Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption

Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2106378118. doi: 10.1073/pnas.2106378118.

Abstract

Complex body movements require complex dynamics and coordination among neurons in motor cortex. Conversely, a long-standing theoretical notion supposes that if many neurons in motor cortex become excessively synchronized, they may lack the necessary complexity for healthy motor coding. However, direct experimental support for this idea is rare and underlying mechanisms are unclear. Here we recorded three-dimensional body movements and spiking activity of many single neurons in motor cortex of rats with enhanced synaptic inhibition and a transgenic rat model of Rett syndrome (RTT). For both cases, we found a collapse of complexity in the motor system. Reduced complexity was apparent in lower-dimensional, stereotyped brain-body interactions, neural synchrony, and simpler behavior. Our results demonstrate how imbalanced inhibition can cause excessive synchrony among movement-related neurons and, consequently, a stereotyped motor code. Excessive inhibition and synchrony may underlie abnormal motor function in RTT.

Keywords: Rett syndrome; body movement; inhibition; motor cortex; synchrony.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Animals
  • Brain / physiopathology*
  • Disease Models, Animal
  • Electrophysiological Phenomena
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Methyl-CpG-Binding Protein 2 / deficiency
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Methyl-CpG-Binding Protein 2 / physiology*
  • Models, Neurological
  • Motor Activity / genetics*
  • Motor Activity / physiology*
  • Motor Cortex / physiopathology
  • Motor Neurons / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Rett Syndrome / genetics*
  • Rett Syndrome / physiopathology*
  • Stereotyped Behavior / physiology

Substances

  • MECP2 protein, human
  • Mecp2 protein, rat
  • Methyl-CpG-Binding Protein 2

Associated data

  • figshare/10.6084/m9.figshare.16559976