NOCICEPTION-INDUCED SPATIOTEMPORAL PLASTICITY OF SYNAPTIC CONNECTIONS
AND FUNCTIONS IN THE HIPPOCAMPAL FORMATION OF RATS
JUN CHEN
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,
Pain is known to be processed by a complex neural network (neuromatrix) in the brain. It is hypothesized that under pathological state, persistent or chronic pain can affect various higher brain functions through ascending pathways, leading to co-morbidities or mental disability of pain. However, so far the influences of pathological pain on the higher brain functions are less clear and this may hinder the advances in pain therapy. In the current study, by virtue of a well-developed multi-electrode array technique, we established an in vitro ‘neural network’ model for studying spatiotemporal plasticity of synaptic connection and function in the hippocampal formation (HF) in response to persistent nociception. The waveform of the field excitatory postsynaptic potential (fEPSP), induced by perforant path electrical stimulation and pharmacologically identified as being activity-dependent and mediated by ionotropic glutamate receptors, was consistently positive-going in the dentate gyrus (DG), while that in the CA1 was negative-going in shape in naïve and saline control groups. For the spatial characteristics of synaptic plasticity, persistent pain significantly increased the number of detectable fEPSP in both DG and CA1 area at the network level and distinctly enhanced the input-output function of individual synaptic efficacy at the cellular level. For the temporal plasticity, long-term potentiation produced by theta burst stimulation conditioning was also remarkably enhanced by pain. Moreover, it is strikingly noted that the shape of fEPSP waveform was drastically deformed or split by the conditioning stimulus under the condition of persistent nociception, while that in naïve or saline control state was not affected. All these changes in synaptic connection and function were further confirmed by the 2-dimentional current source density imaging. As an initial step in dissecting the mechanisms underlying this phenomenon, we performed infrared differential interference contrast patch clamp recordings on acutely prepared hippocampal slices and found that persistent pain could produce abnormal changes in the intrinsic synaptic properties of the HF, reflected as varied alterations in different parameters of miniature excitatory and inhibitory postsynaptic currents. These results indicate that peripheral persistent nociception produces great impact upon the higher brain structures that lead to not only temporal plasticity, but also spatial plasticity of synaptic connection and function in the HF. The spatial plasticity of synaptic activities is more complex than the temporal plasticity, comprising of enlargement of synaptic connection size at network level, deformed fEPSPs at local circuit level and, increased synaptic efficacy at cellular level.