Dataset Information

GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients.

ABSTRACT: Glaucoma is an age-related neurodegenerative disease of the visual system, affecting both the eye and the brain. Yet its underlying metabolic mechanisms and neurobehavioral relevance remain largely unclear. Here, using proton magnetic resonance spectroscopy and functional magnetic resonance imaging, we investigated the GABAergic and glutamatergic systems in the visual cortex of glaucoma patients, as well as neural specificity, which is shaped by GABA and glutamate signals and underlies efficient sensory and cognitive functions. Our study shows that among the older adults, both GABA and glutamate levels decrease with increasing glaucoma severity regardless of age. Further, our study shows that the reduction of GABA but not glutamate predicts the neural specificity. This association is independent of the impairments on the retina structure, age, and the gray matter volume of the visual cortex. Our results suggest that glaucoma-specific decline of GABA undermines neural specificity in the visual cortex and that targeting GABA could improve the neural specificity in glaucoma.

SUBMITTER: Bang JW

PROVIDER: S-EPMC10310759 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients.

Bang Ji Won JW Parra Carlos C Yu Kevin K Wollstein Gadi G Schuman Joel S JS Chan Kevin C KC

Communications biology 20230629 1

Glaucoma is an age-related neurodegenerative disease of the visual system, affecting both the eye and the brain. Yet its underlying metabolic mechanisms and neurobehavioral relevance remain largely unclear. Here, using proton magnetic resonance spectroscopy and functional magnetic resonance imaging, we investigated the GABAergic and glutamatergic systems in the visual cortex of glaucoma patients, as well as neural specificity, which is shaped by GABA and glutamate signals and underlies efficient ...[more]

PMID: 37386293

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Project description:In advanced retinitis pigmentosa with retinal lesions, the lesion projection zone (LPZ) in the early visual cortex can be driven during visual tasks, while it remains unresponsive during passive viewing. We tested whether this finding translates to advanced glaucoma, a major cause of acquired blindness. During visual stimulation, 3T fMRI scans were acquired for participants with advanced glaucoma (n = 4; age range: 51-72) and compared to two reference groups, i.e., advanced retinitis pigmentosa (n = 3; age range: 46-78) and age-matched healthy controls with simulated defects (n = 7). The participants viewed grating patterns drifting in 8 directions (12 s) alternating with uniform gray (12 s), either during passive viewing (PV), i.e., central fixation, or during a one-back task (OBT), i.e., reports of succeeding identical motion directions. As another reference, a fixation-dot task condition was included. Only in glaucoma and retinitis pigmentosa but not in controls, fMRI-responses in the lesion projection zone (LPZ) of V1 shifted from negative for PV to positive for OBT (p = 0.024 and p = 0.012, respectively). In glaucoma, these effects also reached significance in V3 (p = 0.006), while in V2 there was a non-significant trend (p = 0.069). The general absence of positive responses in the LPZ during PV underscores the lack of early visual cortex bottom-up plasticity for acquired visual field defects in humans. Trends in our exploratory analysis suggesting the task-dependent LPZ responses to be inversely related to visual field loss, indicate the benefit of patient stratification strategies in future studies with greater sample sizes. We conclude that top-down mechanisms associated with task-elicited demands rather than visual cortex remapping appear to shape LPZ responses not only in retinitis pigmentosa, but also in glaucoma. These insights are of critical importance for the development of schemes for treatment and rehabilitation in glaucoma and beyond.

Project description:BackgroundPrevious reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABA(A) receptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABA(A) responses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABA(A) receptor mediated inhibitory postsynaptic currents (IPSCs). These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABA(A) IPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex.ResultsGABA(A) slow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABA(A) slow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABA(A) subunit-specific antagonist, furosemide, depressed spontaneous and evoked GABA(A) fast IPSCs, but not slow GABA(A)-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABA(A) fast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components.ConclusionGABA(A) slow IPSCs displayed durations that were approximately 4 fold longer than typical GABA(A)fast IPSCs, but shorter than GABA(B)-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABA(A) slow IPSCs into computational models of cortical function will help improve our understanding of cortical information processing.

Dataset Information

GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients.

Publications

GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients.

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