In contrast to the ability of nAChR stimulation to promote LTP in a number of brain areas, nAChR-mediated facilitation of GABA release reduces calcium levels in prefronto-cortical dendrites (Couey et al., 2007). In addition, activation of nAChRs can also decrease subsequent stimulation of calcium entry into cortical neurons in response to glutamate (Stevens et al., 2003). The decrease in glutamate-mediated calcium entry is mediated through activation of high affinity nAChRs, subsequent activation of the protein phosphatase calcineurin and inactivation of L-type calcium channels. If this mechanism is also recruited as a result of ACh signaling in vivo, it would suggest that one consequence of cholinergic activity in cortical neurons would be a significant decrease in subsequent calcium-mediated glutamate responses.
