Not All That Is Gold Glitters: PV-IRES-Cre Mouse Line Shows Low Efficiency of Labeling of Parvalbumin Interneurons in the Perirhinal Cortex.

Maximiliano José Nigro,Hinako Kirikae,Rajeevkumar Raveendran Nair,Kasper Kjelsberg,Menno P Witter

doi:10.3389/fncir.2021.781928

Maximiliano José Nigro, Hinako Kirikae + Show 3 more

Open Access

https://doi.org/10.3389/fncir.2021.781928

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Abstract

The wide diversity of cortical inhibitory neuron types populating the cortex allows the assembly of diverse microcircuits and endows these circuits with different computational properties. Thus, characterizing neuronal diversity is fundamental to describe the building blocks of cortical microcircuits and probe their function. To this purpose, the mouse has emerged as a powerful tool to genetically label and manipulate specific inhibitory cell-types in the mammalian brain. Among these cell-types, the parvalbumin-expressing interneuron type (PV-INs) is perhaps the most characterized. Several mouse lines have been generated to target PV-INs. Among these mouse lines, the PV-IRES-Cre lines is the most widely used and demonstrated a high specificity and efficiency in targeting PV-INs in different cortical areas. However, a characterization of the performance across cortical regions is still missing. Here we show that the PV-IRES-Cre mouse line labels only a fraction of PV immunoreactive neurons in perirhinal cortex and other association areas. Our results point to a yet uncharacterized diversity within the PV-INs and emphasize the need to characterize these tools in specific cortical areas.

Highlights

The cerebral cortex is populated by a wide diversity of glutamatergic and GABAergic neurons (Harris and Shepherd, 2015)
This result suggests that the PV-IRES-Cre mouse line is very inefficient in labeling PV expressing GABAergic neurons in the mouse perirhinal cortex (PER)
We demonstrate here that the PV-IRES-Cre mouse line has a low efficiency in labeling Parvalbumin-expressing GABAergic neurons (PV-INs) in PER and this phenomenon might be a common feature of associative areas of the cerebral cortex

Summary

Introduction

The cerebral cortex is populated by a wide diversity of glutamatergic and GABAergic neurons (Harris and Shepherd, 2015). The study of neuronal diversity was propelled by the discovery of molecular markers that are expressed by neuronal classes. GABAergic neurons can be broadly divided in three major classes according to the non-overlapping expression of parvalbumin (PV), somatostatin (SST) and 5-hydroxytryptamine 3a receptor (5HT3aR) (Tremblay et al, 2016). The discovery of molecular markers has been exploited to produce transgenic mouse lines expressing fluorophores or recombinases to label or manipulate specific neuronal classes (Madisen et al, 2010; Taniguchi et al, 2011). Parvalbumin-expressing GABAergic neurons (PV-INs) are the major group of inhibitory neurons in the mammalian cortex, representing about 40% of the GABAergic population (Tremblay et al, 2016).

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