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Temporal relation between neural activity and neurite pruning on a numerical model and a microchannel device with

Yohei Kondo1, Yuichiro Yada2, Tatsuya Haga3

  • 1Department of Information Physics and Computing, The University of Tokyo, Tokyo 113-8656, Japan.

Biochemical and Biophysical Research Communications
|March 22, 2017
PubMed
Summary

Developing inhibitory transmission in the brain regulates neural activity, leading to synapse elimination and neurite pruning during critical periods. This process is crucial for forming functional neuronal circuits.

Keywords:
Critical periodCulture deviceDevelopmentMicrochannelMicroelectrode array (MEA)Neurite pruningSynapse elimination

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Area of Science:

  • Neuroscience
  • Computational Neuroscience
  • Developmental Neuroscience

Background:

  • Synapse elimination and neurite pruning are vital for neuronal circuit formation, occurring during a critical period dependent on neural activity.
  • The developmental shift in GABA inhibitory transmission's action is hypothesized to underlie this critical period's temporal specificity.
  • The precise relationship between inhibitory transmission shifts, neural activity, and regressive events remains unclear.

Purpose of the Study:

  • To model synapse elimination in neuronal circuits incorporating a developmentally shifting GABAergic transmission.
  • To investigate how shifts in inhibitory transmission influence neural activity and promote synapse elimination and neurite pruning.
  • To experimentally validate simulation findings using in vitro neuronal cultures.

Main Methods:

  • Utilized a modified Izhikevich's model to simulate neuronal circuits with functional shifting of GABAergic transmission.
  • Analyzed simulation outputs for spontaneous synaptic pruning, firing rates, and neural synchronization.
  • Employed in vitro primary cultures of rat cortical neurons on a multi-electrode array (MEA) for experimental validation.

Main Results:

  • Simulations demonstrated that synaptic pruning occurs within a specific period, driven by developmentally shifting inhibitory transmission.
  • The model predicted specific firing rates and increased synchronization at the onset of the critical period.
  • Experimental results showed decreased firing rates (18-25 days in vitro) followed by slight neurite density reduction, supporting simulation findings.

Conclusions:

  • Decreasing neural activity, influenced by developing inhibitory synaptic transmission, can induce synapse elimination and neurite pruning during critical periods.
  • The study establishes a temporal link between inhibitory transmission development, neural activity dynamics, and structural remodeling.
  • Measuring firing rate and synchronization in engineered networks can potentially estimate inhibitory transmission maturity and critical period timing.