Involvement of Nicotinic Receptors in Working Memory Function
The prefrontal cortex underlies our high order cognitive abilities and is the target of projections from many neuromodulatory nuclei. The dorsolateral prefrontal cortex is particularly critical for rule representation and working memory, or the ability to
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Contents 1 Introduction 2 Cholinergic Nuclei and Projections 3 Cholinergic Regulation of Arousal State 4 Acetylcholine in PFC and Attention 5 Acetylcholine in Working Memory 6 Cholinergic Modulation of Cognitive Control 7 Relevance to Disease 8 Conclusion References
Abstract The prefrontal cortex underlies our high order cognitive abilities and is the target of projections from many neuromodulatory nuclei. The dorsolateral prefrontal cortex is particularly critical for rule representation and working memory, or the ability to hold information “in mind” in the absence of sensory input. Emerging evidence supports a prominent and permissive role for acetylcholine in these excitatory circuits, through actions at cholinergic nicotinic receptors. Here we review the involvement of acetylcholine in working memory via actions at nicotinic receptors. Keywords Acetylchoine · Nicotinic receptor · The prefrontal cortex · Working memory
V. C. Galvin, A. F. T. Arnsten, and M. Wang (*) Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA e-mail: [email protected]; [email protected]; [email protected] © Springer Nature Switzerland AG 2020 Curr Topics Behav Neurosci https://doi.org/10.1007/7854_2020_142
V. C. Galvin et al.
1 Introduction The prefrontal cortex (PFC) is the most newly evolved cortical region, showing the greatest expansion across primate evolution, and subserves our higher cognitive functions. The PFC is innervated by many neuromodulators, which act to gate or fine-tune the activity of PFC networks. One of these neuromodulators, acetylcholine (ACh), plays a particularly important role in dorsal PFC areas involved in attention, top down control of actions, and working memory. This chapter will focus on the cholinergic mechanisms influencing the attention, working memory, and rule representation functions of the dorsolateral PFC (dlPFC). All of these functions require the ability to maintain information in mind – e.g., a goal or rule for future actions – and to protect this information from the distraction of intervening events. Recent research shows that cholinergic mechanisms play a key role in these dlPFC functions and provide a physiological link between arousal state and strength of cognitive operations.
2 Cholinergic Nuclei and Projections ACh is synthesized and released in eight primary nuclei in the primate brain. Four of these nuclei reside in the brainstem and midbrain and project to the thalamus, the dopamine-producing midbrain nuclei, interpeduncular brain stem nuclei, and the superior colliculi. Two of these brainstem and midbrain cholinergic nuclei, the pedunculopontine nucleus (PPT) and the laterodorsal tegmental nucleus (LDT), play a critical role in arousal and sleep circuitry, with dense projections to the brainstem reticular formation and to thalamic relay nuclei (Steriade et al. 1990; Steriade et al. 1988; Yeomans 2012). The remaining four cholinergic nuclei comprise the basal forebrain (BF) and project to olfactory bulb, hippocampus, amygdala, and cortex. The four di
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