Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus

Brain Struct Funct. 2015 Mar;220(2):919-40. doi: 10.1007/s00429-013-0692-6. Epub 2014 Jan 10.


Three functionally different populations of perisomatic interneurons establish GABAergic synapses on hippocampal pyramidal cells: parvalbumin (PV)-containing basket cells, type 1 cannabinoid receptor (CB1)-positive basket cells both of which target somata, and PV-positive axo-axonic cells that innervate axon initial segments. Using electron microscopic reconstructions, we estimated that a pyramidal cell body receives synapses from about 60 and 140 synaptic terminals in the CA1 and CA3 area, respectively. About 60 % of these terminals were PV positive, whereas 35-40 % of them were CB1 positive. Only about 1 % (CA1) and 4 % (CA3) of the somatic boutons were negative for both markers. Using fluorescent labeling, we showed that most of the CB1-positive terminals expressed vesicular glutamate transporter 3. Reconstruction of somatic boutons revealed that although their volumes are similar, CB1-positive boutons are more flat and the total volume of their mitochondria was smaller than that of PV-positive boutons. Both types of boutons contain dense-core vesicles and frequently formed multiple release sites on their targets and innervated an additional soma or dendrite as well. PV-positive boutons possessed small, macular synapses; whereas the total synaptic area of CB1-positive boutons was larger and formed multiple irregular-shaped synapses. Axo-axonic boutons were smaller than somatic boutons, had only one synapse and their ultrastructural parameters were closer to those of PV-positive somatic boutons. Our results represent the first quantitative measurement-using a highly reliable method-of the contribution of different cell types to the perisomatic innervation of pyramidal neurons, and may help to explain functional differences in their output properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Acidic
  • Animals
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure*
  • Interneurons / metabolism
  • Interneurons / ultrastructure*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / ultrastructure
  • Parvalbumins / analysis
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / ultrastructure*
  • Receptor, Cannabinoid, CB1 / analysis


  • Amino Acid Transport Systems, Acidic
  • Parvalbumins
  • Receptor, Cannabinoid, CB1
  • vesicular glutamate transporter 3, mouse