Behavioral Pharmacology of the Cholinergic System

Preface
Contents
A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders
	1 Cholinergic System Overview
		1.1 Acetylcholine
		1.2 Muscarinic ACh Receptors (mAChRs)
		1.3 Nicotinic ACh Receptors (nAChRs)
	2 Localization of AChRs in the Central Nervous System
		2.1 mAChRs
		2.2 nAChRs
	3 nAChR Neuronal Expression and Neurotransmission
		3.1 Ionic Selectivity and Ca2+ Permeability
		3.2 Voltage Dependence
	4 Synaptic Plasticity
	5 Intracellular Signaling
		5.1 mAChRs
		5.2 nAChRs
	6 Receptor Desensitization
		6.1 mAChRs
		6.2 nAChRs
	7 Areas of Continued Investigation
	8 Cholinergic Receptors as Therapeutic Targets
		8.1 mAChRs
		8.2 nAChRs
	References
Acetylcholine and Spontaneous Recognition Memory in Rodents and Primates
	1 A Content-Based Approach to Episodic Memory
	2 The Role of Acetylcholine in What-Where-Which Occasion Memory
	3 Differential Roles of Acetylcholine in the Hippocampus and Perirhinal Cortex
	4 Does the What-Where-Which Task Measure Episodic Memory?
	5 The Role of Acetylcholine in Encoding and Retrieval
	References
Endogenous Acetylcholine and Its Modulation of Cortical Microcircuits to Enhance Cognition
	1 Introduction
	2 Anatomy of the Cholinergic System in Prefrontal and Sensory Cortices
		2.1 Cholinergic Innervation of Cerebral Cortex
		2.2 Cortical Cholinergic Synapses
	3 Regulation of Cortical Neurons by Endogenous Acetylcholine
	4 Behavioral Consequences of Endogenous Acetylcholine Release in Cerebral Cortex
	5 Conclusions and Directions for Future Research
	References
Cholinergic Signaling Dynamics and Cognitive Control of Attention
	1 Introduction
	2 Cortical ACh and Attentional Performance
	3 Prefrontal Cholinergic Mechanisms of Signal Detection and Attentional Control
		3.1 Phasic ACh Release Mediates Cue Detection
		3.2 Top-Down Control of Attention and Cholinergic Neuromodulation
	4 Cellular Regulation of Cholinergic Signaling Modes
		4.1 High-Affinity Choline Transporters (CHTs)
		4.2 nAChRs
		4.3 mAChRs
	5 Sex Differences and the Cholinergic Mediation of Attention
		5.1 Neurochemical Sex Differences
		5.2 Behavioral Sex Differences
	6 Conclusions
	References
Involvement of Nicotinic Receptors in Working Memory Function
	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
Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models
	1 Introduction
	2 nAChR Function and Signaling
	3 nAChRs Mediating Nicotine Reinforcement
		3.1 Mesolimbic Pathway
		3.2 Habenulo-Interpeduncular Pathway
	4 nAChRs in Other Aspects of Nicotine Dependence
		4.1 Nicotine Enhancement of Cue Association
		4.2 Nicotine Withdrawal
	5 Modulators of nAChRs Influencing Expression and Function
	6 Beyond Nicotine Dependence
	7 Conclusions
	References
Cholinergic Receptors and Addiction
	1 Addiction
	2 Neuronal Nicotinic Receptors
	3 Special Significance of β2-Containing nAChRs
	4 Special Significance of α5-Containing Receptors
	5 α5 Knockout and Knock-In
	6 Unique Contributions of α7-Containing Receptors
	7 Special Considerations Related to α7 nAChR
	8 Pharmacotherapies for Smoking Cessations
		8.1 Areca: Another Cholinergic-Based Addiction?
	References
Behavioral and Molecular Basis of Cholinergic Modulation of Pain: Focus on Nicotinic Acetylcholine Receptors
	1 Introduction
	2 nAChRs in Pain Modulation
	3 The α4β2 nAChRs in Pain Modulation
	4 The α7 nAChRs in Pain Modulation
	5 The α9/α9α10 nAChRs in Pain Modulation
	6 Conclusions
	References
An Evolving Therapeutic Rationale for Targeting the α7 Nicotinic Acetylcholine Receptor in Autism Spectrum Disorder
	1 Introduction
	2 Structure, Physiology, and Subtypes of Nicotinic Receptors
	3 Allosteric and Other Endogenous Modulators of Nicotinic Receptors
	4 Nicotinic Receptor-Mediated Regulation of GABAergic Interneurons
	5 15q13.3 Copy Number Variants, α7 Nicotinic Acetylcholine Receptors, and the Pathogenesis of Neurodevelopmental Disorders
	6 Nicotinic Receptors and Autism
		6.1 Histochemical, Receptor Binding, Gene Expression, and Electrophysiological Studies
		6.2 Behavioral and Pharmacological Studies
		6.3 Clinical Studies
	7 Conclusion
	References
Activators of α7 nAChR as Potential Therapeutics for Cognitive Impairment
	1 Introduction
		1.1 Structure and Function of α7 nAChR
		1.2 Expression and Localization of α7 nAChR
		1.3 Therapeutic Potential of α7 nAChR Ligands
			1.3.1 Alzheimer´s Disease
			1.3.2 Schizophrenia
	2 α7 nAChR Ligands: Chemical and In Vitro Characterization
		2.1 α7 nAChR Agonists
			2.1.1 GTS-21
			2.1.2 PNU-282987
			2.1.3 RG3487
			2.1.4 TC-5619
			2.1.5 Encenicline
			2.1.6 ABT-107
			2.1.7 ABT-126
			2.1.8 AZD0328
			2.1.9 BMS-933043
		2.2 α7 nAChR Positive Allosteric Modulators
			2.2.1 PNU-120596
			2.2.2 NS1738
			2.2.3 AVL-3288
			2.2.4 TQS
			2.2.5 JNJ-1930942
			2.2.6 JNJ-39393406
			2.2.7 A-867744
			2.2.8 RO5126946
			2.2.9 Lu AF58801
			2.2.10 BNC375
			2.2.11 B-973
			2.2.12 LND101001
	3 α7 nAChR Ligands: In Vivo and Clinical Characterization
		3.1 α7 nAChR Agonists
			3.1.1 GTS-21
			3.1.2 Encenicline
			3.1.3 RG3487
			3.1.4 ABT-126
			3.1.5 TC-5619
		3.2 α7 nAChR PAMs
			3.2.1 AVL-3288
			3.2.2 JNJ-39393406
			3.2.3 LND101001
	4 Conclusions
	References