Abstract
Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. Alzheimer’s disease (AD) is mainly characterized by progressive dementia and is accompanied by cognitive impairments, including a decline in social ability. The cholinergic system is a potential constituent for the neural mechanisms underlying social behaviour, and impaired social ability in AD may have a cholinergic basis. However, the involvement of cholinergic function in social behaviour has not yet been fully understood. Here, we performed a selective elimination of cholinergic cell groups in the basal forebrain in mice to examine the role of cholinergic function in social interaction and social recognition memory by using the three-chamber test. Elimination of cholinergic neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) caused impairment in social interaction, whereas ablating cholinergic neurons in the nucleus basalis magnocellularis (NBM) impaired social recognition memory. These impairments were restored by treatment with cholinesterase inhibitors, leading to cholinergic system activation. Our findings indicate distinct roles of MS/vDB and NBM cholinergic neurons in social interaction and social recognition memory, suggesting that cholinergic dysfunction may explain social ability deficits associated with AD symptoms.
Highlights
Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory
Our results indicate that medial septum (MS)/vertical diagonal band of Broca (vDB) and nucleus basalis magnocellularis (NBM) cholinergic neurons have important roles in different types of social behaviour, suggesting that deficits in basal forebrain cholinergic systems may explain impairment in social ability related to Alzheimer’s disease (AD) symptoms
Tg mice were generated that carry a chimeric gene encoding human interleukin-2 receptor α-subunit (IL-2Rα) fused to a variant of enhanced yellow fluorescent protein under the control of the gene promoter for choline acetyltransferase (ChAT), and the IL-2Rα/mVenus transgene was expressed in the majority of ChAT-positive neurons in both the MS/vDB and NBM regions of the ChAT-IL-2Rα/mVenus mice, as described in our previous study[20]
Summary
Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. The basal forebrain cholinergic system is comprised of discrete cell groups that innervate a variety of brain regions; neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) provide cholinergic projections predominantly to the hippocampus and the medial prefrontal cortex, and neurons in the nucleus basalis magnocellularis (NBM) provide cholinergic innervations to the entire cortex and basolateral a mygdala[23,24,25,26]. These anatomical findings that cholinergic projection areas overlap with the brain regions required for social. Behaviour indicate the possibility that basal forebrain cholinergic cell groups may be involved in the control of social function through modulation of the activity of the related brain regions
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