Layer III neurons control synchronized waves in the immature cerebral cortex

J Neurosci. 2013 Jan 16;33(3):987-1001. doi: 10.1523/JNEUROSCI.2522-12.2013.


Correlated spiking activity prevails in immature cortical networks and is believed to contribute to neuronal circuit maturation; however, its spatiotemporal organization is not fully understood. Using wide-field calcium imaging from acute whole-brain slices of rat pups on postnatal days 1-6, we found that correlated spikes were initiated in the anterior part of the lateral entorhinal cortex and propagated anteriorly to the frontal cortex and posteriorly to the medial entorhinal cortex, forming traveling waves that engaged almost the entire cortex. The waves were blocked by ionotropic glutamatergic receptor antagonists but not by GABAergic receptor antagonists. During wave events, glutamatergic and GABAergic synaptic inputs were balanced and induced UP state-like depolarization. Magnified monitoring with cellular resolution revealed that the layer III neurons were first activated when the waves were initiated. Consistent with this finding, layer III contained a larger number of neurons that were autonomously active, even under a blockade of synaptic transmission. During wave propagation, the layer III neurons constituted a leading front of the wave. The waves did not enter the parasubiculum; however, in some cases, they were reflected at the parasubicular border and propagated back in the opposite direction. During this reflection process, the layer III neurons in the medial entorhinal cortex maintained persistent activity. Thus, our data emphasize the role of layer III in early network behaviors and provide insight into the circuit mechanisms through which cerebral cortical networks maturate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Brain Waves / drug effects
  • Brain Waves / physiology*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Carbenoxolone / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Rats
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Excitatory Amino Acid Antagonists
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Carbenoxolone