title: Aβ impairs nicotinic regulation of inhibitory synaptic transmission and interneuron excitability in prefrontal cortex.
abstract: BACKGROUND
  Accumulation of β-amyloid (Aβ) and cholinergic deficiency are two prominent features of Alzheimer's disease (AD). To understand how Aβ-induced dysfunction of the nicotinic system may contribute to cognitive impairment in AD, we examined the effect of Aβ on nicotinic regulation of synaptic transmission and neuronal excitability in prefrontal cortex (PFC), a brain region critical for cognitive processes.
  
  
  RESULTS
  We found that activation of nicotinic acetylcholine receptors (nAChRs) with nicotine increased the inhibitory postsynaptic currents recorded in PFC pyramidal neurons, which was associated with the nicotine-induced increase in the excitability of PFC layer I GABAergic interneurons. Both effects of nicotine were disrupted by Aβ. However, Aβ did not impair nicotinic regulation of excitatory neurotransmission in PFC interneurons. The nicotinic effect on synaptic inhibition was also lost in transgenic mice with five familial Alzheimer's disease mutations. Inhibiting PKC attenuated nicotinic regulation of inhibitory, but not excitatory, neurotransmission.
  
  
  CONCLUSIONS
  Our study suggests that Aβ selectively impairs nicotinic regulation of inhibitory inputs to PFC pyramidal neurons, which might be due to its interference with PKC activation. Thus, in the PFC circuits of AD, the balance between inhibition and excitation under the control of nAChRs may be disturbed by Aβ.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. woodchen2015@163.com
authors: Guo-Jun
authors: GJ
authors: Chen
authors: Zhe
authors: Z
authors: Xiong
authors: Zhen
authors: Z
authors: Yan
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine