PMID- 32406304
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20210602
IS  - 1552-4531 (Electronic)
IS  - 0748-7304 (Print)
IS  - 0748-7304 (Linking)
VI  - 35
IP  - 3
DP  - 2020 Jun
TI  - The Excitatory Effects of GABA within the Suprachiasmatic Nucleus: Regulation of 
      Na-K-2Cl Cotransporters (NKCCs) by Environmental Lighting Conditions.
PG  - 275-286
LID - 10.1177/0748730420924271 [doi]
AB  - The suprachiasmatic nucleus (SCN) contains a pacemaker that generates circadian 
      rhythms and entrains them with the 24-h light-dark cycle (LD). The SCN is 
      composed of 16,000 to 20,000 heterogeneous neurons in bilaterally paired nuclei. 
      gamma-amino butyric acid (GABA) is the primary neurochemical signal within the SCN 
      and plays a key role in regulating circadian function. While GABA is the primary 
      inhibitory neurotransmitter in the brain, there is now evidence that GABA can 
      also exert excitatory effects in the adult brain. Cation chloride cotransporters 
      determine the effects of GABA on chloride equilibrium, thereby determining 
      whether GABA produces hyperpolarizing or depolarizing actions following 
      activation of GABA(A) receptors. The activity of Na-K-2Cl cotransporter1 (NKCC1), 
      the most prevalent chloride influx cotransporter isoform in the brain, plays a 
      critical role in determining whether GABA has depolarizing effects. In the 
      present study, we tested the hypothesis that NKCC1 protein expression in the SCN 
      is regulated by environmental lighting and displays daily and circadian changes 
      in the intact circadian system of the Syrian hamster. In hamsters housed in 
      constant light (LL), the overall NKCC1 immunoreactivity (NKCC1-ir) in the SCN was 
      significantly greater than in hamsters housed in LD or constant darkness (DD), 
      although NKCC1 protein levels in the SCN were not different between hamsters 
      housed in LD and DD. In hamsters housed in LD cycles, no differences in NKCC1-ir 
      within the SCN were observed over the 24-h cycle. NKCC1 protein in the SCN was 
      found to vary significantly over the circadian cycle in hamsters housed in 
      free-running conditions. Overall, NKCC1 protein was greater in the ventral SCN 
      than in the dorsal SCN, although no significant differences were observed across 
      lighting conditions or time of day in either subregion. These data support the 
      hypothesis that NKCC1 protein expression can be regulated by environmental 
      lighting and circadian mechanisms within the SCN.
FAU - McNeill, John K 4th
AU  - McNeill JK 4th
AD  - Neuroscience Institute and Center for Behavioral Neuroscience, Georgia State 
      University, Atlanta, Georgia.
FAU - Walton, James C
AU  - Walton JC
AUID- ORCID: 0000-0002-3049-1029
AD  - Neuroscience Institute and Center for Behavioral Neuroscience, Georgia State 
      University, Atlanta, Georgia.
FAU - Ryu, Vitaly
AU  - Ryu V
AD  - Neuroscience Institute and Center for Behavioral Neuroscience, Georgia State 
      University, Atlanta, Georgia.
FAU - Albers, H Elliott
AU  - Albers HE
AUID- ORCID: 0000-0001-7491-3978
AD  - Neuroscience Institute and Center for Behavioral Neuroscience, Georgia State 
      University, Atlanta, Georgia.
LA  - eng
GR  - F32 NS092545/NS/NINDS NIH HHS/United States
GR  - R01 NS078220/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200514
PL  - United States
TA  - J Biol Rhythms
JT  - Journal of biological rhythms
JID - 8700115
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - Circadian Rhythm/physiology/*radiation effects
MH  - Cricetinae
MH  - Environment
MH  - *Light
MH  - Male
MH  - Mesocricetus
MH  - Neurons/physiology/radiation effects
MH  - Photoperiod
MH  - Solute Carrier Family 12, Member 2/*genetics
MH  - Suprachiasmatic Nucleus/*physiology/radiation effects
MH  - gamma-Aminobutyric Acid/*physiology
PMC - PMC8060922
MID - NIHMS1687955
OTO - NOTNLM
OT  - GABAA receptors
OT  - chloride
OT  - circadian
OT  - entrainment
OT  - phase shifting
COIS- CONFLICT OF INTEREST STATEMENT The authors have no potential conflicts of 
      interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2020/05/15 06:00
MHDA- 2021/05/29 06:00
PMCR- 2021/06/01
CRDT- 2020/05/15 06:00
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2020/05/15 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - 10.1177/0748730420924271 [doi]
PST - ppublish
SO  - J Biol Rhythms. 2020 Jun;35(3):275-286. doi: 10.1177/0748730420924271. Epub 2020 
      May 14.