasive and focal technique capable of perturbing individual deep brain nuclei in humans.

Localized structuring of neuronal output by inhibitory microcircuits is a fundamental component of neuronal information processing. Interneuron subpopulations contained within these microcircuits integrate afferent excitatory and inhibitory inputs, transforming these external signals into broad modulatory effects. Simple on-off dichotomies do not accurately account for the modeled variations in interneuron activity resulting from excitatory or inhibitory inputs alone.

Project Summary/Abstract Behaviors essential for survival, including parenting behaviors, are driven by neural circuits that arise from combinations of genetics and experience-dependent learning. To what extent is parental behavior learned, vs. predetermined by innate specializations of neural circuits? Virgin female mice can learn some maternal behaviors when housed with an experienced mother and her pups, in particular retrieving isolated pups to the nest. Preliminary data indicates that virgins can learn this behavior via auditory and visual observation.

Project Summary The hippocampus is a critical site for rapid memory formation and retrieval, with extensively documented functions representing spatial and navigational variables, yet less is known of the means by which it guides behavior.

Project Summary Walking is an essential and conserved behavior across the animal kingdom. The ability to move in a coordinated, robust yet flexible manner is a crucial for an animal’s survival in the ever changing environment. Motor behaviors are controlled by sensory neuropils in the brain which talk to motor centers such as the ventral nerve cord (VNC) in the thorax to execute precise motor outputs. Descending neurons are the primary conduits of information that accomplish this connection between the brain and the VNC.

Cortical circuits perform computations to generate appropriate behaviors based upon diverse sensory inputs. These computations are central to an animal maintaining its health and long- term survival. An example of this type of computation are perceptual decision-making tasks where an animal must weigh sensory evidence to choose a behavior which will elicit a reward. The classical circuit models of decision-making focus solely on the effects of recurrent excitation, treating inhibitory neurons as agnostic facilitators of competition between excitatory subpopulations.

Project Summary/Abstract Astrocytes comprise up to half of mammalian brain cells. Accumulating evidence from multiple brain circuits suggests that astrocytes, through their intracellular Ca2+ signaling, regulate and modulate neuronal activity on single-cell and network-wide levels and on a broad range of timescales—from milliseconds to days and weeks. Altered astrocyte Ca2+ signaling has also been implicated in a variety of brain disorders, including Huntington’s Disease, Alzheimer’s Disease, obsessive-compulsive disorder, stroke, and epilepsy.