Thivierge, J. P., Shultz, T. R., & Balaban, E. (2005). A unified model of thalamocortical axon guidance. Proceedings of the Twentieth AAAI Annual Conference (pp.3-14). Menlo Park, California: AAAI.



Thalamocortical (TC) projections project through the ventral telencephalon (VTe) to relay sensory information from the thalamus (Th) to the neocortex (NC). Information comes into the Th regionally segregated by sensory modality (vision, hearing, touch), and within each modality, by body region; the TC projections conserve the topography both by modality (sent to different brain regions [inter-area]) and body region (within each brain region [intra-area]). Initial TC projections are established by an activity-independent process that includes the gradient expression of Eph/ephrin molecules. Subsequently, an activity-dependent process working through synaptic depolarization refines the position of axons in the NC. We propose a model that combines activity-independent servomechanical guidance of TC axons and competitive mechanisms preventing spatial clustering of axons with an activity-dependent, Hebbian winner-take-all process (based on the activation of NMDA and GABA receptors) used in previous work (Thivierge & Balaban, 2005). This model governs both initial projections from the thalamus to the VTe, and subsequent movement of axons from the VTe to target regions of the NC, and reproduces the both inter-regional and intra-regional topography of TC projections. Simulations replicate experiments with ephrin-A5 knockout mice as well as cortical reorganization following focal deafferentation. The model is the first to integrate both activity-independent and activity-dependent processes to explain cortical map formation, and yields testable predictions for future experiments.


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