To determine how long-term memories are encoded in the adult brain remains a central problem of neuroscience. Growing evidence suggests that in addition to fast activity-dependent changes in the strengths of synaptic connections between neurons mediated by LTP/LTD, structural remodeling of axons, dendrites, and spines can also occur in the mature brain, and may contribute to the consolidation of long-term memories through changes in the cortical wiring diagram on a much slower time scale. Importantly, for both "weight based" and "wiring based" modes of learning, changes in the morphological and biophysical properties of pyramidal neurons that occur with aging, disease and mental retardation could reduce the capacity of the associated brain areas to store information effectively, leading to memory deficits and/or loss of cognitive function. The goal of this collaborative project, involving coordinated experimental and computer simulation studies in normal, aged, and Ts65Dn mice, is to flesh out the causal chain that links the morphological and biophysical properties of individual pyramidal neurons to long-term memory function and dysfunction in the adult brain.
