RESUMEN
The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain. Using repetitive distension of the colon and rectum (rCRD) as a sensitization paradigm, we have identified that the spontaneous firing rates of ACC neurons and the CRD-stimulated neuronal firings were increased after repetitive visceral noxious stimulation. This correlates with increases in visceral pain responses (visceromotor responses, VMRs). Two multichannel arrays of electrodes were implanted in the MT and ACC. Recordings were performed in free-moving rats before and after repeated CRD treatment. Power spectral density analysis showed that the local field potential (LFP) recorded in the ACC displayed increases in theta band power (4-10 Hz) that were modulated by rCRD. Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions. In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain.
Asunto(s)
Giro del Cíngulo/patología , Neuronas/fisiología , Tálamo/fisiopatología , Ritmo Teta/fisiología , Dolor Visceral/patología , Potenciales de Acción/fisiología , Animales , Relojes Biológicos/fisiología , Colon/inervación , Modelos Animales de Enfermedad , Estimulación Eléctrica , Masculino , Técnicas de Placa-Clamp , Análisis de Componente Principal , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Construction and application of a neural prosthesis device that enhances existing and replaces lost memory capacity in humans is the focus of research described here in rodents. A unique approach for the analysis and application of neural population firing has been developed to decipher the pattern in which information is successfully encoded by the hippocampus where mnemonic accuracy is critical. A nonlinear dynamic multi-input multi-output (MIMO) model is utilized to extract memory relevant firing patterns in CA3 and CA1 and to predict online what the consequences of the encoded firing patterns reflect for subsequent information retrieval for successful performance of delayed-nonmatch-to-sample (DNMS) memory task in rodents. The MIMO model has been tested successfully in a number of different contexts, each of which produced improved performance by a) utilizing online predicted codes to regulate task difficulty, b) employing electrical stimulation of CA1 output areas in the same pattern as successful cell firing, c) employing electrical stimulation to recover cell firing compromised by pharmacological agents and d) transferring and improving performance in naïve animals using the same stimulation patterns that are effective in fully trained animals. The results in rodents formed the basis for extension of the MIMO model to nonhuman primates in the same type of memory task that is now being tested in the last step prior to its application in humans.