Memory and Cognitive Disorders Awards
Nicole Calakos, MD, PhD, Associate Professor of Neurology and Neurobiology, and Henry Yin, PhD, Assistant Professor of Psychology and Neuroscience, Duke University
From good habit to bad: Examining the relationship between habit learning and compulsivity
Calakos and Yin are exploring how the pattern of firing activity among distinct cell types in the basal ganglia changes with learning. Although much is known about what goes on at synaptic connections in the brain during the learning process, much less is known about how these changes are integrated to influence neuronal firing among populations of neurons in a given circuit. The researchers have developed an approach to examine learning at this level and will apply it to examine how neural activity changes in the striatum as habits are learned and whether an aberration of the normal habit learning process leads to compulsive behaviors. This work has potential to improve our understanding of how habit learning is encoded in the striatum and how the process may be disrupted in obsessive compulsive disorder (OCD) and related disorders.
Edward Chang, MD, Associate Professor of Neurological Surgery and Physiology, University of California, San Francisco
How we learn words: the neurophysiology of verbal memory
In childhood and adulthood, we build and maintain massive vocabularies, but we don’t know exactly how. Because language is unique to humans, Chang plans to study the mechanisms of word learning in people—specifically, patients who are undergoing neurosurgical procedures and have electrodes implanted in their brains for clinical indications, such as epilepsy localization. He hopes to gain important new knowledge about how brain networks are coordinated in learning words. Because word-finding difficulties are a common symptom related to aging and many neurological conditions, such as Alzheimer's disease, stroke and aphasia, new treatments that can preserve or enhance brain function in these conditions will depend on understanding how words are learned.
Adam Kepecs, PhD, Associate Professor, Cold Spring Harbor Laboratory
Cell-type specific cognitive broadcast signals from the nucleus basalis
Kepecs’ lab is studying the nucleus basalis (NB), a vitally important but poorly understood neuromodulatory system whose degeneration parallels the decline of cognitive functions in patients with Alzheimer’s disease, Parkinson’s dementia and normal age-related cognitive decline. There is evidence that NB has roles in learning and attention but it is not known what signals this system sends to the cortex. To obtain fundamental knowledge about it, Kepecs will record identified cholinergic NB neurons in behaving mice. The research, which combines behavioral electrophysiology, quantitative psychophysics and optogenetic techniques, will determine what specific neurons signal and when, and whether they have the appropriate signals to support learning and attention. Knowledge of the firing patterns in these neurons will provide critical information for the development of therapeutic treatments for cognitive diseases.
John Wixted, PhD, Distinguished Professor of Psychology, and Larry Squire, PhD, Professor of Psychiatry, Neurosciences and Psychology, University of California, San Diego
The representation of episodic and semantic memory in single neurons of the human hippocampus
The investigators are exploring whether individual neurons in different subregions of the human hippocampus encode memories. The question of how the brain stores memories has been examined using other methodologies, but all have had limitations. For this research, Wixted and Squire are collaborating with Dr. Peter Steinmetz at the Barrow Neurological Institute to ask patients to memorize a series of pictures and/or words. The scientists will measure single neuron activity in different areas of the hippocampus as the patients later remember those items. The long-term goal is to create a foundation for the development of clinical interventions designed to slow the memory impairment associated with aging and to slow the progression of neurodegenerative diseases in the hippocampus that profoundly impair the ability to remember.
Alison Barth, PhD, Carnegie Mellon University
Cell-specific capture of experience-dependent plasticity in the neocortex
Using a mouse model that permits targeted electrophysiological recordings of neocortical circuits, Barth will work to identify specific neurons changed by experience and look at synaptic inputs to these cells, and also to try to drive changes in a certain subset of cells in vivo. The central question is how does experience transform cells and connections between cells, and what about this process is so critical for learning and memory.
Charles Gray, PhD, Montana State University
Distributed processing underlying cognition
Gray’s lab has just developed an instrument that can measure neural activity in rhesus monkeys at a very high temporal and spatial resolution from many locations. During the award period, Gray plans to measure neural activity from large areas of the brain to obtain a broad perspective on how and where information is encoded when the brain is holding something in short-term memory.
Geoffrey Kerchner, MD, PhD, and Anthony Wagner, PhD, Stanford University
Hippocampal structure and function in cognitive impairment
Kerchner plans to use two high-resolution magnetic resonance imaging (MRI) technologies to study the interlinked subregions of the hippocampus to see how they are affected in Alzheimer’s disease. He will study the physical structure of the hippocampus with one technology and, in collaboration with Wagner, will use the other technology to study how groups of hippocampal nerve cells fire during memory exercises.
Attila Losonczy, MD, PhD, Columbia University
Dissecting hippocampal microcircuit dysfunctions underlying cognitive memory deficits in schizophrenia
Losonczy aims to advance understanding of memory processes in healthy and diseased brains to identify key targets for preventing and treating these memory deficits. Using mouse models, he plans to use state-of-the-art in vivo functional imaging to observe and manipulate neural circuits in the rodent hippocampus during memory behaviors, tracking how these neurons function in normal learning and how they are altered in schizophrenia.
Ben Barres, MD, PhD, Professor of Neurobiology, Stanford University School of Medicine
Do Astrocytes Control Synaptic Turnover? A New Model for What Causes Alzheimer’s Disease and How to Prevent It
As our bodies age, it’s likely that some mechanism is needed to remove aging synapses in the brain so they can be replaced with new ones. Barres is investigating whether astrocytes play this role and, if so, what happens if their work is impaired. The work has potential to improve understanding and treatment of Alzheimer’s disease.
Wen-Biao Gan, PhD, Associate Professor of Physiology and Neuroscience, New York University School of Medicine
Microglial Function in Learning and Memory Disorders
Gan is investigating whether microglia play an important role in learning and memory formation. Using a new transgenic mouse line he developed, he will examine how eliminating microglia or making them dysfunctional affects neural circuits. The studies will provide insights for the understanding and treatment of brain disorders such as autism, mental retardation and Alzheimer’s disease.
Elizabeth Kensinger, PhD, Associate Professor of Psychology, Boston College
Changes in the Temporal Dynamics and Connectivity of Emotional Memory Networks Across the Adult Lifespan
Kensinger is studying the impact of emotions on memory. Her research takes a lifespan perspective, assessing memory and neural activity of adults ages 18-80. She will examine how emotional information is retrieved, including both the spatial and temporal dimensions of memory retrieval. The research has potential to advance understanding of the memory changes associated with age, as well as such disorders as depression and post-traumatic stress syndrome.
Brian Wiltgen, PhD, Assistant Professor of Psychology, University of Virginia
Reactivation of Neocortical Memory Networks During Consolidation
New memories are encoded by the hippocampus and over time are permanently stored in regions of the neocortex. Wiltgen is exploring the biological mechanisms that underlie this storage process, using new techniques to control the activity of memory circuits in the hippocampus and neocortex. The work has implications for the treatment of Alzheimer’s and other diseases that affect memory.
Cristina Alberini, PhD, Professor of Neuroscience, Mount Sinai School of Medicine
The Role of Astrocytes in Memory and Cognitive Disorders
Alberini is focusing on the interaction between neurons and astrocytes in memory formation. She will explore the hypothesis that defects in this interaction may cause cognitive impairments and look at potential new treatments for the cognitive decay related to aging and neurodegeneration.
Anis Contractor, PhD, Assistant Professor of Physiology, Northwestern University School of Medicine
Activating Group I mGluRs to Repress Fear Memory
Mice lacking the glutamate receptors called mGluR5 cannot extinguish fearful memories. Contractor plans to study the role of these receptors, mapping the brain circuits involved in learning to fear appropriate situations and to suppress inappropriate fear. He will also see if new drugs can accelerate the process of learning not to be excessively afraid. Similar drugs may be useful in treating human anxiety disorders.
Loren Frank, PhD, Assistant Professor of Physiology, and Mary Dallman, PhD, Professor Emerita of Physiology, University of California, San Francisco
A Circuit Level Approach to Understanding & Treating Stress-Related Memory Disorders
Frank and Dallman are examining whether small alterations in brain activity could help minimize the long-lasting effects of stress on learning and memory. If their hypothesis that stress amplifies the replay of memories proves to be the case, therapies could be designed to reduce the long-lasting effect of stressful events. The research has particular implications for post-traumatic stress disorder.
Michael Mauk, PhD, Professor, and Daniel Johnston, PhD, Professor and Director, Center for Learning and Memory, University of Texas at Austin
Cortical Persistent Activity Mechanisms of Working Memory
Mauk and Johnston will use both systems and cellular approaches to study working memory both in living animals and in brain slice experiments using powerful neuron recording methods. Because working memory contributes to so many cognitive processes, understanding its mechanisms could improve diagnosis and treatment of many disorders, including Alzheimer's disease and ADHD.