Circadian Behavioral Responses to Light and Optic Chiasm-Evoked Glutamatergic EPSCs in the Suprachiasmatic Nucleus of ipRGC Conditional vGlut2 Knock-Out Mice

Authors

Michael G. Moldavan, Oregon Health and Science University
Patricia J. Sollars, University of Nebraska-LincolnFollow
Michael R. Lasarev, Oregon Health and Science University
Charles N. Allen, Oregon Health and Science University
Gary E. Pickard, University of Nebraska-LincolnFollow

ORCID IDs

0000-0003-4039-0325

0000-0002-1731-0502

0000-0002-1896-2705

0000-0002-3689-2878

Document Type

Article

Date of this Version

2018

Citation

May/June 2018, 5(3) e0411-17.2018 1–18

Comments

Copyright 2018 Moldavan et al.

Open access

DOI:http://dx.doi.org/10.1523/ENEURO.0411-17.2018

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, there is no direct evidence that all ipRGC glutamatergic neurotransmission is eliminated in vGlut2 cKOs. Here, we examined two lines of ipRGC vGlut2 cKO mice for SCN-mediated behavioral responses under several lighting conditions and for ipRGC glutamatergic neurotransmission in the SCN. Circadian behavioral responses varied from a very limited response to light to near normal photoentrainment. After collecting behavioral data, hypothalamic slices were prepared and evoked EPSCs (eEPSCs) were recorded from SCN neurons by stimulating the optic chiasm. In cKOs, glutamatergic eEPSCs were recorded and all eEPSC parameters examined (stimulus threshold, amplitude, rise time or time-to-peak and stimulus strength to evoke a maximal response) were similar to controls. We conclude that a variable number but functionally significant percentage of ipRGCs in two vGlut2 cKO mouse lines continue to release glutamate. Thus, the residual SCN-mediated light responses in these cKO mouse lines cannot be attributed solely to ipRGC PACAP release.