Cortical parvalbumin and somatostatin GABA neurons express distinct endogenous modulators of nicotinic acetylcholine receptors

Inhibition from GABAergic interneurons in brain circuits is a critical component of cognitive function. This inhibition is regulated through a diverse network of neuromodulation. A number of recent studies suggest that one of the major regulators of interneuron function is nicotinic acetylcholinergic transmission and dysregulation of both systems is common in psychiatric conditions. However, how nicotinic modulation impacts specific subpopulations of diverse GABAergic interneurons remains in question. One potential way of conferring specificity to the convergence of GABAergic and nicotinic signaling is through the expression of a unique family of nicotinic acetycholine receptor modulators, the Lynx family. The present study sought to identify members of the Lynx family enriched in cortical interneurons and to elucidate subpopulations of GABAergic neurons that express unique nicotinic modulators.

This work shows that distinct subpopulations of GABAergic interneurons express unique Lynx family members. The pattern of expression of Lynx family members within interneurons places them in a unique position to potentially regulate the convergence of GABAergic and nicotinic systems, dysfunction of which are characteristic of psychiatric disorders.

We utilize double fluorescence in situ hybridization to examine the interneuronal expression of the Lynx family in adult mouse visual cortex. We find that two of the Lynx family members, Lynx1 and Lypd6, are enriched in interneuron populations in cortex. Nearly all parvalbumin interneurons express Lynx1 but we did not detect Lypd6 in this population. Conversely, in somatostatin interneurons Lypd6 was found in a subset localized to deep cortical layers but no somatostatin neurons show detectable levels of Lynx1. Using a combination of genetic and viral manipulations we further show that a subpopulation of deep-layer cortico-cortical long-range somatostatin neurons also express Lypd6. Conclusions: This work shows that distinct subpopulations of GABAergic interneurons express unique Lynx family members. The pattern of expression of Lynx family members within interneurons places them in a unique position to potentially regulate the convergence of GABAergic and nicotinic systems, dysfunction of which are characteristic of psychiatric disorders.