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Changes in GABAergic markers accompany degradation of neuronal function in the primary visual cortex of senescent rats.

ABSTRACT: Numerous studies have reported age-dependent degradation of neuronal function in the visual cortex and have attributed this functional decline to weakened intracortical inhibition, especially GABAergic inhibition. However, whether this type of functional decline is linked to compromised GABAergic inhibition has not been fully confirmed. Here, we compared the neuronal response properties and markers of GABAergic inhibition in the primary visual cortex (V1) of young adult and senescent rats. Compared with those of young adult rats, old rats' V1 neurons exhibited significantly increased visually evoked responses and spontaneous activity, a decreased signal-to-noise ratio and reduced response selectivity for the stimulus orientation and motion direction. Additionally, the ratio of GABA-positive neurons to total cortical neurons in old rats was significantly decreased compared with that in young rats. Expression of the key GABA-synthesizing enzyme GAD67 was significantly lower in old rats than in young rats, although GAD65 expression showed a marginal difference between the two age groups. Further, expression of an important GABA_A receptor subunit, GABA_AR ?₁, was significantly attenuated in old rats relative to young ones. These results demonstrate that ageing may result in decreased GABAergic inhibition in the visual cortex and that this decrease in GABAergic inhibition accompanies neuronal function degradation.

SUBMITTER: Ding Y

PROVIDER: S-EPMC5668371 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Changes in GABAergic markers accompany degradation of neuronal function in the primary visual cortex of senescent rats.

Ding Yanxia Y Zheng Yuan Y Liu Tao T Chen Ting T Wang Changhua C Sun Qiushuang Q Hua Mutian M Hua Tianmiao T

Scientific reports 20171102 1

Numerous studies have reported age-dependent degradation of neuronal function in the visual cortex and have attributed this functional decline to weakened intracortical inhibition, especially GABAergic inhibition. However, whether this type of functional decline is linked to compromised GABAergic inhibition has not been fully confirmed. Here, we compared the neuronal response properties and markers of GABAergic inhibition in the primary visual cortex (V1) of young adult and senescent rats. Compa ...[more]

PMID: 29097694

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Project description:The maturation of the GABAergic system is a crucial determinant of cortical development during early postnatal life, when sensory circuits undergo a process of activity-dependent refinement. An altered excitatory/inhibitory balance has been proposed as a possible pathogenic mechanism of autism spectrum disorders (ASD). The homeobox-containing transcription factor Engrailed-2 (En2) has been associated to ASD, and En2 knockout (En2 (-/-)) mice show ASD-like features accompanied by a partial loss of cortical GABAergic interneurons. Here we studied GABAergic markers and cortical function in En2 (-/-) mice, by exploiting the well-known anatomical and functional features of the mouse visual system. En2 is expressed in the visual cortex at postnatal day 30 and during adulthood. When compared to age-matched En2 (+/+) controls, En2 (-/-) mice showed an increased number of parvalbumin (PV(+)), somatostatin (SOM(+)), and neuropeptide Y (NPY(+)) positive interneurons in the visual cortex at P30, and a decreased number of SOM(+) and NPY(+) interneurons in the adult. At both ages, the differences in distinct interneuron populations observed between En2 (+/+) and En2 (-/-) mice were layer-specific. Adult En2 (-/-) mice displayed a normal eye-specific segregation in the retino-geniculate pathway, and in vivo electrophysiological recordings showed a normal development of basic functional properties (acuity, response latency, receptive field size) of the En2 (-/-) primary visual cortex. However, a significant increase of binocularity was found in P30 and adult En2 (-/-) mice, as compared to age-matched controls. Differently from what observed in En2 (+/+) mice, the En2 (-/-) primary visual cortex did not respond to a brief monocular deprivation performed between P26 and P29, during the so-called "critical period." These data suggest that altered GABAergic circuits impact baseline binocularity and plasticity in En2 (-/-) mice, while leaving other visual functional properties unaffected.

Dataset Information

Changes in GABAergic markers accompany degradation of neuronal function in the primary visual cortex of senescent rats.

Publications

Changes in GABAergic markers accompany degradation of neuronal function in the primary visual cortex of senescent rats.

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