SPATIAL AND INTRACELLULAR RELATIONSHIPS BETWEEN THE α7 NICOTINIC ACETYLCHOLINE RECEPTOR AND THE VESICULAR ACETYLCHOLINE TRANSPORTER IN THE PREFRONTAL CORTEX OF RAT AND MOUSE

The alpha 7 subunit of the nicotinic acetylcholine receptor (alpha 7nAChR) is expressed in the prefrontal cortex (PFC), a brain region where these receptors are implicated in cognitive function and in the pathophysiology of schizophrenia. Activation of this receptor is dependent on release of acetylcholine (ACh) from axon terminals that contain the vesicular acetylcholine transporter (VAChT). Since rat and mouse models are widely used for studies of specific abnormalities in schizophrenia, we sought to determine the subcellular location of the alpha 7nAChR with respect to VAChT storage vesicles in axon terminals in the PFC in both species. For this, we used dual electron microscopic immunogold and immunoperoxidase labeling of antisera raised against the alpha 7nAChR and VAChT. In both species, the alpha 7nAChR-immunoreactivity ((-)ir) was principally identified within dendrites and dendritic spines, receptive to axon terminals forming asymmetric excitatory-type synapses, but lacking detectable alpha 7nAChR or VAChT-ir. Quantitative analysis of the rat PFC revealed that of alpha 7nAChR-labeled neuronal profiles, 65% (2991463) were postsynaptic structures (dendrites and dendritic spine) and only 22% (104/463) were axon terminals or small unmyelinated axons. In contrast, VAChT was principally localized to varicose vesicle-filled axonal profiles, without recognized synaptic specializations (n=240). Of the alpha 7nAChR-labeled axons, 47% (37/79) also contained VAChT, suggesting that ACh release is autoregulated through the presynaptic alpha 7nAChR. The VAChT-labeled terminals rarely formed synapses, but frequently apposed alpha 7nAChR-containing neuronal profiles. These results suggest that in rodent PFC, the alpha 7nAChR plays a major role in modulation of the postsynaptic excitation in spiny dendrites in contact with VAChT containing axons. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.