Biophysics, Learning and Memory Mechanisms in the Young and Aged Brain

Professor Jackie Schiller

How memories are encoded in the mature brain, and how they are changed in the aged brain and during pathological brain conditions, remain among the biggest problems to be solved. It is widely believed that acquisition of memories involve changes at the cellular and circuit level. Increasing evidence points to structural and physiological remodeling of dendrites and spines as well as biophysical properties of pyramidal neurons in the mature brain, which are the principle neurons in the cortical tissue.

In my lab, we are interested in unraveling the functional changes that occur in dendrites and spines, which are the main sites where information is processed. One of the major questions we are concentrating on is how the single pyramidal neuron processes its vast synaptic information. Although we have made some progress towards understanding the integrative behavior of pyramidal neurons in normal young animals, virtually nothing is known concerning the changes in morphology, physiology and biophysics that are associated with aging and pathological conditions such as Alzheimer’s disease.Jackie Schiller

Using combined advanced imaging, electrophysiology, molecular and anatomical methods we are capable of following the biophysical and functional changes with unprecedented high resolution in dendrites and spines of pyramidal neurons at the living animal as well as in slice preparation.

We plan to implement these advanced technologies to normal aging and animal models of Alzheimer’s disease. We hypothesize that the initial changes that underlie cognitive decline are impaired nonlinear dendritic amplification and compartmentalization of dendrites. We plan to test these possibilities in both normal aging and transgenic mice models of AD. The experiments will be performed in regions of the brain (such as the prefrontal cortex and hippocampus) that are implicated in the formation and consolidation of “working memories” and long-lasting memories. The data will be compared with primary somatosensory regions in the brain to better understand how single neuron changes in the different conditions bear upon the mechanisms underlying memory formation in the mature, aged and pathological brain.