| First Author | Lozada AF | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 22 | Pages | 7651-61 |
| PubMed ID | 22649244 | Mgi Jnum | J:185201 |
| Mgi Id | MGI:5427759 | Doi | 10.1523/JNEUROSCI.6246-11.2012 |
| Citation | Lozada AF, et al. (2012) Glutamatergic Synapse Formation is Promoted by alpha7-Containing Nicotinic Acetylcholine Receptors. J Neurosci 32(22):7651-61 |
| abstractText | Glutamate is the primary excitatory transmitter in adult brain, acting through synapses on dendritic spines and shafts. Early in development, however, when glutamatergic synapses are only beginning to form, nicotinic cholinergic excitation is already widespread; it is mediated by acetylcholine activating nicotinic acetylcholine receptors (nAChRs) that generate waves of activity across brain regions. A major class of nAChRs contributing at this time is a species containing alpha7 subunits (alpha7-nAChRs). These receptors are highly permeable to calcium, influence a variety of calcium-dependent events, and are diversely distributed throughout the developing CNS. Here we show that alpha7-nAChRs unexpectedly promote formation of glutamatergic synapses during development. The dependence on alpha7-nAChRs becomes clear when comparing wild-type (WT) mice with mice constitutively lacking the alpha7-nAChR gene. Ultrastructural analysis, immunostaining, and patch-clamp recording all reveal synaptic deficits when alpha7-nAChR input is absent. Similarly, nicotinic activation of alpha7-nAChRs in WT organotypic culture, as well as cell culture, increases the number of glutamatergic synapses. RNA interference demonstrates that the alpha7-nAChRs must be expressed in the neuron being innervated for normal innervation to occur. Moreover, the deficits persist throughout the developmental period of major de novo synapse formation and are still fully apparent in the adult. GABAergic synapses, in contrast, are undiminished in number under such conditions. As a result, mice lacking alpha7-nAChRs have an altered balance in the excitatory/inhibitory input they receive. This ratio represents a fundamental feature of neural networks and shows for the first time that endogenous nicotinic cholinergic signaling plays a key role in network construction. |
