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Title: Synaptic integration in layer 5 cortical pyramidal cells and the role of background synaptic input explored with compartmental modeling
Author: Farinella, M.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Pyramidal cells are the principal excitatory neurons in the cerebral cortex and those in layer 5 (L5) form its primary output. Tufted L5 pyramidal cells present a complex morphology, with non-uniform distributions of active membrane conductances. Their dendritic tree receives thousands of synaptic inputs from local circuits as well as long range inputs from other cortical regions and thalamic nuclei. Hence, the timing of their synaptic inputs are likely to span a wide range of temporal scales, raising the question of how an individual L5 pyramidal cell combines and transforms such temporally and spatially diverse signals. The integrative properties of pyramidal neurons have been extensively studied in vitro and several models have been suggested for the computations performed by these cells. However, cortical pyramidal cells in vivo are constantly bombarded by asynchronous synaptic input, re ecting the activity of the network in which they are embedded. Little is known about how the resulting background activity interacts with nonlinear dendritic properties. I have used experimentally-constrained models of L5 pyramidal neurons to explore synaptic integration under a range of di erent conditions including those measured in vivo. The major result from this study is that background synaptic activity can profoundly alter the integrative properties of pyramidal cells, by activating a distributed NMDA receptor conductance. This distributed nonlinear conductance lowers the threshold for dendritic spikes generation, extends the spikes duration and increases the probability of additional regenerative events occurring in neighbouring branches. Simulations with mixed excitatory/inhibitory background also suggest that dendritic inhibition may be speci cally tuned to regulate this powerful re-generative mechanism. My results suggest a new role for NMDA receptors. During the network activity experienced by pyramidal neurons in vivo, the distributed NMDA conductance may enable pyramidal cells to integrate synaptic input over extended spatio-temporal scales.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available