The subiculum is a crossroads of hippocampal and parahippocampal projections, and the major output structure of the region. The subiculum is a region of intermediate complexity between CA3, a region with a single layer of interconnected pyramidal neurons, and the 6-layered parahippocampal and neocortices, regions with multiple principal cells connected via intralaminar and interlaminar circuits. Physiological investigation and modeling of CA3 has provided many insights into basic epileptogenesis. The greater complexity and location of subiculum makes it a logical next structure for study of additional mechanisms of seizure origin and spread. We propose to evaluate connectivity and activity spread in subiculum by combining anatomical and physiological methods with computer modeling. We will focus on network dynamics, using existing results to define voltage-sensitive and synaptic channels for the cell models. The research will proceed via the following specific aims:
AIM 1 : Measure subthreshold and suprathreshold properties of pyramidal and interneurons of subiculum and relate these to firing patterns and dendritic morphology.
AIM 2 : Develop combined and hybrid neural network software tools and fitting algorithms to match models to physiology.
AIM 3 : Define input/output relations for subicular pyramidal cells to excitatory and inhibitory connections.
AIM 4 : Explore spread of activity with multi-electrode recordings and match patterns of spread to the computer network model. Our research will allow us to begin to define and classify patterns of activity initiation, filtering, sustention and boosting in cortical circuits. This will set the stage for use of the subiculum slice and subiculum computer model as an epilepsy model.
| Fenton, Andre A; Lytton, William W; Barry, Jeremy M et al. (2010) Attention-like modulation of hippocampus place cell discharge. J Neurosci 30:4613-25 |
| Lytton, William W (2008) Computer modelling of epilepsy. Nat Rev Neurosci 9:626-37 |
| Fenton, Andre A; Kao, Hsin-Yi; Neymotin, Samuel A et al. (2008) Unmasking the CA1 ensemble place code by exposures to small and large environments: more place cells and multiple, irregularly arranged, and expanded place fields in the larger space. J Neurosci 28:11250-62 |
| Lytton, William W; Neymotin, Samuel A; Hines, Michael L (2008) The virtual slice setup. J Neurosci Methods 171:309-15 |
| Lytton, William W; Omurtag, Ahmet; Neymotin, Samuel A et al. (2008) Just-in-time connectivity for large spiking networks. Neural Comput 20:2745-56 |
| Orman, R; Von Gizycki, H; Lytton, W W et al. (2008) Local axon collaterals of area CA1 support spread of epileptiform discharges within CA1, but propagation is unidirectional. Hippocampus 18:1021-33 |
| Lytton, William W; Orman, Rena; Stewart, Mark (2008) Broadening of activity with flow across neural structures. Perception 37:401-7 |
| Lytton, William W; Omurtag, Ahmet (2007) Tonic-clonic transitions in computer simulation. J Clin Neurophysiol 24:175-81 |
| Lytton, William W; Stewart, Mark (2007) Data mining through simulation. Methods Mol Biol 401:155-66 |
| Migliore, M; Cannia, C; Lytton, W W et al. (2006) Parallel network simulations with NEURON. J Comput Neurosci 21:119-29 |
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