John H. Morrison

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.

Current Students: PhD: Athena Wang, Erik Bloss, Megan Bailey. MD/PhD: Dani Dumitriu, Kimberly Kwei.

Postdoctoral Fellows: Rebecca Shansky and Yuko Hara.

Research Personnel: Lab Manager: Bill Janssen; Research Assistants: Shannon Wadsworth, Dan Ohm, and Rishi Puri.

Current Research
Neurobiology of Aging, Cellular and Synaptic Organization of Cerebral Cortex, Estrogen and the Aging Brain, Cognitive Aging, and Neurodegenerative Disorders
Our research program includes several related components, with the three primary areas being the cellular and synaptic organization of cerebral cortex, selective vulnerability in neurodegenerative disorders, and age-related alterations in glutamate receptor-mediated cortical circuits. These efforts involve cellular neuropathologic analyses of human brain, experimental and neuropathologic analyses of non-human primate and rat cortex, and detailed analyses of genetically manipulated mice. In both neocortex and hippocampus, we are particularly interested in determining the molecular and structural nature of age-related alterations in synaptic plasticity that lead to compromised cognitive function. We are particularly interested in age-related synaptic alterations and how the mechanism of such alterations differs from the degenerative cascade of Alzheimer’s disease. Virtually all of our microscopic analyses are quantitative in nature and through collaborations with cognitive neuroscientists, we are able to link quantitative cellular and synaptic measurements with cognitive performance in the same subjects.

Our studies on glutamate receptor-mediated circuits have focused on both neocortex and hippocampus of primates and rodents. Recently, we have been particularly interested in the cellular and molecular events underlying the functional decrements often seen in normal aging, particularly age-related memory impairment. In contrast to Alzheimer's Disease, cell loss is not likely to be a significant contributor to functional decline in normal aging. Shifts in expression and distribution of key molecules (i.e., glutamate receptors) in otherwise intact circuits, however, do appear to be occurring in aging, and in a manner that would have profound effects on synaptic transmission in key hippocampal and neocortical circuits. These alterations in the molecular constituents of the synapse occur against a background of structural alterations of the spines and synapses that also impact function. Our interests in aging and synaptic plasticity have been expanded over the years to include research programs on the effects of stress on cortical function and plasticity, as well as the links between neuronal aging and endocrine senescence. These studies have revealed synaptic attributes in prefrontal cortex that are altered with aging yet rescued by estrogen treatment, thereby protecting against cognitive decline in aged female monkeys. We are continuing to pursue the mechanistic links between age-related decreases in estrogen levels (i.e., menopause), glutamate receptors, and cortical circuits in behaviorally and hormonally characterized aged non-human primates, with a particular focus on prefrontal cortex and related cognitive functions.

Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WG, Lou W, Rapp PR, Morrison JH. Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J. Neurosci 2010; 30(22): 7507-15.

Bloss EB, Janssen WG, McEwen BS, Morrison JH. Interactive effects of stress and aging on structural plasticity in the prefrontal cortex. J. Neurosci 2010; 30(19): 6726-31.