Mechanisms of Associative Learning in Young and Aging Brain
Northwestern University (Chicago, USA)
Experiments in my laboratory are focused on understanding mechanisms for alterations that occur during associative learning and how learning is affected by aging. I will give a brief review of experiments demonstrating that intrinsic excitability of CA1 hippocampal neurons is increased when animals learn a hippocampus-dependent task; that intrinsic excitability is reduced in aging animals with age-associated learning deficits; and that we can enhance learning by increasing hippocampal neuron excitability pharmacologically or with molecular genetic techniques. We also have several ongoing interrelated projects that will be highlighted. 2-photon calcium imaging combined with whole cell patch recording is being used to examine calcium transients in hippocampal CA1 neurons from young and aging rats. Interestingly, we observe that calcium transients are greatly enhanced in aged CA1 pyramidal neurons after the postburst AHP is abolished with a cholinergic agonist, carbachol, an effect not seen in young neurons. We now have the capacity to do 2-P glutamate uncaging, which will be used to examine alterations in dendritic spines with aging and after learning. Our collaborators at Rush University will then use array tomography and immunogold field emission scanning electron microscopy to determine if structural (i.e., protein composition) changes are observed in the functionally characterized spines. Experiments have begun to look at temporal lobe regions other than hippocampal CA1, where we have concentrated most of our effort in recent years. Pyramidal neurons in both Layer II and III input and layer V output neurons of lateral entorhinal cortex are being examined in brain slices from young and aging rats. Not surprisingly, these neuron populations are showing interesting functional differences upon initial examination. Finally, considerable effort has been expended to develop a behavioral preparation for doing trace eyeblink conditioning in head fixed mice. This will allow us to more readily do experiments such as reversible inactivation with DREADDS and single neuron recording studies with moveable tetrodes during learning and in memory retention in young and aging mice. These types of studies had previously been done in our laboratory exclusively with rabbits.