Nicotinic activity layer specifically modulates synaptic potentiation in the mouse insular cortex

Abstract

Nicotinic acetylcholine receptors (nAChRs) in the insular cortex play an important role in nicotine addiction, but its cellular and synaptic mechanisms underlying nicotine addiction still remain unresolved. In layer 5 pyramidal neurons of the mouse insular cortex, activation of nAChRs suppresses synaptic potentiation through enhancing GABAergic synaptic transmission via activation of β2-containing nAChRs in non-fast-spiking (non-FS) interneurons. However, it has not been addressed whether and how activation of nAChRs modulates synaptic plasticity in layers 3 and 6 pyramidal neurons of the insular cortex. In this study, I demonstrate that activation of nAChRs oppositely modulates synaptic potentiation in layers 3 and 6 pyramidal neurons of the insular cortex. In layer 3 pyramidal neurons, activation of nAChRs depressed synaptic potentiation induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training) through enhancing GABAergic synaptic transmission via activation of β2-containing nAChRs in non-FS interneurons. By contrast, in layer 6 pyramidal neurons, activation of nAChRs enhanced synaptic potentiation through activating postsynaptic β2-containing nAChRs. These results indicate, in different layers of the mouse insular cortex, paired training-induced synaptic potentiation is oppositely regulated by activation of nAChRs which are located on GABAergic interneurons (layer 3) and on pyramidal neurons (layer 6). Thus, layer-specific modulation of synaptic potentiation may be involved in cellular and synaptic mechanisms of insular cortical changes in nicotine addiction.

Layer-Dependent Modulation of Mouse Insular Synaptic Activities by Nicotinic Acetylcholine Receptors

“…In agreement with these findings, most of L3 PCs in the IC (26 of 29 cells, 90%) did not have functional nicotinic receptors ( Figure 1) [21]. Indeed, glutamatergic synaptic transmission in L3 PCs of the IC was not affected by nicotinic receptor activation [21]. In L3 of the IC, an about half of fast-spiking interneurons (6 of 11 cells, 55%) expressed α7 nicotinic receptors and most of non-fast-spiking interneurons expressed α7 and/or β2 nicotinic receptors (α7/β2: 11 of 28 cells; 39%, α7: 5 of 28 cells; 18%, β2: 10 of 28 cells; 36%, Figure 1) [21].…”

“…It has been demonstrated that a majority of L2/3 PCs in the PFC, visual cortex, somatosensory cortex and motor cortex do not have functional nicotinic receptors [14,[18][19][20]. In agreement with these findings, most of L3 PCs in the IC (26 of 29 cells, 90%) did not have functional nicotinic receptors ( Figure 1) [21]. Indeed, glutamatergic synaptic transmission in L3 PCs of the IC was not affected by nicotinic receptor activation [21].…”

“…Indeed, glutamatergic synaptic transmission in L3 PCs of the IC was not affected by nicotinic receptor activation [21]. In L3 of the IC, an about half of fast-spiking interneurons (6 of 11 cells, 55%) expressed α7 nicotinic receptors and most of non-fast-spiking interneurons expressed α7 and/or β2 nicotinic receptors (α7/β2: 11 of 28 cells; 39%, α7: 5 of 28 cells; 18%, β2: 10 of 28 cells; 36%, Figure 1) [21]. These results are comparable to those obtained from L2/3 of the mouse PFC [14,16].…”

Interaction of nicotinic acetylcholine receptors with dopamine receptors in synaptic plasticity of the mouse insular cortex

“…Therefore, the modulation of dopamine and other monoamine release caused by the activation of nAChRs may contribute to the nicotine‐induced inhibition of synaptic potentiation. In the mouse agranular insular cortex, nicotine‐induced modulation of synaptic plasticity is layer‐specific: nicotine suppresses synaptic potentiation in layers 3 and 5 pyramidal neurons while it facilities synaptic potentiation in layer 6 pyramidal neurons (Sato et al, ; Toyoda, ). Thus, future studies would be necessary to demonstrate how the interaction between nAChRs and dopamine receptors modulates synaptic plasticity in layers 3 and 6 pyramidal neurons of the insular cortex.…”

Cholinergic mechanisms in adaptive behaviour

“…); cortex (Torterolo et al . , Toyoda ), hippocampus (Betterton et al . , laterodorsal tegmental nucleus (Taoka et al .…”