Regulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors

Abstract

Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the central nervous system and participate in a variety of physiological functions. Recent advances have revealed roles of nAChRs in the regulation of synaptic transmission and synaptic plasticity, particularly in the hippocampus and midbrain dopamine centers. In general, activation of nAChRs causes membrane depolarization and directly and indirectly increases the intracellular calcium concentration. Thus, when nAChRs are expressed on presynaptic membranes their activation generally increases the probability of neurotransmitter release. When expressed on postsynaptic membranes, nAChR-initiated calcium signals and depolarization activate intracellular signaling mechanisms and gene transcription. Together, the presynaptic and postsynaptic effects of nAChRs generate and facilitate the induction of long-term changes in synaptic transmission. The direction of hippocampal nAChR-mediated synaptic plasticity - either potentiation or depression - depends on the timing of nAChR activation relative to coincident presynaptic and postsynaptic electrical activity, and also depends on the location of cholinergic stimulation within the local network. Therapeutic activation of nAChRs may prove efficacious in the treatment of neuropathologies where synaptic transmission is compromised, as in Alzheimer's or Parkinson's disease.

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

“…The permeability ratio PCa/PNa, which is the relative permeability of calcium to sodium ions, was then estimated using the Goldmann-Hodgkin-Katz constant field equation [16,17] . The PCa/PNa ratio estimated in this way was ~2 for heteromeric neuronal non-α7 nAChRs, and >10 for homomeric α7 or the heteromeric α9/α10 nAChRs [2,3,7,8] . However, this relative approach has serious limitations.…”

“…The nAChRs are widely expressed in the brain, located both at the synapse (presynaptically and postsynaptically) as well as extrasynaptically [1,2] . Presynaptic and preterminal nAChRs can enhance neurotransmitter release, postsynaptic nAChRs can contribute to fast excitatory transmission, and extrasynaptic nAChRs can modulate many neurotransmitter systems by influencing neuronal excitability and/or intracellular processes [1][2][3] . The nAChRs play important modulatory roles in neuronal development and synaptic plasticity, participating in cognitive functions such as learning, memory, and attention.…”

“…Some are homomeric nAChRs, such as α7 receptors which contain five α7 subunits, and others are heteromeric nAChRs, which comprise α and β subunits [1] . Different subtypes of neuronal nAChRs are known to be differentially permeable to calcium ions (Ca 2+ ) [2,3,8] . The α7 nAChR subtype has one of the highest permeabilities to calcium [7] , the activation of which can raise cytoplasmic calcium levels and trigger a series of calcium-dependent intracellular processes.…”

α4* Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex

“…Neuronal nAChRs are ligand-gated, cation-permeable channels that are assembled in pentamers composed in a variety of subunit combinations (␣2-␣10 and ␤2-␤4; (Dani, 2001;Barik and Wonnacott, 2009), with the ␣4* bearing nAChR being the most prevalent (* indicates that there are other subunits in the pentameric nAChR). Studies have shown that nAChRs can regulate synaptic plasticity in the hippocampus and reward pathways (McKay et al, 2007;Nashmi et al, 2007;Changeux, 2010). In the visual cortex, these receptors are highly expressed during the critical period of ocular dominance plasticity (Prusky et al, 1988), which can be extended by removing a molecular brake on nAChR function (Morishita et al, 2010).…”

Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane

“…7 The nerve terminal is a potential site of action for anaesthetic effects on synaptic transmission. 8 Selective inhibition of depolarization-evoked release of excitatory glutamate vs release of inhibitory GABA from neocortical nerve terminals by clinically relevant concentrations of IAs supports an overall depression of excitatory transmission during anaesthesia.…”