Layer-specific potentiation of network GABAergic inhibition in the CA1 area of the hippocampus

Abstract

One of the most important functions of GABAergic inhibition in cortical regions is the tight control of spatiotemporal activity of principal neuronal ensembles. However, electrophysiological recordings do not provide sufficient spatial information to determine the spatiotemporal properties of inhibitory plasticity. Using Voltage Sensitive Dye Imaging (VSDI) in mouse hippocampal slices, we demonstrate that GABAA-mediated field inhibitory postsynaptic potentials undergo layer-specific potentiation upon activation of metabotropic glutamate receptors (mGlu). VSDI recordings allowed detection of pharmacologically isolated GABAA-dependent hyperpolarization signals. Bath-application of the selective group-I mGlu receptor agonist, (S)-3,5-Dihydroxyphenylglycine (DHPG), induces an enhancement of the GABAergic VSDI-recorded signal, which is more or less pronounced in different hippocampal layers. This potentiation is mediated by mGlu5 and downstream activation of IP3 receptors. Our results depict network GABAergic activity in the hippocampal CA1 region and its sub-layers, showing also a novel form of inhibitory synaptic plasticity tightly coupled to glutamatergic activity.

Pre-plaque Aß-Mediated Impairment of Synaptic Depotentiation in a Transgenic Rat Model of Alzheimer’s Disease Amyloidosis

“…At a circuit level, different CA1 pyramidal cells have different inputs and outputs and perform multiple tasks in parallel (Slomianka et al, 2011; Soltesz and Losonczy, 2018). This diversity is reflected in the expression of different receptors and types of plasticity at different input synapses (Roth and Leung, 1995; Colavita et al, 2016; Brzdak et al, 2019). Moreover, the susceptibility of LTP at the different synaptic inputs to disruption by Aß varies.…”

“…Recently, it has become clear that CA1 pyramidal neurons with cell bodies either near the stratum radiatum or stratum oriens generally form different networks, with the latter having much more extensive basal dendritic trees with a strong input from CA2 (Graves et al, 2012; Soltesz and Losonczy, 2018). The known different signaling pathways mediating LTP at these synapses (Roth and Leung, 1995; Colavita et al, 2016; Brzdak et al, 2019) and the finding that spines have high turnover rates in stratum oriens (Pfeiffer et al, 2018), may help explain the relative resistance of synaptic plasticity at basal synapses to disruption of both LTP and depotentiation. A significant but relatively poorly explored question for AD research is to understand why only certain pathways are affected early in the disease process (Fu et al, 2018).…”

Mapping of excitatory and inhibitory postsynaptic potentials of neuronal populations in hippocampal slices using the GEVI, ArcLight

“…It is known that approximately 11% of the neuronal population in the hippocampal CA1 region are interneurons[50, 51] with each of them locally projecting GABAergic inputs to several hundreds of excitatory neurons[4, 52]. ArcLight was able to spatially discriminate the network of both depolarization and hyperpolarization in the hippocampal CA1 circuitry in a manner consistent with known circuitry[52, 53].…”

GEVI cell‐type specific labelling and a manifold learning approach provide evidence for lateral inhibition at the population level in the mouse hippocampal CA1 area

“…Optical recordings using voltage sensitive dyes address the issue of spatial information and provide a more direct way to study depolarization and hyperpolarization of membrane potential by reporting membrane voltage rather than field potentials. However, the use of voltage sensitive dyes falls short in cell-type specificity as organic dyes tend to stain all cellular membranes and intracellular dye loading experiments have similar restrictions with intracellular recordings as far as the number of cells assessed (Colavita et al, 2016;Tominaga et al, 2018;Wright & Jackson, 2015). Optogenetic control using effector proteins, most often channelrhodopsin, allow for light-scale precision and type-specific stimulation of targeted cells but do not report the electrical activity of the cells in question (Buetfering et al, 2014;English et al, 2017;Roux et al, 2014Roux et al, , 2017Stark et al, 2014).…”