Summary The neocortex has a globally encompassing network structure, which for each given input constrains the possible combinations of neuronal activations across it. Hence, its network contains solutions. But in addition, the cortex has an ever-changing multidimensional internal state, causing each given input to result in a wide range of specific neuronal activations. Here we use intracellular recordings in somatosensory cortex (SI) neurons of anesthetized rats to show that remote, subthreshold intracortical electrical perturbation can impact such constraints on the responses to a set of spatiotemporal tactile input patterns. Whereas each given input pattern normally induces a wide set of preferred response states, when combined with cortical perturbation response states that did not otherwise occur were induced and consequently made other response states less likely. The findings indicate that the physiological network structure can dynamically change as the state of any given cortical region changes, thereby enabling a rich, multifactorial, perceptual capability.

BackgroundIt is still unclear to what extent the most common animal models of pain and analgesia, based on indirect measures such as nocifensive behaviours, provide valid measures of pain perception.MethodsTo address this issue, we developed a novel animal model comprising a more direct readout via chronically (>1 month) implanted multichannel electrodes (MCE) in rat primary somatosensory cortex (S1; known to be involved in pain perception in humans) and compared this readout to commonly used behavioural pain‐related measures during development of hyperalgesia. A translational method to induce hyperalgesia, UVB irradiation of the skin, was used. Localized CO 2 laser stimulation was made of twenty skin sites (20 stimulations/site/observation day) on the plantar hind paw, before and during the time period when enhanced pain perception is reported in humans after UVB irradiation.ResultsWe demonstrate a 2–10 fold significant enhancement of cortical activity evoked from both irradiated and adjacent skin and a time course that corresponds to previously reported enhancement of pain magnitude during development of primary and secondary hyperalgesia in humans. In contrast, withdrawal reflexes were only significantly potentiated from the irradiated skin area and this potentiation was significantly delayed as compared to activity in S1.ConclusionsThe present findings provide direct evidence that chronic recordings in S1 in awake animals can offer a powerful, and much sought for, translational model of the perception of pain magnitude during hyperalgesia.What does this study add? In a novel animal model, chronic recordings of nociceptive activity in primary somatosensory cortex (S1) in awake freely moving rats are compared to behavioural readouts during UVB‐induced hyperalgesia. Evoked activity in rat S1 replicates altered pain perception in humans during development of hyperalgesia, but withdrawal reflexes do not.

Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved.