Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells

Nat Commun. 2017 Jul 28;8(1):152. doi: 10.1038/s41467-017-00218-y.


Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.

Publication types

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

MeSH terms

  • Animals
  • CA3 Region, Hippocampal / growth & development
  • CA3 Region, Hippocampal / metabolism
  • Dendrites / metabolism
  • Entorhinal Cortex / metabolism
  • GABAergic Neurons / metabolism*
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Interneurons / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / metabolism*
  • Neuronal Plasticity / genetics*
  • Neurons, Afferent / metabolism*
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / metabolism
  • Thalamus / metabolism


  • Gprin1 protein, mouse
  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate