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Effects of GABACR and mGluR1 antagonists on contrast response functions of Sprague-Dawley and P23H rat retinal ganglion cells.

Abstract The GABACR antagonist TPMPA and the mGluR1 antagonist JNJ16259685 have been shown previously to alter the sensitivity of retinal ganglion cells (RGCs) in the Sprague-Dawley (SD) rat and P23H rat (animal model of retinitis pigmentosa) to brief flashes of light. In order to better understand the effects of these antagonists on the visual responses of SD and P23H rat RGCs, I examined the responses of RGCs to a drifting sinusoidal grating of various contrasts. Multielectrode array recordings were made from RGCs to a drifting sinusoidal grating of a spatial frequency of 1 cycle/mm and a temporal frequency of 2 cycles/s. In both SD and P23H rat retinas, contrast response functions were found to have a variable shape across cells. Some cells showed saturation of responses at high contrast levels while others did not. Whereas 49% of SD rat RGCs exhibited response saturation, only 14% of P23H rat RGCs showed response saturation. TPMPA decreased the responses of saturating SD rat RGCs to low (6% to 13%) grating contrasts but increased the response to the highest contrast (83%) tested. JNJ16259685 did not significantly affect the contrast response functions of either saturating or non-saturating SD rat RGCs. In contrast, both TPMPA and JNJ16259685 increased the responses of saturating and non-saturating P23H rat RGCs to all grating contrasts. Neither TPMPA nor JNJ16259685 affected the contrast thresholds of SD rat RGCs, but both antagonists lowered the contrast thresholds of P23H rat RGCs. Overall, the findings show that GABACR and mGluR1 antagonists have differential effects on the contrast response functions of SD and P23H rat RGCs. Notably, these receptor antagonists increase the responsiveness of P23H rat RGCs to both low and high contrast visual stimuli.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 29253887
OWN - NLM
STAT- MEDLINE
DCOM- 20180112
LR  - 20180112
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 12
DP  - 2017
TI  - Effects of GABACR and mGluR1 antagonists on contrast response functions of
      Sprague-Dawley and P23H rat retinal ganglion cells.
PG  - e0189980
LID - 10.1371/journal.pone.0189980 [doi]
AB  - The GABACR antagonist TPMPA and the mGluR1 antagonist JNJ16259685 have been shown
      previously to alter the sensitivity of retinal ganglion cells (RGCs) in the
      Sprague-Dawley (SD) rat and P23H rat (animal model of retinitis pigmentosa) to
      brief flashes of light. In order to better understand the effects of these
      antagonists on the visual responses of SD and P23H rat RGCs, I examined the
      responses of RGCs to a drifting sinusoidal grating of various contrasts.
      Multielectrode array recordings were made from RGCs to a drifting sinusoidal
      grating of a spatial frequency of 1 cycle/mm and a temporal frequency of 2
      cycles/s. In both SD and P23H rat retinas, contrast response functions were found
      to have a variable shape across cells. Some cells showed saturation of responses 
      at high contrast levels while others did not. Whereas 49% of SD rat RGCs
      exhibited response saturation, only 14% of P23H rat RGCs showed response
      saturation. TPMPA decreased the responses of saturating SD rat RGCs to low (6% to
      13%) grating contrasts but increased the response to the highest contrast (83%)
      tested. JNJ16259685 did not significantly affect the contrast response functions 
      of either saturating or non-saturating SD rat RGCs. In contrast, both TPMPA and
      JNJ16259685 increased the responses of saturating and non-saturating P23H rat
      RGCs to all grating contrasts. Neither TPMPA nor JNJ16259685 affected the
      contrast thresholds of SD rat RGCs, but both antagonists lowered the contrast
      thresholds of P23H rat RGCs. Overall, the findings show that GABACR and mGluR1
      antagonists have differential effects on the contrast response functions of SD
      and P23H rat RGCs. Notably, these receptor antagonists increase the
      responsiveness of P23H rat RGCs to both low and high contrast visual stimuli.
FAU - Jensen, Ralph
AU  - Jensen R
AUID- ORCID: http://orcid.org/0000-0001-6696-2382
AD  - Research Service, VA Boston Healthcare System, Boston, Massachusetts, United
      States of America.
LA  - eng
PT  - Journal Article
DEP - 20171218
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (GABA-C receptor)
RN  - 0 (Receptors, GABA)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (metabotropic glutamate receptor type 1)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Calibration
MH  - Disease Models, Animal
MH  - Electrodes
MH  - Electrophysiology
MH  - Female
MH  - Homozygote
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA/*metabolism
MH  - Receptors, Metabotropic Glutamate/*antagonists & inhibitors/metabolism
MH  - Retina/pathology
MH  - Retinal Ganglion Cells/*metabolism
MH  - Retinitis Pigmentosa/*metabolism
PMC - PMC5734767
EDAT- 2017/12/19 06:00
MHDA- 2018/01/13 06:00
CRDT- 2017/12/19 06:00
PHST- 2017/08/15 00:00 [received]
PHST- 2017/12/06 00:00 [accepted]
PHST- 2017/12/19 06:00 [entrez]
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
AID - 10.1371/journal.pone.0189980 [doi]
AID - PONE-D-17-30203 [pii]
PST - epublish
SO  - PLoS One. 2017 Dec 18;12(12):e0189980. doi: 10.1371/journal.pone.0189980.
      eCollection 2017.