A cholinergic trigger drives learning-induced plasticity at hippocampal synapses.
Learning induces plastic changes in synapses. However, the regulatory molecules that orchestrate learning-induced synaptic changes are largely unknown. Although it is well established that cholinergic inputs from the medial septum modulate learning and memory, evidence for the cholinergic regulation of learning-induced synaptic plasticity is lacking. Here we find that the activation of muscarinic acetylcholine (ACh) receptors (mAChRs) mediates the contextual fear learning-driven strengthening of hippocampal excitatory pyramidal synapses through the synaptic incorporation of AMPA-type glutamate receptors (AMPARs). Contextual fear learning also enhances the strength of inhibitory synapses on hippocampal pyramidal CA1 neurons, in a manner mediated by the activation of, not mAChRs, but, nicotinic AChRs (nAChRs). We observe a significant correlation between the learning-induced increases in excitatory and inhibitory synaptic strength at individual pyramidal neurons. Understanding the mechanisms underlying cholinergic regulation of learning-induced hippocampal synaptic plasticity may help the development of new therapies for cognitive disorders.
1] Department of Physiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Japan [2] Department of Physiology and Neuroscience, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka 238-8580, Japan [3] Department of Systems Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube 755-8505, Japan.
Dai
D
Mitsushima
Akane
A
Sano
Takuya
T
Takahashi
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D055724:Electrophysiological Phenomena; D006624:Hippocampus / Q000166:cytology*; D007858:Learning / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D000109:Acetylcholine