Nociception-Induced Spatial and Temporal Plasticity of Synaptic Connection and Function in the Hippocampal Formation of Rats: a Multi-Electrode Array Recording

Abstract

BackgroundPain 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, we studied spatiotemporal plasticity of synaptic connection and function in the hippocampal formation (HF) in response to persistent nociception.ResultsOn the hippocampal slices of rats which had suffered from persistent nociception for 2 h by receiving subcutaneous bee venom (BV) or formalin injection into one hand paw, multisite recordings were performed by an 8 × 8 multi-electrode array probe. 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, BV- or formalin-induced persistent pain significantly increased the number of detectable fEPSP in both DG and CA1 area, implicating enlargement of the synaptic connection size by the injury or acute inflammation. Moreover, the input-output function of synaptic efficacy was shown to be distinctly enhanced by the injury with the stimulus-response curve being moved leftward compared to the control. For the temporal plasticity, long-term potentiation produced by theta burst stimulation (TBS) conditioning was also remarkably enhanced by pain. Moreover, it is strikingly noted that the shape of fEPSP waveform was drastically deformed or split by a TBS conditioning 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, confirmed by the 2-dimentional current source density imaging, were found to be highly correlated with peripheral persistent nociception since pre-blockade of nociceptive impulses could eliminate all of them. Finally, the initial pharmacological investigation showed that AMPA/KA glutamate receptors might play more important roles in mediation of pain-associated spatiotemporal plasticity than NMDA receptors.ConclusionPeripheral 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 fEPSP at local circuit level and, increased synaptic efficacy at cellular level. In addition, the multi-synaptic model established in the pres...

Use of multi-electrode array recordings in studies of network synaptic plasticity in both time and space

“…As expected, the negative-going LFPs evoked by PP stimulation at the site (asterisk, electrode #29, Fig. 3A) were mainly confined to the dendritic distribution areas of both granular and pyramidal neurons in the normal or saline control state [31] . The spread of the PP-evoked depolarization was clearly shown by 2-dimensional current source density (2D-CSD) imaging (Fig.…”

“…To summarize, the though the latter at 100 µmol/L also significantly reduced the whole network response (see Fig. 5 of Zhao et al [31] ).…”

“…2), we stably recorded simultaneous responses across both dentate gyrus (DG) and CA1 regions after electrical stimulation of the perforant pathway (PP) (Fig. 3) [31] . Because the PP fibers project mainly to the molecular layer of the DG and molecular and radiatum layers of CA1 where the dendritic trees of granular neurons and apical dendrites of pyramidal neurons are localized (Fig.…”

“…The spread of the PP-evoked depolarization was clearly shown by 2-dimensional current source density (2D-CSD) imaging (Fig. 4A) [31] . The current sink As shown in Fig.…”

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

“…Wei, Xu, Qu, Milbrandt, & Zhuo (2000) first recorded a hippocampal reaction to peripheral noxious stimulations in adult rats. Zhao reported that in a bee venom‐induced persistent pain animal model, hippocampus LTP was remarkably enhanced (Zhao et al., 2009). In this study, we observed that LTP induced by HFS in the hippocampus CA1 region significantly increased in IBS‐like rats, which is in accordance with our previous data (Chen et al., 2014).…”