Neuromodulatory Systems

· Acetylcholine neuromodulatory system emanates from neurons in pontine brainstem and basal forebrain. (Hobson; Dream Drugstore, 39)

· Noradrenergic neuromodulatory system emanates from several brainstem nuclei including the nucleus locus coeruleus. (Hobson; Dream Drugstore, 40)

· Serotonergic neuromodulatory system emanates from the raphe nuclei, a chain of mid-line and brain stem neuronal clusters. (Hobson; Dream Drugstore, 41)

· Dopaminergic neuromodulatory system emanates from the VTA and substantia nigra. (Hobson; Dream Drugstore, 42)

· Oxytocin social bonding neuropeptide (Preston, Rewarding Nature of Social Contact)

Consciousness is determined by the neurochemical modulatory systems of the brainstem core. (Hobson; Consciousness, 73)

Neurochemical modulatory systems confer a second kind of unity on the brain, a metabolic one, which complements electrical synchrony and activation. (Hobson; Consciousness, 73)

Two types of circuits in the brain. (1) mediating circuits produce behaviors, (2) modulatory circuits act on the mediating circuits, regulating the strength of their synaptic connections. (Kandel; Search of Memory, 224)

Most neurons in the brain are under the influence of as many as a dozen or more neuroactive substances. (Shepherd, Synaptic Organization of the Brain; McCormick; Neurotransmitter Actions, 61)

Two main classes of modulatory neurons: (1) aminergic and (2) cholinergic systems. (Hobson; Consciousness, 73)

Cholinergic neurons are active in REM sleep. (Hobson; Consciousness, 74)

Five well-established biogenic amine neurotransmitters -- three catecholamines -- (1) dopamine, (2) (noradrenaline), (3) epinephrine (adrenaline) -- and (4) histamine and (5) serotonin. (Purves; Neuroscience, 147)

Catecholamines are derived from the amino acid tyrosine. (Purves; Neuroscience, 147)

Dopamine

Dopamine is present in several brain regions, although the major dopamine containing area of the brain is the corpus striatum, which recieves major input from the substantia nigra and plays an essential role in the coordination of body movements. (Purves; Neuroscience, 147)

Dopamine is also involved in motivation, reward, and reinforcement, and many drugs of abuse work by affecting dopaminergic synapses in the CNS. (Purves; Neuroscience, 147)

Human brain has relatively few dopaminergic neurons, equally divided between the substantia nigra and the ventral tegmental area. (Kandel; Principles of Neural Science, 1009)

Dopaminergic neurons send their axons to the nucleus accumbens, the striatum, and the frontal cortex, three structures thought to be involved in motivation. (Kandel; Principles of Neural Science, 1009)

Research study — Dopaminergically Mediated Reward in Somatosensory Decision-Making

Research study — Neurotransmitter Switching Regulates Behavior

Diffusely Projecting Neuromodulatory Neurons

Dopamine System and Pleasure, (Pinel; Anatomy of Human Brain,192

Mesotelencephalic dopamine system, (Pinel; Anatomy of Human Brain,192

Substantia nigra, (Pinel; Anatomy of Human Brain,192

Ventral tegmental area, (Pinel; Anatomy of Human Brain,192

Nucleus accumbens, (Pinel; Anatomy of Human Brain,192

Hypothalamus, (Pinel; Anatomy of Human Brain,194

Raphe nuclei, (Pinel; Anatomy of Human Brain,194

Locus coeruleus, (Pinel; Anatomy of Human Brain,196

Raphe nuclei, (Pinel; Anatomy of Human Brain,196

Research study — Neuromodulatory Systems — Recent Research

Neuromodulatory neurons: (1) relatively few and relatively small, (2) highly localized to a few brain stem nuclei, (3) they are pacemaker cells; rhythmical and spontaneous, (4) fire at relatively low rates, metronome-like, (5) project their fine, multiply branching processes all over the brain and spinal cord. (Hobson; Dreaming, 63)

Noradrenergic locus coeruleus - fan-like 'hairnet' of fibers all over the brain, release neuromodulator noradrenaline. (Edelman; Universe of Consciousness, 43)

Neurotransmitters dopamine, norepinephrine, and serotonin, as well as neuromodulators can also change how we feel about ourselves. (Damasio; Descartes' Error, 160)

Noradrenaline belongs to a family of catecholamines; it is synthesized from dopamine in the brain. Noradrenergic projections from the locus ceruleus in the mammalian brain. (diagram) (Dudai; Memory from A to Z, 178)

Major modulatory systems of the brain

Major modulatory systems of the brain. (1) noradrenergic, (2) adrenergic, (3) dopaminergic, (4) serotonergic, (5) cholinergic, (6) histaminergic. (Kandel; Principles of Neural Science, 890)

Hypothalamus is situated within the cluster of brain cells comprising the amine fountains modulating the activity of higher reaches of the brain. (Greenfield; Private Life of Brain, 175)

Noradrenergic and adrenergic neurons in the medulla and pons. (diagram) (Kandel; Principles of Neural Science, 890)

Adrenergic cell groups (diagram) (Kandel; Principles of Neural Science, 891)

Dopaminergic neurons in the brain stem and hypothalamus (diagram) (Kandel; Principles of Neural Science, 892)

Serotonergic neurons along the midline of the brain stem (diagram) (Kandel; Principles of Neural Science, 893)

Activity in brain stem afferents is associated with more alert behavioral states. (Shepherd; Synaptic Organization of the Brain, 323)

Cholinergic neurons in the upper pontine tegmentum and basal forebrain diffusely innervate much of the brain stem and forebrain. (diagram) (Kandel; Principles of Neural Science, 894)

Histaminergic neurons in the brain are located in the hypothalamus. (diagram) (Kandel; Principles of Neural Science, 895)

The largest collection of noradrenergic neurons is in the pons in the locus ceruleus. (Kandel; Principles of Neural Science, 895)

Histaminergic neurons in the brain are located in the hypothalamus. (diagram) (Kandel; Principles of Neural Science, 895)

Five monoaminergic systems of neurons in the brain stem. (Kandel; Principles of Neural Science, 895)

Each of these six neuronal systems has extensive connections in most areas of the brain and each plays a major role in modulating sensory, motor, and arousal tone. (Kandel; Principles of Neural Science, 895)

Ascending projections from the brain stem modulate arousal and consciousness. (Kandel; Principles of Neural Science, 896)

Ascending arousal system divides into two major branches at the junction of the midbrain and diencephalon. One branch enters the thalamus, where it activates and modulates nuclei with extensive diffuse cortical projections. Other branch travels through the lateral hypothalamus area, joined by other cell groups, all of which diffusely innervate the cerebral cortex. (Kandel; Principles of Neural Science, 897)

Ascending arousal system consist of axons of cell populations in the upper brain stem, hypothalamus, and basal forebrain (diagram) (Kandel; Principles of Neural Science, 900)

Neuromodulators classified as peptides, amines, hormones

Consider three classes of modulators: peptides, amines, and hormones. Each can have excitatory or inhibitory effects, depending on the specifics of their participation in functional circuits. (LeDoux; Synaptic Self, 57)

Dopamine cells in the brain stem modulate all aspects of the circuitry in the prefrontal cortex, enhancing or facilitating the excitation. (LeDoux; Synaptic Self, 190)

Brain stem arousal systems release modulatory monoamines in all areas of the prefrontal cortex. (LeDoux; Synaptic Self, 226)

Prozac may reduce exaggerated fear and anxiety in psychiatric disorders by enhancing the ability of serotonin to facilitate GABA inhibition. (LeDoux; Synaptic Self, 64)

Fear system illustrates the basic elements of neural transmission in the brain and its regulation by modulatory chemicals. (LeDoux; Synaptic Self, 64)

Neuromodulators

(paraphrase from Hobson; Consciousness, 74ff)

The brain's modulatory system provides a uniformity of neurochemical background for each conscious state.

Secreted chemical neuromodulators have a powerful effect on neurons they interact with. All neuromodulators are capable of triggering cascades of chemical events in neurons that control metabolic activity–including protein synthesis.

The widespread projection of neuromodulator neurons to distant parts of the brain assures that the effects of neuromodulation are uniformly dispersed. This chemical neuromodulation, as well as electrical synchrony, serves to unite neurons within and across modular boundaries and unites neurons to operate in a consistent manner in any particular state of consciousness. Thus, in waking, the whole brain could be primed to capture data, while in sleep, those data might be differentially processed (in the NREM and REM states).

The multiplicity of neuromodulatory subsystems. On the aminergic (waking) side, at least four different subsystems are involved: (1) locus coeruleus-based noradrenergic system; (2) raphe nuclei-based serotonergic system; (3) midbrain-based dopaminergic system; (4) hypothalamus-based histaminergic system_. All four appear to energize the brain. How these systems differ from one another is still only partially understood. The noradrenergic and histaminergic systems have been implicated in vigilance, alertness, and attention; the serotonergic system in restraining motor action, helping it to be stimulus- and situation-specific; the dopaminergic system in supporting and facilitating movement, positive emotion, and thought.

The tendency of all the neurons in any modulatory class to behave consistently and in reliable concert in any particular state. For example, during waking, all the neurons of the noradrenergic, serotonergic, and histominergic systems fire slowly and regularly All of them fire more and more slowly in NREM sleep, and all of them stop firing in REM sleep. The coordination of this highly reliable, state-specific pattern appears to be orchestrated by an inhibitory system using GABA, a neurotransmitter that arises in the anterior hypothalamus, where the circadian clock is also located. The only system that does not shut off in REM sleep is the dopaminergic, perhaps to allow motor programs to run offline.

The result of neuromodulatory properties is that consciousness can be differentiated automatically, reliably, and consistently so as to resonate harmoniously in the various consciousness states.

(end of paraphrase)

Attention and Neuromodulators

Reticular system: multiple ascending pathways from subcortical nuclei, each associated with different neurotransmitters and neuromodulators that have different properties and different cortical innervation patterns. (Parasuraman; Varieties of Attention, 227)

Four main projection systems have been identified as playing functional roles in arousal and attention: (1) cholinergic basal forebrain, (2) noradrenergic nucleus locus coerulus (LC), (3) dopaminergic median forebrain bundle, (4) serotonergic dorsal raphe nucleus. (Parasuraman; Varieties of Attention, 227)

In addition to the intralaminar thalamic nuclei, two other thalamic nuclei, the reticular nucleus and the pulvinar, have been implicated in attention and arousal. (Parasuraman; Varieties of Attention, 227)

Hobson’s AIM Model for Sleep

Allan Hobson’s AIM Sleep Model

Edelman’s Value Systems

Frontal cortex connections to basal ganglia and limbic system, establish relations among values and categorizations of sensory experience. (Edelman; Remembered Present, 145)

Primary consciousness results from the interaction in real time between memories of past value-category correlations and present world input as it is categorized by global mappings. (Edelman; Remembered Present, 155)

Brain stem, together with the limbic (hedonic) system concerned with appetite, sexual and sonsummatory behavior, evolved defensive behavior patterns. It is a value system. (Edelman; Bright Air, 117)

Value system is extensively connected to many different body organs, the endocrine system, and the autonomic nervous system. (Edelman; Bright Air, 117)

Value systems regulate heart and respiratory rate, sweating, digestive functions, as well as bodily cycles related to sleep and sex. (Edelman; Bright Air, 117)

Link to — Consciousness Subject Outline