Subsynaptic localization of nicotinic acetylcholine receptor subunits: A comparative study in the mouse and rat striatum

The striatum is the primary input station of the basal ganglia network, playing an essential role in sensorimotor, cognitive and motivational functions. Nicotinic acetylcholine receptors (nAChRs) were identified in nerve terminals of the striatum, where they are known to modulate neurotransmitter release, therefore critically regulating striatal functions. However, the subsynaptic (i.e. pre-, post- and extra-synaptic) localization of the different nAChRs subtypes present in the striatal synapses is still unclear, which might be associated with different roles in the control of synaptic transmission. In the present study we analyzed the subsynaptic distribution of particularly relevant nAChRs subunits, namely α7, α6, α4 and β2, in rat and mice striatal synapses (synaptosomes). In the rodent striatum we found that the α7 subunit, which predominantly forms homomeric nAChRs, was mainly present at the presynaptic active zone. The α4 and β2 subunits displayed a similar distribution, being primarily present at the presynaptic and/or extrasynaptic zones (mice and rats, respectively), which was expected since these two subunits together form heteropentameric nAChRs. In contrast, the α6 subunit was mainly present in the postsynaptic fraction, albeit being also present in pre- and extra-synaptic fractions. Altogether, this work details the striatal subsynaptic distribution of some of the main nAChRs subunits, underlining the possible relevance of striatal nAChRs in controlling neurotransmission, with potential relevance for Parkinson's disease, nicotine addiction and other dopaminergic disorders.