The ability of acetylcholine to shift cortical flow of activity between the thalamo-cortical (TC) and cortico-cortical (CC) pathways has been the basis for models implicating the role of acetylcholine in attention. However, no conclusive mechanism has been provided for this shift and anatomical data linked to this theory is scarce. Nicotinic receptors have been associated with pre-synaptic enhancement of neurotransmitter release within the brain, yet our recent physiological data suggest that nicotine also acts by a pre-synaptic mechanism to lower synaptic efficacy (Levy et al., SfN 2004). The polar nicotine effects likely depend upon the relative densities and locations of the nicotinic receptor subtypes. Thus, we are performing dual labeling of the β2 subunit of nicotinic receptors and the layer V pyramidal neurons to localize the sites of nicotinic modulation on these cells across the cortical lamina. Using EM, we are looking for the presence of β2 on pre- and post-synaptic membranes of thalamo-cortical...