Circadian behavioral responses to light and optic chiasm-evoked glutamatergic EPSCs in the suprachiasmatic nucleus of ipRGC conditional vGlut2 knock-out mice

Michael G. Moldavan, Patricia J. Sollars, Michael R. Lasarev, Charles Allen, Gary E. Pickard

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0411-17.2018
JournaleNeuro
Volume5
Issue number3
DOIs
StatePublished - May 1 2018

Fingerprint

Vesicular Glutamate Transport Protein 2
Optic Chiasm
Suprachiasmatic Nucleus
Knockout Mice
Retinal Ganglion Cells
Pituitary Adenylate Cyclase-Activating Polypeptide
Light
Synaptic Transmission
Glutamic Acid
Biological Clocks
Circadian Clocks
Synaptic Vesicles
Lighting
Neurons

Keywords

  • Circadian rhythm
  • IpRGCs
  • Melanopsin
  • Retinohypothalamic tract
  • Suprachiasmatic nucleus
  • Vesicular glutamate transporter 2

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Circadian behavioral responses to light and optic chiasm-evoked glutamatergic EPSCs in the suprachiasmatic nucleus of ipRGC conditional vGlut2 knock-out mice. / Moldavan, Michael G.; Sollars, Patricia J.; Lasarev, Michael R.; Allen, Charles; Pickard, Gary E.

In: eNeuro, Vol. 5, No. 3, e0411-17.2018, 01.05.2018.

Research output: Contribution to journalArticle

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AB - 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.

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