Activation of alpha 7 nicotinic acetylcholine receptors facilitates long-term potentiation at the hippocampal-prefrontal cortex synapses in vivo

摘要

Activation of alpha 7 nAChRs has been shown to improve performance in a variety of nonclinical assays of cognitive function. The role of alpha 7 nAChRs in cognitive processes is likely related to their role in modulating synaptic transmission and plasticity that have been reported in cell culture, brain slices, and intact animals. Here we report the effects of the alpha 7 nAChR agonist FRM-17874 on synaptic plasticity within the hippocampal-medial prefrontal cortex pathway. Long-term potentiation (LTP) was generated by tetanic stimulation of CA1/subiculum region in urethane anesthetized male rats. Compared to saline controls, FRM-17874 significantly increased LTP (F-(3,F-16)=10.39, p=0.0005) at doses of 0.3 and 1.0 mg/kg but not with 3.0 mg/kg, injected subcutaneously. Considering the physiological role of hippocampal LTP in mnemonic functions and memory formation, and the role of the hippocampal - prefrontal cortex pathway in working memory, the described neurophysiological effects could be a contributing mechanism underlying the cognitive effects of a7 nAChRs activation. (C) 2016 Elsevier B.V. and ECNP. All rights reserved.