Enhanced Sensory–Cognitive Processing by Activation of Nicotinic Acetylcholine Receptors

Gil, Susan M; Metherate, Raju

doi:10.1093/ntr/nty134

Cited by 22 publications

(14 citation statements)

References 61 publications

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“…Thus, consistent with previous hypotheses (Hasselmo & McGaughy, 2004), elevation of cortical ACh increases attention to external stimuli, but only under conditions of high attentional demand, including relatively low presentation rates, stimulus unpredictability, or near-threshold psychophysical properties. This supports the idea that the salience of strong emotional memories is due in part to an increase in cortical ACh release: threats and otherwise stressful events are more readily perceived as a result of greater cortical ACh signaling, leading to increased activation of thalamo-cortical afferents (Gil & Metherate, 2019). Since exposure to stress greatly increases cortical ACh release (Mark, Rada, & Shors, 1996;Power & Sah, 2008), the resulting ACh signaling could contribute to increased attention to negative environmental stimuli, thereby facilitating negative encoding bias ( Figure | 117 MINEUR aNd PICCIOTTO 1).…”

Section: Transient Elevation Of Ach Is Important For Attention Butsupporting

confidence: 80%

The role of acetylcholine in negative encoding bias: Too much of a good thing?

Mineur

Picciotto

2019

Eur J of Neuroscience

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Optimal acetylcholine (ACh) signaling is important for sustained attention and facilitates learning and memory. At the same time, human and animal studies have demonstrated increased levels of ACh in the brain during depressive episodes and increased symptoms of anxiety, depression, and reactivity to stress when ACh breakdown is impaired. While it is possible that the neuromodulatory roles of ACh in cognitive and affective processes are distinct, one possibility is that homeostatic levels of ACh signaling are necessary for appropriate learning, but overly high levels of cholinergic signaling promote encoding of stressful events, leading to the negative encoding bias that is a core symptom of depression. In this review, we outline this hypothesis and suggest potential neural pathways and underlying mechanisms that may support a role for ACh signaling in negative encoding bias.

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Section: Transient Elevation Of Ach Is Important For Attention Butsupporting

confidence: 80%

The role of acetylcholine in negative encoding bias: Too much of a good thing?

Mineur

Picciotto

2019

Eur J of Neuroscience

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“…The loss of these receptors from several regions of brains affected by AD is observed in receptor-ligand binding studies, and this loss is positively correlated with the presence of SPs in the temporal lobe ( 26 ). The α (α2-α10) and β (β2-β4) subunits of these receptors combine to form both hetero- and homo-pentameric subtypes, of which α4β2 and α7 nAChRs are the predominant subtypes in human brains ( 27 ). Moreover, neuronal nAChRs are expressed pre-, post- and extra-synaptically in the brains and mediate postsynaptic responses ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Expression levels of the α7 nicotinic acetylcholine receptor in the brains of patients with Alzheimer's disease and their effect on synaptic proteins in SH-SY5Y cells

et al. 2020

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Alzheimer's disease (AD) is a chronic neurodegenerative, and abnormal aggregation of the neurotoxic β amyloid (Aβ) peptide is an early event in AD. The present study aimed to determine the correlation between the nicotinic acetylcholine receptor α7 subunit (α7 nAChR) and Aβ in the brains of patients with AD, and to investigate whether the increased expression levels of the α7 nAChR could alter the neurotoxicity of Aβ. The expression levels of α7 nAChR and Aβ in the brains of patients with AD and healthy brains were analyzed using immunofluorescence. Moreover, SH-SY5Y cells were used to stably overexpress or silence α7 nAChR expression levels, prior to the treatment with or without 1 µmol/l Aβ 1-42 oligomer (AβO). The mRNA and protein expression levels of α7 nAChR, synaptophysin (SYP), postsynaptic density of 95 kDa (PSD-95) and synaptosomal-associated protein of 25 kDa (SNAP-25) were subsequently analyzed using reverse transcription-quantitative PCR and western blotting. In addition, the concentration of acetylcholine (ACh) and the activity of acetylcholinesterase (AChE) were analyzed using spectrophotometry, while the cell apoptotic rate was determined using flow cytometry. The expression of Aβ in the brains of patients with AD was found to be significantly increased, whereas the expression of α7 nAChR was significantly decreased compared with the healthy control group. In vitro , the expression levels of α7 nAChR were significantly increased or decreased following the overexpression or silencing of the gene, respectively. Consistent with these observations, the mRNA and protein expression levels of SYP, PSD-95 and SNAP-25 were also significantly increased following the overexpression of α7 nAChR and decreased following the genetic silencing of the receptor. In untransfected or negative control cells, the expression levels of these factors and the apoptotic rate were significantly reduced following the exposure to AβO, which was found to be attenuated by α7 nAChR overexpression, but potentiated by α7 nAChR RNA silencing. However, no significant differences were observed in either the ACh concentration or AChE activity following transfection. Collectively, these findings suggested that α7 nAChR may protect the brains of patients with AD against Aβ, as α7 nAChR overexpression increased the expression levels of SYP, SNAP-25 and PSD-95, and attenuated the inhibitory effect of Aβ on the expression of these synaptic proteins and cell apoptosis. Overall, this indicated that α7 nAChR may serve an important neuroprotective role in AD.

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“…It is not clear how inhibition of distal dendrites would alter intracortical processing, but the overall result of nicotine's actions may contribute to increased Pyr neuron responsiveness and selectivity to acoustic inputs (Askew et al, ; Intskirveli & Metherate, ). Given the complexity of nAChR‐mediated cellular actions in this and prior studies, a full understanding of nicotinic regulation will require integrating the contributions of diverse nAChRs with varying subunit composition, cellular distribution, and response to agonist (Gil & Metherate, ; Poorthuis et al, ). Overall, nicotinic modulation may serve as a preparatory mechanism for incoming input, resulting in improved cortical processing.…”

Section: Discussionmentioning

confidence: 99%

“…Given the complexity of nAChR-mediated cellular actions in this and prior studies, a full understanding of nicotinic regulation will require integrating the contributions of diverse nAChRs with varying subunit composition, cellular distribution, and response to agonist (Gil & Metherate, 2019;Poorthuis et al, 2013). Overall, nicotinic modulation may serve as a preparatory mechanism for incoming input, resulting in improved cortical processing.…”

Section: Conclusion and Broader Implicationsmentioning

confidence: 94%

“…Nicotine is known to enhance cognitive function and has been shown to improve performance on a variety of attentional, memory, and sensory tasks (Lawrence, Ross, & Stein, ; Levin, McClernon, & Rezvani, ; Rezvani & Levin, ; Swan & Lessov‐Schlaggar, ). Consequently, nicotine may be a promising therapeutic drug for some cognitive or sensory disorders (Gil & Metherate, ; Kumari & Postma, ; Newhouse et al, ). Nicotine acts via nicotinic acetylcholine receptors (nAChR), which are distributed throughout the brain (Clarke, Schwartz, Paul, Pert, & Pert, ; Dani & Bertrand, ).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex

Askew

López

Wood

et al. 2019

Synapse

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Nicotine activates nicotinic acetylcholine receptors and improves cognitive and sensory function, in part by its actions in cortical regions. Physiological studies show that nicotine amplifies stimulus‐evoked responses in sensory cortex, potentially contributing to enhancement of sensory processing. However, the role of specific cell types and circuits in the nicotinic modulation of sensory cortex remains unclear. Here, we performed whole‐cell recordings from pyramidal (Pyr) neurons and inhibitory interneurons expressing parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) in mouse auditory cortex, in vitro. Bath application of nicotine strongly depolarized and excited VIP neurons, weakly depolarized Pyr neurons, and had no effect on the membrane potential of SOM or PV neurons. The use of receptor antagonists showed that nicotine's effects on VIP and Pyr neurons were direct and indirect, respectively. Nicotine also enhanced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in Pyr, VIP, and SOM, but not PV, cells. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we show that chemogenetic inhibition of VIP neurons prevents nicotine's effects on Pyr neurons. Since VIP cells preferentially contact other inhibitory interneurons, we suggest that nicotine drives VIP cell firing to disinhibit Pyr cell somata, potentially making Pyr cells more responsive to auditory stimuli. In parallel, activation of VIP cells also directly inhibits Pyr neurons, likely altering integration of other synaptic inputs. These cellular and synaptic mechanisms likely contribute to nicotine's beneficial effects on cognitive and sensory function.

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Enhanced Sensory–Cognitive Processing by Activation of Nicotinic Acetylcholine Receptors

Cited by 22 publications

References 61 publications

The role of acetylcholine in negative encoding bias: Too much of a good thing?

The role of acetylcholine in negative encoding bias: Too much of a good thing?

Expression levels of the α7 nicotinic acetylcholine receptor in the brains of patients with Alzheimer's disease and their effect on synaptic proteins in SH-SY5Y cells

Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex

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