Abnormal Social Behavior in Nicotinic Acetylcholine Receptor  4 Subunit-Null Mice

Salas, Ramiro; Fung, Beryl; Biasi, Mariella De

doi:10.1093/ntr/nts215

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…In particular, the lack of β2 nAChR subtype was shown to affect social interaction during aggressive behavior ( Granon et al, 2003 ), an effect likely involving the medial prefrontal cortex (mPFC; Avale et al, 2011 ). The lack of β4 nAChR subunit that is highly expressed in the olfactory bulb and in the lateral habenula ( Salas et al, 2003 ), leads to a decreased interaction between a resident and juvenile intruder mouse ( Salas et al, 2013 ). Furthermore, a single nucleotide polymorphism in the α5 subunit of nAChRs, observed in patients affected by schizophrenia ( Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014 ), leads to deficits in sociability when engineered in mice ( Koukouli et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Pimpinella

Mastrorilli

Giorgi

et al. 2021

eLife

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Acetylcholine (ACh), released in the hippocampus from fibers originating in the medial septum/diagonal band of Broca (MSDB) complex, is crucial for learning and memory. The CA2 region of the hippocampus has received increasing attention in the context of social memory. However, the contribution of ACh to this process remains unclear. Here, we show that in mice, ACh controls social memory. Specifically, MSDB cholinergic neurons inhibition impairs social novelty discrimination, meaning the propensity of a mouse to interact with a novel rather than a familiar conspecific. This effect is mimicked by a selective antagonist of nicotinic AChRs delivered in CA2. Ex vivo recordings from hippocampal slices provide insight into the underlying mechanism, as activation of nAChRs by nicotine increases the excitatory drive to CA2 principal cells via disinhibition. In line with this observation, optogenetic activation of cholinergic neurons in MSDB increases the firing of CA2 principal cells in vivo. These results point to nAChRs as essential players in social novelty discrimination by controlling inhibition in the CA2 region.

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Section: Discussionmentioning

confidence: 99%

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Pimpinella

Mastrorilli

Giorgi

et al. 2021

eLife

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“…Social interactions of PD patients may be affected by disrupted social connectedness (Soleimani et al, 2014); PD patients with mild cognitive deficits showed impairment in social behavior (Anderson et al, 2013). As mentioned, nicotine and other nicotinic agonists activate several nAChR subtypes which are involved in social behavior in monkeys and rodents (Bitner et al, 2010; Boess et al, 2013; Feuerbach et al, 2009; Henderson and Lester, 2015; Salas et al, 2013; Sarter et al, 2009; Timmermann et al, 2012). Chronic nicotine treatment also benefited social behavior in G72Tg mice, a possible mouse model of schizophrenia (Hambsch et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein

Subramaniam

Magen

Bove

et al. 2018

Neurobiology of Disease

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In addition to dopaminergic and motor deficits, patients with Parkinson's disease (PD) suffer from non-motor symptoms, including early cognitive and social impairment, that do not respond well to dopaminergic therapy. Cholinergic deficits may contribute to these problems, but cholinesterase inhibitors have limited efficacy. Mice over-expressing α-synuclein, a protein critically associated with PD, show deficits in cognitive and social interaction tests, as well as a decrease in cortical acetylcholine. We have evaluated the effects of chronic administration of nicotine in mice over-expressing wild type human α-synuclein under the Thy1-promoter (Thy1-aSyn mice). Nicotine was administered subcutaneously by osmotic minipump for 6 months from 2 to 8 months of age at 0.4 mg/kg/h and 2.0 mg/kg/h. The higher dose was toxic in the Thy1-aSyn mice, but the low dose was well tolerated and both doses ameliorated cognitive impairment in Y-maze performance after 5 months of treatment. In a separate cohort of Thy1-aSyn mice, nicotine was administered at the lower dose for one month beginning at 5 months of age. This treatment partially eliminated the cognitive deficit in novel object recognition and social impairment. In contrast, chronic nicotine did not improve motor deficits after 2, 4 or 6 months of treatment, nor modified α-synuclein aggregation, tyrosine hydroxylase immunostaining, synaptic and dendritic markers, or microglial activation in Thy1-aSyn mice. These results suggest that cognitive and social impairment in synucleinopathies like PD may result from deficits in cholinergic neurotransmission and may benefit from chronic administration of nicotinic agonists.

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“…In the PFC, nicotinic ACh receptors (nAChRs) have been described to play important roles in the modulation of social behaviours (Avale et al, 2011; Coura et al, 2013; Granon et al, 2003; Salas et al, 2013). Cholinergic signalling in the striatum has also been suggested to participate in the modulation of social preference (Karvat & Kimchi, 2014; Rapanelli et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Despite deficits in social memory and social preference being a significant health problem and burden on society, the role of neurochemical pathways in social behaviour is poorly understood. The central cholinergic system has been suggested to contribute to the regulation of social behaviour (Coura et al, 2013;Karvat & Kimchi, 2014;Lewis et al, 2015;Mineur et al, 2013;Prado et al, 2006;Salas et al, 2013;Van Kampen et al, 2004;Winslow & Camacho, 1995). Mice with decreased levels of acetylcholine (ACh) in the brain show decreased social interaction and impaired social memory, and these deficits can be relieved using acetylcholinesterase inhibitors (Prado et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Cholinergic transmission from the basal forebrain modulates social memory in male mice

Kljakic

Al‐Onaizi

Janickova

et al. 2021

Eur J of Neuroscience

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Disruptions in social behaviour are prevalent in many neuropsychiatric disorders such as schizophrenia, bipolar disorder and autism spectrum disorders. However, the underlying neurochemical regulation of social behaviour is still not well understood. The central cholinergic system has been proposed to contribute to the regulation of social behaviour. For instance, decreased global levels of acetylcholine release in the brain leads to decreased social interaction and an impairment of social memory in mice. Nonetheless, it has been difficult to ascertain the specific brain areas where cholinergic signalling influences social preference and social memory. In this study, we investigated the impact of different forebrain cholinergic regions on social behaviour by examining mouse lines that differ in their regional expression level of the vesicular acetylcholine transporter—the protein that regulates acetylcholine secretion. We found that when cholinergic signalling is highly disrupted in the striatum, hippocampus, cortex and amygdala mice have intact social preference but are impaired in social memory, as they cannot remember a familiar conspecific nor recognize a novel one. A similar pattern emerges when acetylcholine release is disrupted mainly in the striatum, cortex, and amygdala; however, the ability to recognize novel conspecifics is retained. In contrast, cholinergic signalling of the striatum and amygdala does not appear to significantly contribute to the modulation of social memory and social preference. Furthermore, we demonstrated that increasing global cholinergic tone does not increase social behaviours. Together, these data suggest that cholinergic transmission from the hippocampus and cortex are important for regulating social memory.

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Abnormal Social Behavior in Nicotinic Acetylcholine Receptor 4 Subunit-Null Mice

Cited by 7 publications

References 27 publications

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein

Cholinergic transmission from the basal forebrain modulates social memory in male mice

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