The hippocampus is the cradle of cognition—a brain structure critically involved in the formation, organization, and storage of new memories. To understand how hippocampal circuits contribute to these processes, we must elucidate how its neurons integrate and transmit information and how they are influenced by modulatory systems that fluctuate with behavior. The principal outputs of the hippocampus are pyramidal neurons that project to numerous cortical and subcortical targets. For example, some pyramidal cells in the subiculum project to medial entorhinal cortex, which processes spatial information, while others project to lateral entorhinal cortex, which processes non-spatial information. Do these pyramidal cells process information in similar ways, or are there multiple types of pyramidal cells that independently process information in parallel?
My dissertation research employed electrophysiological and morphological analyses to address this question in order to further our understanding of how the hippocampus processes information on a cellular level. Using unbiased cluster analysis, I show that throughout CA1 and subiculum, there are two separate classes of pyramidal cells with distinct electrophysiological properties and dendritic morphologies, implying that the two cell types process synaptic inputs differently. Combined with previous work, these findings suggest that the two cell types in the subiculum are biased toward carrying separate types of information, thus supporting cell-type-specific parallel processing in the hippocampus. I show further that the two pyramidal cell types are differentially modulated by metabotropic glutamate and acetylcholine receptors: activation of receptor subtypes that increased bursting in one class decreased it in the other. Finally, I demonstrate that the two cell types differentially engage brain-derived neurotrophic factor and other signaling cascades to bidirectionally modulate ion channel function, resulting in long-lasting changes in the firing properties of these cells. This bidirectional countermodulation enables differential emphasis of spatial and non-spatial information leaving the hippocampus. More generally, the principle of differential modulation of multiple cell types, which is well established in other systems, may also provide a substrate for behaviorally relevant control of parallel information streams in the hippocampus.
|Commitee:||Dombeck, Dan, McLean, Dave, Surmeier, Jim|
|Department:||Neuroscience Institute Graduate Program|
|School Location:||United States -- Illinois|
|Source:||DAI-B 74/05(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Cellular biology, Physiology|
|Keywords:||Ca1, Cell types, Hippocampus, Neuromodulation, Plasticity, Pyramidal neurons, Synergy|
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