Publications by authors named "Harrison J Ramsay"

Tools for visualizing and manipulating protein dynamics in living cells are critical for understanding cellular function. Here we leverage recently available monoclonal antibody sequences to generate a set of affinity tags for labeling and manipulating AMPA-type glutamate receptors (AMPARs), which mediate nearly all excitatory neurotransmission in the central nervous system. These antibodies can be produced from heterologous cells for exogenous labeling applications or directly expressed in living neurons as intrabodies, where they bind their epitopes in the endoplasmic reticulum and co-traffic to the cell surface for visualization with cell impermeant fluorescent dyes.

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Postsynaptic neurotransmitter receptors and their associated scaffolding proteins assemble into discrete, nanometer-scale subsynaptic domains (SSDs) within the postsynaptic membrane at both excitatory and inhibitory synapses. Intriguingly, postsynaptic receptor SSDs are mirrored by closely apposed presynaptic active zones. These trans-synaptic molecular assemblies are thought to be important for efficient neurotransmission because they concentrate postsynaptic receptors near sites of presynaptic neurotransmitter release.

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Secreted amyloid-β (Aβ) peptide forms neurotoxic oligomeric assemblies thought to cause synaptic deficits associated with Alzheimer's disease (AD). Soluble Aβ oligomers (Aβo) directly bind to neurons with high affinity and block plasticity mechanisms related to learning and memory, trigger loss of excitatory synapses and eventually cause cell death. While Aβo toxicity has been intensely investigated, it remains unclear precisely where Aβo initially binds to the surface of neurons and whether sites of binding relate to synaptic deficits.

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Aging involves a decline in neural function that contributes to cognitive impairment and disease. However, the mechanisms underlying the transition from a young-and-healthy to aged-and-dysfunctional brain are not well understood. Here, we report breakdown of the vascular blood-brain barrier (BBB) in aging humans and rodents, which begins as early as middle age and progresses to the end of the life span.

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