Trajectory of the main GABAergic interneuron populations from early development to old age in the rat primary auditory cortex.

Lydia Ouellet,Etienne De Villers-Sidani

doi:10.3389/fnana.2014.00040

Lydia Ouellet, Etienne De Villers-Sidani

Open Access

https://doi.org/10.3389/fnana.2014.00040

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Abstract

In both humans and rodents, decline in cognitive function is a hallmark of the aging process; the basis for this decrease has yet to be fully characterized. However, using aged rodent models, deficits in auditory processing have been associated with significant decreases in inhibitory signaling attributed to a loss of GABAergic interneurons. Not only are these interneurons crucial for pattern detection and other large-scale population dynamics, but they have also been linked to mechanisms mediating plasticity and learning, making them a prime candidate for study and modeling of modifications to cortical communication pathways in neurodegenerative diseases. Using the rat primary auditory cortex (A1) as a model, we probed the known markers of GABAergic interneurons with immunohistological methods, using antibodies against gamma aminobutyric acid (GABA), parvalbumin (PV), somatostatin (SOM), calretinin (CR), vasoactive intestinal peptide (VIP), choline acetyltransferase (ChAT), neuropeptide Y (NPY), and cholecystokinin (CCK) to document the changes observed in interneuron populations across the rat's lifespan. This analysis provided strong evidence that several but not all GABAergic neurons were affected by the aging process, showing most dramatic changes in expression of parvalbumin (PV) and somatostatin (SOM) expression. With this evidence, we show how understanding these trajectories of cell counts may be factored into a simple model to quantify changes in inhibitory signaling across the course of life, which may be applied as a framework for creating more advanced simulations of interneuronal implication in normal cerebral processing, normal aging, or pathological processes.

Highlights

The cerebral cortex is a complex computational machine, simultaneously processing environmental information through a delicate balance of excitation and inhibition
Our first results using markers for PV, SOM, CR, vasoactive intestinal peptide (VIP), choline acetyltransferase (ChAT), neuropeptide Y (NPY), and CCK revealed that GABAergic interneuron populations in A1 of rats from 9 to 750 days of age showed considerable fluctuation with time
Since gamma-aminobutyric acid (GABA) counts remain relatively stable after postnatal day 20 (P20), its relatively small decline later in life cannot account for the global fluctuations in interneuron markers we observed

Summary

Introduction

The cerebral cortex is a complex computational machine, simultaneously processing environmental information through a delicate balance of excitation and inhibition. Inhibitory interneurons constitute a clear minority compared to the number of excitatory neurons, they are highly influential, with important roles in cortical maturation, function, plasticity and organization of complex cortical networks underlying a wide range of functions (Lehmann et al, 2012) The majority of these cells in the cortex are inhibitory, and express gamma-aminobutyric acid (GABA) as their principal neurotransmitter (Dreifuss et al, 1969; Somogyi et al, 1983). These two subtypes represent only a fraction of known interneuron subtypes, and of important

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