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Abstract

Repetitive stimulation of hippocampal neurons induce a fast and prolonged increase in local synaptic strength, which is known as LTP (long-term potentiation). LTP is currently considered as being the cellular model of associative learning and memory. Despite the relevance of such phenomenon in the healthy and diseased brain, and all valuable information gained in the study of its cellular and molecular mechanisms, little is known about its role in whole-brain functional connectivity. The lack of a better understanding of the context-dependent network organization most likely reflects the fact that most current methodologies are not really suited for the study of mass action. In an attempt to overcome this limitation, we previously combined electrophysiological techniques and electrical microstimulation of the rat perforant path with functional magnetic resonance imaging (fMRI) (Canals et al. 2008, in press) and showed that the fMRI signal (BOLD) in this model is a good surrogate of the neuronal activity as measured electrophysiologically. Here, we investigate the functional patterns produced as a result of long-term potentiation of synaptic transmission in the rat hippocampus. FMRI maps of the entire brain were obtained before, during and after the induction of LTP, demonstrating changes in functional connectivity due to synaptic potentiation. Furthermore, our results demonstrate that the magnitude of the potentiation is heterogeneously distributed across different hippocampal areas, and that interhemispheric communication is also potentiated after LTP induction. The present model (BOLD-LTP) represents the first demonstration of synaptic plasticity using fMRI and will allow us to further study the information transfer between the hippocampus, the cerebral cortex and subcortical structures, providing new data for the understanding of memory and learning processes.