Temporal relation between neural activity and neurite pruning on a numerical model and a microchannel device with micro electrode array.
Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period. However, the relationship among these phenomena remains unclear because it is difficult to experimentally show how the developmental shift of inhibitory transmission influences neural activities and whether the activities promote synapse elimination and neurite pruning. In this study, we modeled synapse elimination in neuronal circuits using the modified Izhikevich's model with functional shifting of GABAergic transmission. The simulation results show that synaptic pruning within a specified period like the critical period is spontaneously generated as a function of the developmentally shifting inhibitory transmission and that the specific firing rate and increasing synchronization of neural circuits are seen at the initial stage of the critical period. This temporal relationship was experimentally supported by an in vitro primary culture of rat cortical neurons in a microchannel on a multi-electrode array (MEA). The firing rate decreased remarkably between the 18-25 days in vitro (DIV), and following these changes in the firing rate, the neurite density was slightly reduced. Our simulation and experimental results suggest that decreasing neural activity due to developing inhibitory synaptic transmission could induce synapse elimination and neurite pruning at particular time such as the critical period. Additionally, these findings indicate that we can estimate the maturity level of inhibitory transmission and the critical period by measuring the firing rate and the degree of synchronization in engineered neural networks.
Department of Information Physics and Computing, The University of Tokyo, Tokyo 113-8656, Japan.
Yohei
Y
Kondo
Department of Mechano-Informatics, The University of Tokyo, Tokyo 113-8656, Japan; Research Fellow of the Japan Society for the Promotion of Science, Japan.
Yuichiro
Y
Yada
Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
Tatsuya
T
Haga
Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
Yuzo
Y
Takayama
Department of Human and Engineered Environmental Studies, The University of Tokyo, Tokyo 113-8656, Japan; Research Fellow of the Japan Society for the Promotion of Science, Japan.
Takuya
T
Isomura
Department of Precision Engineering, The University of Tokyo, Tokyo 113-8656, Japan; Department of Human and Engineered Environmental Studies, The University of Tokyo, Tokyo 113-8656, Japan.
Yasuhiko
Y
Jimbo
Department of Information Physics and Computing, The University of Tokyo, Tokyo 113-8656, Japan.
Osamu
O
Fukayama
Department of Information Physics and Computing, The University of Tokyo, Tokyo 113-8656, Japan. Electronic address: takayuki_hoshino@ipc.i.u-tokyo.ac.jp.
Takayuki
T
Hoshino
Department of Information Physics and Computing, The University of Tokyo, Tokyo 113-8656, Japan.
Kunihiko
K
Mabuchi
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D054022:Cerebrum / Q000166:cytology / Q000502:physiology; D003198:Computer Simulation; D008839:Microelectrodes; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D061251:Primary Cell Culture; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B
Critical period; Culture device; Development; Microchannel; Microelectrode array (MEA); Neurite pruning; Synapse elimination