Functional consequences of neuropeptide and small-molecule co-transmission

Nat Rev Neurosci. 2017 Jul;18(7):389-403. doi: 10.1038/nrn.2017.56. Epub 2017 Jun 8.


Colocalization of small-molecule and neuropeptide transmitters is common throughout the nervous system of all animals. The resulting co-transmission, which provides conjoint ionotropic ('classical') and metabotropic ('modulatory') actions, includes neuropeptide- specific aspects that are qualitatively different from those that result from metabotropic actions of small-molecule transmitter release. Here, we focus on the flexibility afforded to microcircuits by such co-transmission, using examples from various nervous systems. Insights from such studies indicate that co-transmission mediated even by a single neuron can configure microcircuit activity via an array of contributing mechanisms, operating on multiple timescales, to enhance both behavioural flexibility and robustness.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Models, Neurological
  • Neurons / physiology*
  • Neuropeptides / physiology*
  • Neurotransmitter Agents / physiology*
  • Synaptic Transmission / physiology*


  • Neuropeptides
  • Neurotransmitter Agents