Targeted cortical reorganization using optogenetics in non-human primates

Elife. 2018 May 29:7:e31034. doi: 10.7554/eLife.31034.

Abstract

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation.

Keywords: functional connectivity; neural stimulation; neuromodulation; neuroscience; non-human primates; optogenetics; plasticity; rhesus macaque.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Waves / physiology
  • Connectome / methods
  • Dependovirus / genetics
  • Dependovirus / metabolism
  • Electrodes, Implanted
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Macaca mulatta
  • Male
  • Motor Cortex / anatomy & histology
  • Motor Cortex / cytology
  • Motor Cortex / physiology*
  • Nerve Net / anatomy & histology
  • Nerve Net / cytology
  • Nerve Net / physiology*
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Opsins / genetics
  • Opsins / metabolism
  • Optogenetics / methods
  • Somatosensory Cortex / anatomy & histology
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / physiology*

Substances

  • Opsins

Grants and funding

This research was partially funded by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0043, issued by the Army Research Office contracting office in support of DARPA'S SUBNETS program. The views, opinions, and/or findings expressed are those of the author(s) and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.