Dr. David Jaffe
Research in my laboratory focuses on the hippocampal formation; a brain region important for certain aspects of learning and memory. It is also one of the first brain structures affected by Alzheimer's disease and and medial temporal lobe epilepsy arises in the hippocampus, among other brain structures.
Our major area of interest is the CA3 region of the hippocampus. This subregion is where information from two regions outside the hippocampus, the dentate gyrus and the entorhinal cortex, converge. In addition, this area is also characterized by strong recurrent feedback between CA3 pyramidal neurons forming what is thought to be an autoassociative network. Artificial neural networks composed of such circuits perform pattern completion. Under pathalogical conditions, this circuity is what makes area CA3 highly susceptible to epilepsy.
Current work in the laboratory focuses on two questions. First, what are the input/output characteristics of CA3 pyramidal neurons? We are interested in how the morphology and distribution of ion channels in these cells interact to process, encode, and retrieve synaptically-based information. Understanding how these cells integrate synaptic information is important for understanding the functional role of this network during normal circumstances and under pathophysiological conditions, for example in the case of epilepsy. Our second question concerns how the properties of neurons and synapses within area CA3 change in aged animals. It is well known that aged animals are cognitively impaired and this correlates with a number of cellular changes that occur with senescence. The laboratory is testing whether some of these changes might actually be compensatory. That is, in response to pathophysiological changes that occur with age, such as the loss of receptors associated with synaptic, certain changes in excitability or synaptic inhibition may enhance functional aspects of the network as it ages.
Jaffe, D.B., Wang, B., and Brenner, R. Shaping of action potentials by type I and type II large-conductance Ca2+-activated K+ channels, Neurosci., 192:205-218, 2011.
Migliore, M., Jaffe, D.B., Barrionuevo, G., and Ascoli, G., “CA3 pyramidal neuron firing patterns revisited: higher-order analysis of parameter space”, In: Hippocampal Microcircuits: A Computational Modeller's Resource Book, Cutsuridis, Graham, Cobb, and Vida (eds.), 2010.
Hemond, P., Migliore, M., Ascoli, G., and Jaffe, D.B., The membrane response of hippocampal CA3b pyramidal neurons near rest: heterogeneity of passive properties and the contribution of hyperpolarization-activated currents, Neurosci., 160:359-370, 2009.
Hemond, P., Epstein, D., Boley, A., Migliore, M., Ascoli, G., and Jaffe, D.B., Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b, Hippocampus 18:411-424, 2008.
Dikkes, P, Jaffe, D., Chao, C., Hemond, P., Yoon, K., Guo, W. Lopez, M.F. Igf2 knockout mice are resistant to kainic acid-induced seizures and neurodegeneration. Brain Res., 1175:85-90, 2007.
Zaika, O., Tolstykh, G.P., Jaffe, D.B., and Shapiro, M.S., IP3-mediated Ca2+ signals direct purinergic P2Y-receptor regulation of neuronal ion channels, J. Neurosci., 27:8914-8926, 2007.