Optical imaging of large-scale correlated wave activity in the developing rat CNS

Correlated neuronal activity plays a fundamental role in the development of the nervous system. Using a multiple-site optical recording technique with a fast voltage-sensitive dye, we previously reported a novel form of correlated activity in the chick embryo, which showed wide propagation throughout the CNS. In this study, we report that similar wave activity is generated in the embryonic rat CNS. Electrical stimulation applied to the cervical cord evoked wave activity that traveled over a wide region of the CNS including the medulla, pons, midbrain, diencephalon, and spinal cord. Small signals were also detected from the cerebellum and part of the cerebrum. Stimulation applied to the cranial nerves such as the trigeminal and vagus nerves evoked waves with similar patterns, indicating that the wave is triggered by external sensory inputs. This wave activity was inhibited by glutamate-, acetylcholine-, GABA- and glycine-receptor antagonists in addition to gap junction blockers such as octanol and 18beta-glycyrrhetinic acid. In the immunohistochemical study, significant immunoreactivity of connexin26 and connexin32 was also observed. Wave activity detected with a voltage-sensitive dye was accompanied by a Ca(2+)-wave, indicating that it not only provides electrical synchrony but also biochemical signals associated with [Ca2+](i) elevation. These characteristics of the wave activity are similar to those of the depolarization wave reported in the chick embryo, suggesting that the large-scale depolarization wave is globally generated across different species.