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Author Notes:

Andrew Sharott and Peter J. Magill, MRC Brain Network Dynamics Unit, University of Oxford, Oxford, OX1 3TH, United Kingdom. Emails: peter.magill@pharm.ox.ac.uk; andrewe.sharott@pharm.ox.ac.uk

We thank A. Rajkovic and C. Cozzari for generous gifts of antibodies, T. Harkany and R. Faram for early insights on secretagogin, and G. Hazell, B. Micklem, E. Norman, K. Whitworth, J. Janson, L. Conyers, C. Johnson and S. Jenkins for technical support.

The authors declare no competing financial interests.


Research Funding:

This work was supported by the Medical Research Council UK (MRC; awards MC_UU_12020/5 and MC_UU_12024/2 to P.J.M., and award MC_UU_12024/1 to A.S.), and a Marie Curie European Re‐integration Grant (SNAP‐PD) awarded by the European Union.

F.N.G. and E.K. were supported by University of Oxford Clarendon Fund Scholarships and the MRC.

R.S. was funded by a Wellcome Trust Clinical Fellowship (WT_RS_109030/Z/15/Z).

F.V. was supported by an MRC studentship.

Y.S. was supported by NIH support to Yerkes National Primate Centre (P51OD011132).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Zoology
  • Neurosciences & Neurology
  • calretinin
  • interneuron
  • neuronal diversity
  • RRID: AB_10000342
  • RRID: AB_94259
  • RRID: AB_2228331
  • RRID: AB_2269934
  • RRID: AB_10864618
  • RRID: AB_2194626
  • RRID: AB_2064130
  • secretagogin
  • striatum

Structural and molecular heterogeneity of calretinin‐expressing interneurons in the rodent and primate striatum


Journal Title:

Journal of Comparative Neurology


Volume 526, Number 5


, Pages 877-898

Type of Work:

Article | Final Publisher PDF


Calretinin-expressing (CR+) interneurons are the most common type of striatal interneuron in primates. However, because CR+ interneurons are relatively scarce in rodent striatum, little is known about their molecular and other properties, and they are typically excluded from models of striatal circuitry. Moreover, CR+ interneurons are often treated in models as a single homogenous population, despite previous descriptions of their heterogeneous structures and spatial distributions in rodents and primates. Here, we demonstrate that, in rodents, the combinatorial expression of secretagogin (Scgn), specificity protein 8 (SP8) and/or LIM homeobox protein 7 (Lhx7) separates striatal CR+ interneurons into three structurally and topographically distinct cell populations. The CR+/Scgn+/SP8+/Lhx7− interneurons are small-sized (typically 7–11 µm in somatic diameter), possess tortuous, partially spiny dendrites, and are rostrally biased in their positioning within striatum. The CR+/Scgn−/SP8−/Lhx7− interneurons are medium-sized (typically 12–15 µm), have bipolar dendrites, and are homogenously distributed throughout striatum. The CR+/Scgn−/SP8−/Lhx7+ interneurons are relatively large-sized (typically 12–20 µm), and have thick, infrequently branching dendrites. Furthermore, we provide the first in vivo electrophysiological recordings of identified CR+ interneurons, all of which were the CR+/Scgn−/SP8−/Lhx7− cell type. In the primate striatum, Scgn co-expression also identified a topographically distinct CR+ interneuron population with a rostral bias similar to that seen in both rats and mice. Taken together, these results suggest that striatal CR+ interneurons comprise at least three molecularly, structurally, and topographically distinct cell populations in rodents. These properties are partially conserved in primates, in which the relative abundance of CR+ interneurons suggests that they play a critical role in striatal microcircuits.

Copyright information:

© 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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