Age‐dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors

Abstract

Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24-26 months old) and young (2-4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline.

Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons

“…Our previous study showed that there is glutamatergic tonic inhibition on GABAergic neurotransmission through the non-NMDA receptor, GluR5-containing kainate receptor. [14] In the present study, DNQX, a non-NMDA glutamatergic antagonist, significantly induced the increase of sIPSCs in the control and etomidate exposure groups, which suggests that there is glutamatergic tonic inhibition on GABAergic neurotransmission; etomidate exposure did not affect the glutamatergic tonic inhibition on GABAergic neurotransmission. However, DNQX did not induce the increase of sIPSCs in the propofol group, which suggests that there is no glutamatergic tonic inhibition on GABAergic neurotransmission, or impaired this pathway.…”

“…[14] Briefly, the rat was decapitated and its brain was removed after sedation with isoflurane; transverse hippocampal slices (250–300 micrometer, thick) were cut in ice-cold sucrose-artificial cerebrospinal fluid (aCSF) with a VT1000S microtome (Leica, Deerfield, IL, USA). One to four slices were recorded from one rat and one cell was recorded in one slice.…”

“…Cumulative probability plots obtained under different experimental conditions were compared using the nonparametric Kolmogorov-Smirnov (K-S test), which estimates the probability that two cumulative distributions differ from each other by chance alone. [14]…”

“…[13] Our previous study showed that non-N-methyl-D-aspartate (non-NMDA) receptors (glutamate receptor 5 [GluR5]-containing kainate receptor) regulate the inhibitory synaptic transmission through endogenous glutamate, which is involved in age-dependent cognitive decline. [14] However, the research on long-term effects of neonatal propofol and/or etomidate on inhibitory and excitatory neurotransmissions interplay is very sparse, especially concerning the effects of propofol and/or etomidate on the interplay between GABAergic and glutamatergic neurotransmissions. In this study, we explored the effects of neonatal propofol and etomidate exposure on GABA-mediated synaptic inhibition and glutamate receptors’ inputs on GABAergic synapses in hippocampal pyramidal neurons in the postnatal day 80–90 rats using electrophysiological recordings of acute hippocampal slices.…”

Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices

“…The data generated from these measurements were used to plot cumulative probability amplitude and inter-event interval graphs, with each distribution normalized to a maximal value of 1. Cumulative probability plots obtained under different experimental conditions were compared using the nonparametric Kolmogorov –Smirnov test (KS-T), which estimates the probability that two cumulative distributions differ from each other by chance alone (Xu et al, 2009). All numerical values are expressed as mean ± standard error of the mean (SEM) and statistical analyses were performed by using a paired Student’s t -tests as needed.…”