Synaptic circuit organization of motor corticothalamic neurons

J Neurosci. 2015 Feb 4;35(5):2293-307. doi: 10.1523/JNEUROSCI.4023-14.2015.


Corticothalamic (CT) neurons in layer 6 constitute a large but enigmatic class of cortical projection neurons. How they are integrated into intracortical and thalamo-cortico-thalamic circuits is incompletely understood, especially outside of sensory cortex. Here, we investigated CT circuits in mouse forelimb motor cortex (M1) using multiple circuit-analysis methods. Stimulating and recording from CT, intratelencephalic (IT), and pyramidal tract (PT) projection neurons, we found strong CT↔ CT and CT↔ IT connections; however, CT→IT connections were limited to IT neurons in layer 6, not 5B. There was strikingly little CT↔ PT excitatory connectivity. Disynaptic inhibition systematically accompanied excitation in these pathways, scaling with the amplitude of excitation according to both presynaptic (class-specific) and postsynaptic (cell-by-cell) factors. In particular, CT neurons evoked proportionally more inhibition relative to excitation (I/E ratio) than IT neurons. Furthermore, the amplitude of inhibition was tuned to match the amount of excitation at the level of individual neurons; in the extreme, neurons receiving no excitation received no inhibition either. Extending these studies to dissect the connectivity between cortex and thalamus, we found that M1-CT neurons and thalamocortical neurons in the ventrolateral (VL) nucleus were remarkably unconnected in either direction. Instead, VL axons in the cortex excited both IT and PT neurons, and CT axons in the thalamus excited other thalamic neurons, including those in the posterior nucleus, which additionally received PT excitation. These findings, which contrast in several ways with previous observations in sensory areas, illuminate the basic circuit organization of CT neurons within M1 and between M1 and thalamus.

Keywords: VA/VL; cortex; corticothalamic; disynaptic inhibition; layer 6; projection neuron.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Animals
  • Excitatory Postsynaptic Potentials
  • Female
  • Inhibitory Postsynaptic Potentials
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Cortex / cytology
  • Motor Cortex / physiology*
  • Nerve Net / cytology
  • Nerve Net / physiology*
  • Neurons / physiology
  • Pyramidal Tracts / physiology*
  • Synapses / physiology*
  • Telencephalon / cytology
  • Telencephalon / physiology
  • Thalamus / cytology
  • Thalamus / physiology*