Nicotine facilitates long‐term potentiation induction in oriens‐lacunosum moleculare cells via Ca²⁺ entry through non‐α7 nicotinic acetylcholine receptors

Abstract

Hippocampal inhibitory interneurons have a central role in the control of network activity, and excitatory synapses that they receive express Hebbian and anti-Hebbian long-term potentiation (LTP). Because many interneurons in the hippocampus express nicotinic acetylcholine receptors (nAChRs), we explored whether exposure to nicotine promotes LTP induction in these interneurons. We focused on a subset of interneurons in the stratum oriens/alveus that were continuously activated in the presence of nicotine due to the expression of non-desensitizing non-α7 nAChRs. We found that, in addition to α2 subunit mRNAs, these interneurons were consistently positive for somatostatin and neuropeptide Y mRNAs, and showed morphological characteristics of oriens-lacunosum moleculare cells. Activation of non-α7 nAChRs elevated intracellular Ca 2+ levels at least in part via Ca 2+ entry through their channels. Presynaptic tetanic stimulation induced N-methyl-D-aspartate receptor-independent LTP in voltage-clamped interneurons at −70 mV when in the presence, but not absence, of nicotine. Intracellular application of a Ca 2+ chelator blocked LTP induction, suggesting the requirement of Ca 2+ signal for LTP induction. The induction of LTP was still observed in the presence of ryanodine, which inhibits Ca 2+ -induced Ca 2+ release from ryanodine-sensitive intracellular stores, and the L-type Ca 2+ channel blocker nifedipine. These results suggest that Ca 2+ entry through non-α7 nAChR channels is critical for LTP induction. Thus, nicotine affects hippocampal network activity by promoting LTP induction in oriens-lacunosum moleculare cells via continuous activation of non-α7 nAChRs.

Dopamine D1 Receptors Participate in Cocaine-Induced Place Preference via Regulation of Ryanodine Receptor Expression

“…Furthermore, RyRs are linked to nicotine-induced neuronal plasticity (43,45). These data therefore suggest that the changes in RyR function may be an important event linking to neurochemical and behavioral adaptation in association with the alteration of neuronal plasticity occurring in drug abuse.…”

Impaired function of α2-containing nicotinic acetylcholine receptors on oriens-lacunosum moleculare cells causes hippocampus-dependent memory impairments

“…This functional loss of α2* nAChRs is prevented by co-administration of the nAChR antagonist mecamylamine (Chen et al, 2016), suggesting that maternal nicotine-induced nAChR activation rather than desensitization mediates the effect. Because OLM cells are continuously activated in the presence of nicotine due to the non-desensitizing nature of α2* nAChRs (Jia et al, 2009) and α2* nAChR activation triggers Ca 2+ signaling in these cells (Jia et al, 2010), this Ca 2+ could evoke global genomic responses by altering chromatin structures through histone deacetylation and DNA methylation for gene silencing. Therefore, here we investigated the possibility that the functional loss of α2* nAChRs underlies the memory impairment induced by early life nicotine exposure using α2KO mice.…”

Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women

“…In this regard, A allele expression reduces nAChR function leading to reduced intracellular calcium influx following application of a nicotinic agonist (Bierut et al, 2008). This is key as nicotine facilitates long-term potentiation (LTP), the molecular process underlying learning and memory, in a calcium-dependent manner in the hippocampus (Jia et al, 2010), a brain area critically involved in learning and memory (Eichenbaum et al, 2007; Fortin et al, 2004; Poldrack and Packard, 2003). Notably, the hippocampus expresses alpha-5 subunit-containing nAChRs (Wada et al, 1990).…”