Subunit composition of α5‐containing nicotinic receptors in the rodent habenula

Petra Scholze,Sigismund Huck,Gabriele Koth,Avi Orr‐Urtreger

doi:10.1111/j.1471-4159.2012.07714.x

Petra Scholze, Sigismund Huck + Show 2 more

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https://doi.org/10.1111/j.1471-4159.2012.07714.x

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Abstract

Gene association studies in humans have linked the α5 subunit gene CHRNA5 to an increased risk for nicotine dependence. In the CNS, nicotinic acetylcholine receptors (nAChRs) that contain the α5 subunit are expressed at relatively high levels in the habenulo-interpeduncular system. Recent experimental evidence furthermore suggests that α5-containing receptors in the habenula play a key role in controlling the intake of nicotine in rodents. We have now analysed the subunit composition of hetero-oligomeric nAChRs in the habenula of postnatal day 18 (P18) C57Bl/6J control mice and of mice with deletions of the α5, the β2, or the β4 subunit genes. Receptors consisting of α3β4*1 clearly outnumbered α4β2*-containing receptors not only in P18 but also in adult mice. We found low levels of α5-containing receptors in both mice (6%) and rats (2.5% of overall nAChRs). Observations in β2 and β4 null mice indicate that although α5 requires the presence of the β4 subunit for assembling (but not of β2), α5 in wild-type mice assembles into receptors that also contain the subunits α3, β2, and β4.

Highlights

These results are in keeping with the rat superior cervical ganglion (SCG), where about 25-30% of heteromeric nicotinic acetylcholine receptor (nAChR) are of the a3b4a5 type (Mao et al 2006)
Recent observations assign a5-containing nAChRs in the habenular complex a key role in controlling nicotine consumption (Fowler et al 2011; Frahm et al 2011) and nicotine withdrawal (Salas et al 2009). a5 may require the presence of the b4 subunit, because decreased signs of nicotine withdrawal have been observed in mice lacking a5 and in b4 knockout (KO) animals (Salas et al 2004, 2009; De Biasi and Salas 2008)
Soon after the identification of neuronal-type nAChRs it became clear that a fairly large variety of such receptors are expressed at a remarkable density in the habenula, a pair of small nuclei above the thalamus (Wada et al 1989; Hill et al 1993; Zoli et al 1998)

Summary

Introduction

Observations in b2 and b4 null mice indicate that a5 requires the presence of the b4 subunit for assembling (but not of b2), a5 in wild-type mice assembles into receptors that contain the subunits a3, b2, and b4. All a5-containing receptors are lost in the SCG of mice lacking the b4 subunit These results are in keeping with the rat SCG, where about 25-30% of heteromeric nAChRs are of the a3b4a5 type (Mao et al 2006). A5 may require the presence of the b4 subunit, because decreased signs of nicotine withdrawal have been observed in mice lacking a5 and in b4 knockout (KO) animals (Salas et al 2004, 2009; De Biasi and Salas 2008) Recent observations assign a5-containing nAChRs in the habenular complex a key role in controlling nicotine consumption (Fowler et al 2011; Frahm et al 2011) and nicotine withdrawal (Salas et al 2009). a5 may require the presence of the b4 subunit, because decreased signs of nicotine withdrawal have been observed in mice lacking a5 and in b4 knockout (KO) animals (Salas et al 2004, 2009; De Biasi and Salas 2008)

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