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Distinct timing in the activity of cannabinoid-sensitive and cannabinoid-insensitive basket cells

Abstract

Cannabinoids are powerful modulators of inhibition, yet the precise spike timing of cannabinoid receptor (CB1R)-expressing inhibitory neurons in relation to other neurons in the circuit is poorly understood. Here we found that the spike timing of CB1R-expressing basket cells, a major target for cannabinoids in the rat hippocampus, was distinct from the other main group of basket cells, the CB1R-negative. Despite receiving the same afferent inputs, the synaptic and biophysical properties of the two cell types were tuned to detect different features of activity. CB1R-negative basket cells responded reliably and immediately to subtle and repetitive excitation. In contrast, CB1R-positive basket cells responded later and did not follow repetitive activity, but were better suited to integrate the consecutive excitation of independent afferents. This temporal separation in the activity of the two basket cell types generated distinct epochs of somatic inhibition that were differentially affected by endocannabinoids.

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Figure 1: Identification of CB1R-positive and -negative basket cells.
Figure 2: Characterization of morphological, intrinsic and synaptic properties of CB1R-positive and -negative basket cells.
Figure 3: Distinct excitation of CB1R-positive and -negative basket cells.
Figure 4: Distinct dynamics of excitation of CB1R-positive and -negative basket cells.
Figure 5: Transient recruitment of CB1R-positive basket cells.
Figure 6: Distinct integration time windows in CB1R-positive and -negative basket cells.
Figure 7: Differential contribution of CB1R-positive and -negative basket cells to feed-forward and feedback inhibition.

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Acknowledgements

We thank P. Somogyi for his help in the morphological identification of basket cells and their discrimination from axo-axonic cells; C. Kapfer for his help in establishing immunohistochemical procedures; K. Mackie (University of Washington, Seattle) for his gift of the CB1R antibody; and J. Isaacson and the members of the Scanziani lab for comments on the manuscript. This work was funded by the US National Institutes of Health (MH71401, MH70058 and NIDA 5T32DA007315).

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Correspondence to Massimo Scanziani.

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Supplementary information

Supplementary Fig. 1a

Reconstructions of CB1R-positive and-negative basket cells. (PDF 678 kb)

Supplementary Fig. 1b

Reconstructions of CB1R-positive and-negative basket cells. (PDF 492 kb)

Supplementary Fig. 2

Model for the activation of CB1R-positive and -negative basket cells. (PDF 21 kb)

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Glickfeld, L., Scanziani, M. Distinct timing in the activity of cannabinoid-sensitive and cannabinoid-insensitive basket cells. Nat Neurosci 9, 807–815 (2006). https://doi.org/10.1038/nn1688

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