RT Journal Article
SR Electronic
T1 Enhanced Synaptic Inhibition in the Dorsolateral Geniculate Nucleus in a Mouse Model of Glaucoma
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0263-24.2024
DO 10.1523/ENEURO.0263-24.2024
VO 11
IS 7
A1 Van Hook, Matthew J.
A1 McCool, Shaylah
YR 2024
UL http://www.eneuro.org/content/11/7/ENEURO.0263-24.2024.abstract
AB Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output. While prior work has indicated unaltered glutamate receptor properties in the glaucomatous dLGN, it is unknown whether glaucoma impacts dLGN inhibition. Here, using DBA/2J mice, which develop elevated IOP beginning at 6–7 months of age, we tested whether the strength of inhibitory synapses on dLGN thalamocortical relay neurons is altered in response to the disease state. We found an enhancement of feedforward disynaptic inhibition arising from local interneurons along with increased amplitude of quantal inhibitory synaptic currents. A combination of immunofluorescence staining for the γ-aminobutyric acid (GABA)A-α1 receptor subunit, peak-scaled nonstationary fluctuation analysis, and measures of homeostatic synaptic scaling pointed to an ∼1.4-fold increase in GABA receptors at postsynaptic inhibitory synapses, although several pieces of evidence indicate a nonuniform scaling across inhibitory synapses within individual relay neurons. Together, these results indicate an increase in inhibitory synaptic strength in the glaucomatous dLGN, potentially pointing toward homeostatic compensation for disruptions in network and neuronal function triggered by increased IOP.