through M1 mAChRs would dominate in neurons with fully-replenished stores. Furthermore, studies showing that mAChR activation reduces cortico-cortical transmission have relied on electrical stimulation to evoke glutamate release, leaving the identity of the activated presynaptic terminals ambiguous. It is possible that distinct populations of intra-cortical synapses, such as those comprising local recurrent networks versus long-range intra-areal projections, might be differentially modulated by ACh. Indeed, in the CA1 region of the hippocampus, long-range perforant inputs from the entorhinal cortex are less inhibited by ACh than the Schaeffer collaterals arising from CA3 (Hasselmo and Schnell, 1994). The advent of optogenetic tools for selectively targeted difference populations of excitatory inputs (Gradinaru et al., 2007) will be a key development for elucidating the precise role of ACh on various circuit elements.
