Functional MRI Evidence for LTP-Induced Neural Network Reorganization

Abstract

The hippocampal formation is a region of the forebrain that is important for memory and spatial navigation. On the basis of a vast amount of literature, the hippocampus is linked with long-term potentiation (LTP), the increased synaptic strength following repeated stimulation of the hippocampal neurons. LTP is considered to be the experimental demonstration of Hebb's postulate on synaptic strength and learning, and it is the dominant model of an experience-dependent modification of brain circuits. Yet, despite the importance of this phenomenon for brain physiology and behavior, little is known about how experimentally measured regional synaptic modifications alter the activity of global, widespread networks. Here, we use simultaneous fMRI, microstimulation, and electrophysiology to unveil global changes in brain activity due to local hippocampal plasticity. Our findings offer the first evidence of an LTP-induced network reorganization that includes increased interhemispheric communication and recruitment of limbic and neocortical circuits after changes in synaptic strength within the hippocampus.

Functional MRI of long-term potentiation: imaging network plasticity

“…Of note, in the hippocampus, the axial organization of the cellular elements, with a rather precise alignment of dendritic shafts and somas, minimizes the cancellation of current sources from the LFP generators and facilitates the neurophysiological interpretation of the electrically evoked field potentials, such as synaptic currents reflected in the EPSP and spiking activity in the population spike. Using this preparation, we were able to unequivocally show that the EPSP slope was a precise predictor of BOLD signal amplitude, better than either the population spike or the electrical current used for stimulation [48,49]. This result has recently been confirmed in experiments combining electrophysiological recordings with hippocampal CBF measurements based on Laser-Doppler flowmetry [69].…”

“…Activations were found in the DG, CA3 and CA1 regions, subiculum, entorhinal cortex and the septum [48]. The BOLD signal amplitude was a good predictor of the underlying electrophysiological responses as measured in combined fMRI -electrophysiology experiments in the DG (see below), very stable under urethane anaesthesia and robust across animals [48,49]. These characteristics conferred a quantitative value to the BOLD signal in long-term experiments as those required to investigate the systems-level consequences of LTP.…”

“…In an attempt to link the cellular and system levels of memory consolidation, that is to relate synaptic plasticity to widespread network dynamics, we simultaneously combined fMRI and in vivo electrophysiology in rats [48] and investigated the global functional consequences of LTP [49]. In these acute experiments, urethane-anaesthetized rats are implanted in the perforant pathway (PP) and dentate gyrus (DG) with MRI-compatible stimulating and recording electrodes, respectively.…”

“…and secured in a stereotaxic device. Stimulating electrodes were implanted using standard surgical and stereotaxic procedures, as described previously [48,49]. A twisted platinum-iridium Teflon-coated bipolar electrode (200 mm diameter, 10-15 kW: A-M Systems, WA, USA) was positioned in the medial PP (from l: 0 mm anteroposterior and 4.1-4.5 mm lateral, 2.5-3 mm ventral to the dural surface) for orthodromic stimulation of the DG and the hippocampus proper [95].…”

“…LTP was induced in all experiments as previously described [49]. In short, LTP was induced by high-frequency stimulation of the PP with episodes of six trains of pulses (each train delivered at 200 Hz and lasting 40 ms, with four pulses per train and trains delivered every 10 s) repeated three times with pauses of 2 min between episodes.…”