TY - JOUR
T1 - Intracellular Chloride Regulation in AVP+ and VIP+ Neurons of the Suprachiasmatic Nucleus
AU - Klett, Nathan J.
AU - Allen, Charles N.
N1 - Funding Information:
We thank Dr. Piotr Bregestovski for kindly providing us with the Cre-inducible Rosa26::Cl-Sensor mice and Mike Lasarev for help with statistical analysis. Olga Cravetchi managed the mouse breeding and genotyping. The work was supported by National Institutes of Health (NIH) grant NS036607 and a Medical Research Foundation of Oregon grant to CNA.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Several reports have described excitatory GABA transmission in the suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. However, there is disagreement regarding the prevalence, timing, and neuronal location of excitatory GABA transmission in the SCN. Whether GABA is inhibitory or excitatory depends, in part, on the intracellular concentration of chloride ([Cl-]i). Here, using ratiometric Cl- imaging, we have investigated intracellular chloride regulation in AVP and VIP-expressing SCN neurons and found evidence suggesting that [Cl-]i is higher during the day than during the night in both AVP+ and VIP+ neurons. We then investigated the contribution of the cation chloride cotransporters to setting [Cl-]i in these SCN neurons and found that the chloride uptake transporter NKCC1 contributes to [Cl-]i regulation in SCN neurons, but that the KCCs are the primary regulators of [Cl-]i in SCN neurons. Interestingly, we observed that [Cl-]i is differentially regulated between AVP+ and VIP+ neurons-a low concentration of the loop diuretic bumetanide had differential effects on AVP+ and VIP+ neurons, while blocking the KCCs with VU0240551 had a larger effect on VIP+ neurons compared to AVP+ neurons.
AB - Several reports have described excitatory GABA transmission in the suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. However, there is disagreement regarding the prevalence, timing, and neuronal location of excitatory GABA transmission in the SCN. Whether GABA is inhibitory or excitatory depends, in part, on the intracellular concentration of chloride ([Cl-]i). Here, using ratiometric Cl- imaging, we have investigated intracellular chloride regulation in AVP and VIP-expressing SCN neurons and found evidence suggesting that [Cl-]i is higher during the day than during the night in both AVP+ and VIP+ neurons. We then investigated the contribution of the cation chloride cotransporters to setting [Cl-]i in these SCN neurons and found that the chloride uptake transporter NKCC1 contributes to [Cl-]i regulation in SCN neurons, but that the KCCs are the primary regulators of [Cl-]i in SCN neurons. Interestingly, we observed that [Cl-]i is differentially regulated between AVP+ and VIP+ neurons-a low concentration of the loop diuretic bumetanide had differential effects on AVP+ and VIP+ neurons, while blocking the KCCs with VU0240551 had a larger effect on VIP+ neurons compared to AVP+ neurons.
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U2 - 10.1038/s41598-017-09778-x
DO - 10.1038/s41598-017-09778-x
M3 - Article
C2 - 28860458
AN - SCOPUS:85028638092
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 10226
ER -