John H Morrison, PhD
- ADJUNCT PROFESSOR | Neuroscience
Research Topics:Aging, Alzheimer's Disease, Brain, Cognitive Neuroscience, Cytoskeleton, Epigenetics, GABA, Glutamate (NMDA & AMPA) Receptors, Hormones, MRI, Membrane Proteins/Channels, Memory, Motor Neuron, Neural Networks, Neurobiology, Neuroscience, Neurotransmitters, Protein Trafficking & Sorting, RNA Transport & Localization, Receptors, Regeneration, Reproductive Biology, Signal Transduction, Synapses, Synaptic Plasticity, Synaptogenesis, Systems Neuroscience, Transgenic Mice, Transporters, Vision
Dr. Morrison is also the Willard T.C. Johnson Professor of Geriatrics and Palliative Medicine in Neurobiology of Aging, and Professor in the Friedman Brain Institute.
In the News
Please read Dr. John Morrison's Op ED - Science and Medicine in the Service of Society for more information.
Graduate Education in "Accelerating Science, Advancing Medicine"
Please read the message from Dr Morrison regarding Graduate Education in Volume III of "Accelerating Science, Advancing Medicine".
View the PDF.
Winter 2013 Dean's Report
PhD, Johns Hopkins University
Merit Award on Glutamate Receptors in Aging Cortical Circuits
Program Project Grant on Estrogen and the Aging Brain
Specific Clinical/Research Interest: Neurobiology of cognitive aging. Cortical organization, synaptic plasticity, and synaptic alterations with aging. Steroid effects on cortical circuitry, synaptic organization, and function. Neurodegeneration.
PhD: Sarah Motley, Yael Grossman. MD/PhD: Kimberly Kwei. Master: Thomas Chan.
Lab Manager: Bill Janssen; Research Assistants: Rishi Puri, Frank Yuk.
We work on synaptic plasticity, the aging brain, and the synaptic basis of age-related cognitive decline. We are particularly interested in the distinction between Alzheimer's disease (AD) and the more modest disruption of memory often referred to as age-associated cognitive impairment or mild cognitive impairment (MCI) that often occurs in the context of normal aging. While age-associated cognitive impairment represents a major health problem on its own that must be solved, preventing the transition from MCI to AD is a related goal of enormous importance given the rising threat and cost of AD to western society. In order to achieve either goal, we need to understand the cellular, synaptic, and molecular basis of the earliest age-related alterations that lead to cognitive decline and how these events relate to the complex physiology of aging, such as the aging of endocrine systems that affect the brain, or the interactions between stress and aging. For example, in AD, the cortical neurons that provide the complex connections that mediate cognition degenerate, leading to the catastrophic loss of cognitive function evident in dementia. Unlike AD, significant neuron death does not occur in normal aging and thus does not appear to be the cause of the initial stages of age-associated cognitive impairment. While these circuits do not die in normal aging, we have shown that they are vulnerable to sub-lethal age-related alterations in structure, synaptic integrity, and molecular processing at the synapse, all of which impair cognitive function in well-characterized animal models. In addition, while synapse loss occurs in aging, all synapses are not equally vulnerable and all regions do not age the same way. Our recent data on prefrontal cortex show that there is a selective loss of the class of synapses that is most plastic and likely to play a critical role in the cognitive processes mediated by prefrontal cortex, yet the age-related synaptic alterations in hippocampus are quite different, with minimal synapse loss. Biochemical alterations of the synapse, such as shifts in distribution or abundance of key neurotransmitter receptors, may also contribute to memory impairment, particularly in hippocampus.
We have shown that the same brain regions and circuits vulnerable to aging are responsive to circulating estrogen levels, suggesting that critical interactions between reproductive senescence and brain aging may affect excitatory synaptic transmission and cognitive performance. In fact, estrogen treatment in aged female monkeys protected the vulnerable class of synapses and restored cognitive performance to that of young monkeys. Importantly, the effects of estrogen on these neurons show that certain age-associated synaptic alterations may be reversible, leading to the protection of cognitive performance observed in these monkeys. These effects of estrogen give us a molecular and therapeutic entry point to explore additional interventions and strategies to protect against synaptic aging. If we can prevent the synaptic aging of these circuits while still largely intact, we may be able to protect individuals against the earliest stages of cognitive decline and in turn, prevent the transition to the death of these circuits that underlies AD.
A parallel area of research in our lab investigates the effects of behavioral stress on neurons in the prefrontal cortex. We have shown that stress leads to dendritic retraction on pyramidal neurons in prefrontal cortex, and this leads to cognitive decline. Importantly, if stress is discontinued these neurons recover, both structurally and functionally. In addition, the specific neuronal responses to stress differ between males and females. All of these studies were done in young animals, but recently, we were able to link our investigations into neuronal aging with our interest in behaviorally (i.e., stress)- induced plasticity. While the dendrites of prefrontal neurons in young animals recover from stress-induced retraction, this capacity for recovery is absent in middle-aged and aged animals. Furthermore, prefrontal neurons in middle-aged and aged rats lose spines with aging in the absence of stress and are further stress-induced synaptic loss or plasticity. We are now pursuing the mechanisms responsible for age-related loss of experience dependent plasticity.