Note: Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Acknowledgements and Disclosures -- Introduction: revision of an old transmitter -- Part I The neurobiology of norepinephrine -- 1 Neuroanatomical and chemical organization of the locus coeruleus -- Early history of the locus coeruleus -- Species comparisons -- Ontogeny -- Morphological and ultrastructural characteristics -- Transmitter identity and receptor distribution -- Classical transmitters -- Neuropeptides -- Connections: sources of afferent input to LC -- Retrograde studies -- Anterograde studies -- Ultrastructural examinations -- The LC efferent projection -- Histochemistry and anterograde labeling -- Retrograde labeling -- Chemoarchitecture: neurochemically identified pathways -- Excitatory inputs -- Inhibitory inputs -- Serotonergic inputs -- Dopaminergic, noradrenergic, and adrenergic inputs -- Neuropeptide inputs -- Enkephalin -- Efferent connections -- Overview -- REFERENCES -- 2 Interactions of norepinephrine with other neurotransmitter systems: anatomical basis and pharmacology -- Introduction -- Noradrenergic circuitry: input to the LC -- Serotonin -- Dopamine -- Aminobutyric acid -- Glutamate -- Acetylcholine -- Substance P -- Noradrenergic circuitry: reciprocal output from the LC -- Summary and conclusions -- Acknowledgements -- REFERENCES -- 3 Receptors for norepinephrine and signal transduction pathways -- Introduction -- Adrenergic receptor subtypes -- Historical development -- Characteristics of alpha1-adrenergic receptors -- Pharmacological characteristics of 1-adrenergic receptors -- Molecular characteristics of alpha1-adrenergic receptors -- Regulation of alpha1-adrenergic receptors -- Characteristics of alpha2-adrenergic receptors -- Pharmacological characteristics of alpha2-adrenergic receptors. , Molecular characteristics of alpha2-adrenergic receptors -- Regulation of alpha2-adrenergic receptors -- Characteristics of beta-adrenergic receptors -- Pharmacological characteristics of beta-adrenergic receptors -- Molecular characteristics of beta-adrenergic receptors -- Regulation of beta-adrenergic receptors -- Signal transduction pathways -- Alpha1-adrenergic receptors -- Alpha2-adrenergic receptors -- Beta-adrenergic receptors -- Physiological roles -- Alpha1-adrenergic receptors -- Alpha2-adrenergic receptors -- Subtype specific functions of Alpha2-adrenergic receptors -- Alpha2-adrenergic receptor polymorphisms -- Beta-adrenergic receptors -- Beta1- and Beta2-adrenergic receptors -- Beta1- and Beta2-adrenergic receptor polymorphisms -- Beta3-adrenergic receptors -- Conclusions/summary -- REFERENCES -- 4 Regulation of gene transcription in the central nervous system by norepinephrine -- Introduction -- Fundamental concepts of gene transcription -- Initiation of gene transcription -- Transcription factors -- Noradrenergic receptors couple to multiple signal transduction cascades and transcription factors -- Noradrenergic receptor regulation of the cAMP-CREB cascade -- Activation of alpha1-adrenergic receptors also leads to up-regulation of CREB-mediated gene transcription -- Noradrenergic receptor regulation of AP-1 family transcription factors -- Role of noradrenergic receptor regulation of transcription factors and gene expression in the actions of antidepressant treatment -- Antidepressant treatment up-regulates the cAMP-CREB cascade -- CREB produces antidepressant effects in behavioral models of depression -- CREB increases neurogenesis in adult hippocampus -- Antidepressants and norepinephrine regulation of c-fos gene expression and AP-1 DNA binding -- Regulation of c-Fos and IEG expression by desipramine. , Regulation of c-Fos by stress/NE -- Role of NE-CREB signaling in learning and memory -- Conclusions -- Acknowledgements -- REFERENCES -- 5 The norepinephrine transporter and regulation of synaptic transmission -- Introduction -- The norepinephrine transporter and the importance of norepinephrine uptake -- Molecular structure of norepinephrine transporters -- Localization of the norepinephrine transporter -- Function of the norepinephrine transporter -- Norepinephrine transporter as a drug target -- Mechanism of norepinephrine uptake -- Regulation of norepinephrine uptake -- Acute regulation of neuronal norepinephrine reuptake -- Chronic regulation of neuronal norepinephrine reuptake -- Norepinephrine transporter-associated proteins -- Norepinephrine transporter gene, polymorphisms and splice variants -- Clearance of norepinephrine and aging -- Norepinephrine transport and disease -- Conclusions -- Acknowledgements -- References -- Part II Norepinephrine and behavior -- 6 Role of the locus coeruleus-norepinephrine system in arousal and circadian regulation of the sleep-wake cycle -- Introduction -- Brain systems involved in sleep-wake regulation -- Waking, slow-wave sleep and paradoxical sleep -- Networks involved in regulation of the sleep-wake cycle -- Neuronal groups -- Mechanisms involved in sleep-waking cycle stage changes -- LC involvement in sleep-wake regulation -- Activity ofLC neurons during sleep and waking -- Tonic LC activity varies with behavioral state -- Primate LC activity during sleep and waking -- LC activity and cortical arousal -- Effects of locus coeruleus lesions on sleep and waking -- Spontaneous Sleep -- Sleep Rebound -- Role of corticotropin-releasing factor in noradrenergic regulation of sleep and waking -- Role of LC in circadian regulation of sleep and waking -- Indirect projection from the SCN to the LC. , Circadian rhythm in LC impulse activity -- LC lesions decrease circadian amplitude of sleep--UnicodeCharacterx2013 waking cycle -- Light deprivation-induced loss of cortical NE -- Clinical perspectives: LC participation in sleep alterations due to clinical pathologies -- Depression -- NE and depression -- Stress, depression, CRF, NE-LC system and sleep -- Sleep deprivation and depression -- Anxiety -- Posttraumatic Stress Disorder ( PTSD ) -- Attention-deficit/hyperactivity disorder (ADHD) -- Aging -- Insomnia -- Conclusions -- REFERENCES -- 7 The locus coeruleus and regulation of behavioral flexibility and attention: clinical implications -- Introduction -- Background -- Global efferent projections -- NE modulates activity of neurons in LC target areas -- Tonic LC activity varies with behavioral state -- LC neurons exhibit polymodal sensory responsiveness -- Recent results recording LC neurons in behaving monkeys -- Target detection task -- Phasic activation of LC neurons by meaningful stimuli -- Fluctuations in tonic LC activity during task performance -- Relationship of tonic to phasic LC activity -- Task difficulty -- Interpretation of results-LC neurophysiology experiments -- Computational modeling: simulation of LC activity and task performance -- Stimulus discrimination network -- LC model -- Electrotonic coupling -- Simulation results -- Interpretation of results: modeling experiments -- Decision-related activation of monkey LC neurons -- Forced-choice task -- Phasic activation of the LC preceded the behavioral response -- Influence of prefrontal cortex on activity of LC neurons -- Discussion -- A new theory of LC function -- Relationship of LC function to attention -- Clinical implications -- Hypertonic LC activity: attention-deficit/hyperactivity disorder and posttraumatic stress disorder -- Attention-deficit hyperactivity disorder (ADHD). , Posttraumatic stress disorder (PTSD) -- Hyperphasic LC activity: autism -- Hypotonic LC activity: depression -- Dysregulated LC phasic activity: schizophrenia -- Loss of LC neurons: dementias of Alzheimer's and Parkinson's diseases -- Sleep disorders -- Regulation of LC mode: implications for new pharmacotherapies -- Acknowledgements -- References -- 8 Norepinephrine and long-term memory function -- Introduction -- Role of adrenergic catecholamines in memory consolidation -- Amphetamine effects on memory consolidation -- Peripheral epinephrine and norepinephrine effects on memory consolidation -- Role of brainstem noradrenergic cell groups in memory consolidation -- Pharmacological and genetic evidence of central norepinephrine in regulating long-term memory consolidation -- Norepinephrine in the amygdala and memory consolidation -- Selective involvement of the basolateral complex of the amygdala -- Stress- and training-induced norepinephrine release in the amygdala and memory consolidation -- Involvement of beta-adrenoceptors and alpha-adrenoceptors in mediating norepinephrine effects on memory consolidation -- Electrophysiological and molecular events in the amygdala induced by noradrenergic activation -- Role of norepinephrine in the amygdala in regulating memory processes in other brain regions -- Interactions of the amygdala noradrenergic system with other neuromodulatory systems on memory consolidation -- Glucocorticoid hormones -- Opioid peptidergic system -- GABA ergic system -- Cholinergic system -- Effects of norepinephrine in other brain regions on memory consolidation -- Hippocampus/entorhinal cortex -- Medial prefrontal cortex -- Insular cortex -- Norepinephrine effects on memory in human subjects -- Summary -- Acknowledgements -- References -- 9 Norepinephrine and stress -- Introduction. , Elevation of tonic noradrenergic neurotransmission with arousal.