Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants.

Disruption of neuronal signaling by soluble beta-amyloid has been implicated in deficits in short-term recall in the early stages of Alzheimer's disease. One potential target for beta-amyloid is the synapse, with evidence for differential interaction with both pre- and post-synaptic elements. Our previous work revealed an agonist-like action of soluble beta-amyloid (pM to nM) on isolated pre-synaptic terminals to increase [Ca(2+)]i, with apparent involvement of pre-synaptic nicotinic receptors.

Chronic nicotine alters nicotinic receptor-induced presynaptic Ca2+ responses in isolated nerve terminals.

Brain nicotinic receptors display pronounced permeability for Ca2+ and localize to presynaptic nerve terminals, in addition to postsynaptic sites. Chronic exposure to nicotine has been shown to alter brain nicotinic receptor expression, but the functional consequences for presynaptic Ca2+ have not been directly examined. Here, we used confocal imaging to assess Ca2+ responses in individual nerve terminals from cortices of mice treated up to 14 days with nicotine as compared to vehicle-treated controls.