Steven A. Siegelbaum, Ph.D.Chair of Neuroscience, and Professor of Pharmacology
Investigator, Howard Hughes Medical Institute, Member, The Kavli Institute for Brain Science
Kolb Annex, 6th Floor
Tel +1 212-543-5246
Area of Research
Biophysics/Ion Channels, Synapses & Circuits
Function of voltage-gated ion channels in dendritic integration of synaptic signals during learning and memory. Regulation of channel trafficking and function in neuronal dendrites. Genetic approaches to the study of information processing through circuit
We use electrophysiological recordings from brain slices, two-photon light microscopic imaging, and molecular/genetic approaches to study the mechanisms by which neuronal dendrites actively process synaptic signals to regulate information flow through neuronal circuits. One area of interest concerns the role of the HCN1 hyperpolarization-activated cation channels in regulating dendritic integration in hippocampal CA1 pyramidal neurons. Surprisingly, HCN1 knockout mice show an enhancement in hippocampal-dependent spatial learning and memory. This is associated with an enhancement of dendritic integration and in long-term potentiation of those excitatory inputs targeted to the distal tips of the dendrites, the site of greatest HCN1 expression. Now we are examining how these distal synapses contribute to learning and memory. We found that these inputs may act as training signals, inducing a novel form of synaptic plasticity at synapses that terminate on more proximal regions of the dendritic tree. We are exploring the molecular basis of this form of plasticity and designing experiments to assess its role in learning and memory.
Tsay, D., Dudman, J.T. and Siegelbaum SA. (2007). HCN1 channels constrain synaptically evoked Ca(2+) spikes in distal dendrites of CA1 pyramidal neurons. Neuron 56:1076-1089.