Laboratory of Dan Nicholson, PhD

The laboratory of Dan Nicholson, PhD, is interested in the neurobiology of cognitive aging, Alzheimer’s disease and epilepsy. We bring to bear numerous techniques to unveil the events and pathogens that ultimately lead to brain failure, including electron microscopy, patch-clamp physiology, immunofluorescence array tomography, immunoprecipitation assays and mass spectrometry.

Our work

The majority of our work utilizes animal models of cognitive aging and Alzheimer’s disease. With our colleagues, John Disterhoft, PhD, and Matt Oh, PhD, at Northwestern University, we use 2-photon glutamate uncaging and 2-photon calcium imaging of individual dendritic transients in mouse models of Alzheimer’s disease and behaviorally characterized rats, ranging in age from four to 30 months of age. In the mouse models of Alzheimer’s disease, the vast majority show learning and memory impairments by mid-life. Among aged rats (~28 months of age and older), some learn hippocampus-dependent behaviors as well as young adult rats (aged, cognitively unimpaired), whereas others show severe learning impairments (aged, cognitively impaired). We use animals models to investigate the cellular mechanisms of both Alzheimer’s disease-linked (i.e., the mouse models of Alzheimer’s disease) and non-Alzheimer’s disease-linked (i.e., the aged impaired rats) cognitive failure.

After recording synaptically evoked, individual dendritic calcium transients, we reconstruct the imaged dendrites using the super-resolution light microscopy technique array tomography and probe for ion channels and other important signaling proteins with single-dendrite, single-spine resolution. This allows us to generate single-dendrite ion channel gradients for dendrites that represent the normal range of signaling in mice and rats (i.e., similar to wildtype/young adult values), as well as those dendrites with signaling abnormalities. We therefore have multidimensional abstractions of dendrites with both normal and abnormal calcium signaling, allowing us to identify the ion channel or channels that are tied to signaling problems.

A powerful aspect of this approach is that we can use array tomography on brain tissue from human Alzheimer’s disease, mild cognitive impairment and non-cognitively impaired cases to perform the same exact experiments on neurons that have been filled iontophoretically with fluorescent dye. We can then infer how dendrites in the human brain might have signaled by comparing their multidimensional signaling interactome to those from the rat and mouse experiments.   

Using knock-in, knock-out, overexpression and gene-editing techniques, we try to repair the aberrant ion channel gradients to restore synaptic calcium signaling back to normal, ultimately hoping to repair signaling at the whole-neuron level and learning in aged animals and Alzheimer’s disease models.


We use patch-clamp physiology, serial section conventional/DAB/immunogold electron microscopy, immunofluorescence array tomography, western blots, co-immunoprecipitation and mass spectrometry.


Our studies are funded by grants from the National Institute on Aging.

Our team

  • Dan Nicholson, PhD, associate professor of neurological sciences
  • Linda Bean, PhD, postdoctoral fellow
  • Ronen Borenstein, PhD, postdoctoral fellow
  • Tim Musial, graduate student
  • Matt Russo, graduate student
  • Gelique Ayala, research assistant
  • Sheila Mullen, research assistant


Contact Us

Dan Nicholson, PhD
Phone: (312) 942-5418