The mediodorsal thalamus drives feedforward inhibition in the anterior cingulate cortex via parvalbumin interneurons

J Neurosci. 2015 Apr 8;35(14):5743-53. doi: 10.1523/JNEUROSCI.4565-14.2015.


Although the medial prefrontal cortex (mPFC) is classically defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD), the nature of information transfer between MD and mPFC is poorly understood. In sensory thalamocortical pathways, thalamic recruitment of feedforward inhibition mediated by fast-spiking, putative parvalbumin-expressing (PV) interneurons is a key feature that enables cortical neurons to represent sensory stimuli with high temporal fidelity. Whether a similar circuit mechanism is in place for the projection from the MD (a higher-order thalamic nucleus that does not receive direct input from the periphery) to the mPFC is unknown. Here we show in mice that inputs from the MD drive disynaptic feedforward inhibition in the dorsal anterior cingulate cortex (dACC) subregion of the mPFC. In particular, we demonstrate that axons arising from MD neurons directly synapse onto and excite PV interneurons that in turn mediate feedforward inhibition of pyramidal neurons in layer 3 of the dACC. This feedforward inhibition in the dACC limits the time window during which pyramidal neurons integrate excitatory synaptic inputs and fire action potentials, but in a manner that allows for greater flexibility than in sensory cortex. These findings provide a foundation for understanding the role of MD-PFC circuit function in cognition.

Keywords: anterior cingulate cortex; feedforward inhibition; medial prefrontal cortex; mediodorsal thalamus; parvalbumin interneuron.

Publication types

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

MeSH terms

  • Afferent Pathways / physiology*
  • Animals
  • Channelrhodopsins
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dependovirus / genetics
  • Excitatory Amino Acid Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Gyrus Cinguli / cytology*
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mediodorsal Thalamic Nucleus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / physiology*
  • Neurons / physiology*
  • Parvalbumins / genetics
  • Parvalbumins / metabolism*
  • Picrotoxin / pharmacology
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Synaptic Potentials / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transduction, Genetic


  • Channelrhodopsins
  • DNA-Binding Proteins
  • Excitatory Amino Acid Agonists
  • GABA Antagonists
  • Grhl3 protein, mouse
  • Gt(ROSA)26Sor non-coding RNA, mouse
  • Luminescent Proteins
  • Parvalbumins
  • RNA, Untranslated
  • Transcription Factors
  • Picrotoxin