The role of calcium-permeable AMPA receptors in disynaptic feedforward inhibition in the rat prefrontal cortex

Abstract

Calcium permeable AMPA receptors (CP AMPARs) play an important role in synaptic trans mission and plasticity, but they also can induce neuronal death under certain pathological conditions. The involvement of CP AMPARs in the pathogenesis of many diseases of the central nervous system makes them an attractive target for selective pharmacological blockade, to prevent and relieve pathological processes. However, the practical application of selective CP AMPAR channel blockers requires a thorough study of their effects on the functioning of neural networks under the normal conditions. The goal of this study was to clarify the role of CP AMPARs in the regulation of firing thresholds in different types of cortical neurons, as well as their involvement in maintaining the excitation/inhibition balance in the cortex. To do this, we have investigated the effects of CP AMPARs blockade on the amplitude of excitatory postsynaptic potentials (EPSPs) and the threshold of action potentials evoked by extracellular stimulation. Whole cell current clamp recordings were carried out from pyramidal cells and fast spiking interneurons in the slices of rat medial prefrontal cortex. CP AMPARs were blocked with a selective channel blocker IEM 1460 (100 µM), the dicationic derivative of adamantane. It was found that the blockade of CP AMPARs reduced the ampli tude EPSPs in interneurons but not in pyramidal cells. In addition, it reduced the firing threshold in pyrami dal cells via partial suppression of feedforward inhibition. Thus, the blockade of CP AMPA receptors shifts the balance between cortical excitation and inhibition toward excitation.

Inter and Intralaminar Excitation of Parvalbumin Interneurons in Mouse Barrel Cortex

“…Thus, the larger EPSP amplitudes of L2/3 PV interneurons could be related to higher reciprocal connectivity. Calcium-permeable AMPA receptors have also been shown to impact fast-spiking interneuron synaptic responses (Bonsi et al, 2007;Zaitsev et al, 2012), and differences in their distribution between layers could contribute to the present findings.…”

“…Regardless of stimulation layer, response amplitude was greater for PV interneurons in L2/3 compared to L4. EPSP amplitude depends on a wide variety of factors including number of inputs, dendritic location, and ion channel and receptor makeup (Ali & Nelson, 2006;Bonsi et al, 2007;Otsuka & Kawaguchi, 2009;Zaitsev et al, 2012;Pala & Petersen, 2018;Das et al, 2021). The increased EPSP amplitude in L2/3 compared to L4 PV interneurons may therefore reflect some of these factors.…”

Inter and intralaminar excitation of parvalbumin interneurons in mouse barrel cortex

“…Thus, the larger EPSP amplitudes of L2/3 PV interneurons could be related to higher reciprocal connectivity. Calcium-permeable AMPA receptors have also been shown to impact fast-spiking interneuron synaptic responses [ 71 , 72 ], and differences in their distribution between layers could contribute to the present findings.…”