Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Neurotransmitters

Neurotransmitter molecules diffusing across synaptic space between neurons mediate the transmission of information in the neural network. Much neural network functionality is performed via neurotransmitters in the synapses.

Approximately 100 substances function as neurotransmitters, each of which can activate several different receptors on the cell surface. (Kandel; Principles of Neural Science, 230)

Six best-known neurotransmitters -- glutamate, GABA, norepinephrine, dopamine, serotonin, and acetylcholine. (Fuster; Prefrontal Cortex, 65)

Direct gating of ion channels through the ionotropic receptors is usually rapid -- on the order of milliseconds -- because it involves a change in the conformation of only a single macromolecule. (Kandel; Principles of Neural Science, 240)

Transmitter release is triggered by calcium influx. (Kandel; Principles of Neural Science, 255)

Transmitter gated channels produce the fastest and briefest type of synaptic action, lasting only a few milliseconds, on average. (Kandel; Principles of Neural Science, 250)

 

Link to — Biosynthesis of Some Neurotransmitters from Amino Acids

 

Second Messenger actions serve as Modulators

Indirect gating of ion channels through metabotropic receptors is slower in onset (tens of milliseconds to seconds) and longer lasting (seconds to minutes) because it involves a cascade of reactions. (Kandel; Principles of Neural Science, 240)

Many second messenger actions depend on activation of protein kinases, leading to phosphorylation of a variety of cellular proteins, including ion channels, which changes their functional state. (Kandel; Principles of Neural Science, 251)

Second messenger actions do not mediate rapid behaviors but rather serve to modulate the strength and efficacy of fast synaptic transmission -- by modulating: (1) transmitter release, (2) sensitivity of ionotropic receptors, or (3) electrical excitability of the postsynaptic cell. (Kandel; Principles of Neural Science, 251)

Second messengers  trigger a biochemical cascade, either by activating specific protein kinases that phosphorylate a variety of the cell's proteins or by mobilizing calcium ions from intracellular stores. (Kandel; Principles of Neural Science, 229)

Second messenger actions are implicated in emotional states, mood, arousal, and certain forms of learning and memory. (Kandel; Principles of Neural Science, 251)

Longest Lasting Changes in Synaptic Transmission involve Gene Transcription

Longest lasting changes in synaptic transmission involve changes in gene transcription, changes that can persist for days or weeks. (Kandel; Principles of Neural Science, 251)

 

Research study —  Neurotransmitter Switching Regulates Behavior

 

Neurotransmitters and Neuromodulators

Neuroactive substances in the nervous system have been classified as either 'neurotransmitters' are 'neuromodulators' according to the duration and functional implications of their actions. (Shepherd; Synaptic Organization of the Brain, 60)

Substances released in neurotransmitter roles cause postsynaptic responses that are both quick in onset (<1 msec) and relatively short in duration (tens of msec). (Shepherd; Synaptic Organization of the Brain, 61)

Substance released in a neuromodulatory role are characterized by prolonged duration and the ability to modulate the response of the neuron to other inputs. (Shepherd; Synaptic Organization of the Brain, 61)

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

Two major neurotransmitters: glutamate and GABA; released from different presynaptic neurons, bind to distinct postsynaptic receptors; glutamate excitatory, GABA inhibitory. (LeDoux; Synaptic Self, 54)

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)

Neurotransmitters (Squire; Fundamental Neuroscience, 163)

 

Fast-acting neurotransmitters

Neurotransmitters mediating the rapid flow of information are released from pre-synaptic terminals of one neuron and diffused in a millisecond or so to the post-synaptic receptor of another neuron.

Two common fast-acting neurotransmitters: excitatory (ACh) and inhibitory (GABA) (Shepherd; Synaptic Organization of the Brain, 32)

Glutamate is a ubiquitous excitatory transmitter in the brain. (LeDoux; Synaptic Self, 53)

GABA (an amino acid) is a neurotransmitter of inhibitory neurons. (LeDoux; Synaptic Self, 53)

Glutamate and GABA are fast-acting; they cause an electrical change in the postsynaptic cell within milliseconds of being released from the presynaptic terminal, and their effect is over in a matter of milliseconds. (LeDoux; Synaptic Self, 57)

Neurotransmitters acting as modulators have slower and longer-lasting effects. (LeDoux; Synaptic Self, 57)

Glutamate receptors, several types including: AMPA receptor - regular synaptic transmission; NMDA receptor - synaptic plasticity. Neurotransmitters acting as modulators have slower and longer-lasting effects. (LeDoux; Synaptic Self, 144)

 

Modulator neurotransmitters

Modulatory neurotransmitters, operating in seconds, minutes or longer, often emanate from widely-projecting neurons clustered in sub-cortical ganglia. Chemical and functional changes in the synapses of neurons provide many of the short-term and longer-term changes such as memory in the brain function of neural networks.

The four neurotransmitters (norepinephrine, dopamine, serotonin, acetylcholine) originate in nuclear formations of the brain stem and project to orbitomedial and lateral prefrontal cortex. (Fuster; Prefrontal Cortex, 65)

Excitatory and Inhibitory neurons

Excitatory – Glutamate

Inhibitory – GABA (an amino acid)

Inhibitory activity to maintain a resting steady-state is a frequent theme in the neural network. In the basal ganglia, inhibitory activity suppresses FAPs, which always stand ready to initiate movement. To effect a movement commanded by the motor cortex, an excitatory signal stimulates an inhibitory path that inhibits the resting steady-state inhibitory activity. The result is that body movement can respond quickly, jack-in-the-box fashion, but dampened appropriately by the cerebellum.

Two major neurotransmitters: glutamate and GABA; released from different presynaptic neurons, bind to distinct postsynaptic receptors; glutamate excitatory, GABA inhibitory (LeDoux; Synaptic Self, 54)

Glutamate is a ubiquitous excitatory transmitter in the brain. (LeDoux; Synaptic Self, 53)

GABA (an amino acid) is a neurotransmitter of inhibitory neurons. (LeDoux; Synaptic Self, 53)

Glutamate and GABA are fast-acting; they cause an electrical change in the postsynaptic cell within milliseconds of being released from the presynaptic terminal, and their effect is over in a matter of milliseconds. (LeDoux; Synaptic Self, 57)

The majority of the circulating spikes in the dynamic core are mediated by glutamate and GABA neurotransmitters in synapses.

Neurotransmitters are manufactured in cell bodies and transported down the axon to the terminal region where they are used to communicate across synapses. (LeDoux; Emotional Brain, 154)

A neuron receives many excitatory and inhibitory inputs form many other cells; the likelihood of firing at any one moment depends on the net balance between excitation and inhibition across all of the inputs at that particular time. (LeDoux; Synaptic Self, 55)

Modulator neurotransmitters

Neurotransmitters acting as modulators have slower and longer-lasting effects. (LeDoux; Synaptic Self, 57)

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)

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

Peptides as modulators

Peptides represent a large class of slow-acting modulatory substances found throughout the brain. Made up of many amino acids, and are larger molecules than simple amino acids like glutamate and GABA. (LeDoux; Synaptic Self, 57)

Peptides typically have slow modulatory actions. They can dramatically affect the ability of a cell to be fired by other inputs, but cannot do so with precise timing. (LeDoux; Synaptic Self, 58)

"Jogger's high" is said to be an opiate effect. (LeDoux; Synaptic Self, 58)

Oxytocin and vasopressin, both peptides, are molecules released under the control of the hypothalamic nuclei with the help of the posterior pituitary gland. (Damasio; Looking for Spinoza, 62)

Monoamines

Monoamines are a class of modulators that include substances such as serotonin,    dopamine,    epinephrine,   and norepinephrine. (LeDoux; Synaptic Self, 58)

Behaviors experienced as rewarding and pleasurable depend on the release of dopamine from the ventral tegmental area (VTA) in the brainstem and its availability in the nucleus accumbens in the basal forebrain. (Damasio; Looking for Spinoza, 63)

Dopamine levels rise in the nucleus accumbens in response to natural rewards (food, water, and sexual stimuli), and conditioned incentives (stimuli associated with rewards). (LeDoux; Synaptic Self, 247)

 

Research study — Dopamine in Stimulus–Reward Learning

 

Cells that produce monoamines are found in only a few areas, mostly in the brain stem. (LeDoux; Synaptic Self, 58)

Monoamines achieve their effects by facilitating or inhibiting the actions of glutamate or GABA. (LeDoux; Synaptic Self, 58)

Many drugs used in the treatment of psychiatric disorders work by altering monoamines. (LeDoux; Synaptic Self, 58)

Prozac prevents the removal of serotonin from the synaptic space. (LeDoux; Synaptic Self, 58)

Amines are targets of recreational drugs: cocaine and amphetamine affect norepinephrine and dopamine levels, while LSD acts on serotonin receptors. (LeDoux; Synaptic Self, 58)

Diffuse projections of brain stem monoamine cells to forebrain areas - (diagram) (LeDoux; Synaptic Self, 59)

Hormones as modulators

Hormones are a class of modulators released from body organs such as the adrenal, pituitary, or sex glands. (LeDoux; Synaptic Self, 59)

Hormones influence the brain - (diagram) (LeDoux; Synaptic Self, 60)

 

Neurotransmitters classified as small molecule and small protein

Two broad classes of neurotransmitters: (1) small molecule, (2) small protein. (Zeman; Consciousness, 69)

Approximately 10 'small molecule' neurotransmitters. Most are amino acids, or are derived from amino acids: acetylcholine, dopamine, adrenaline, serotonin, histamine; glutamate, glycine, GABA. (Zeman; Consciousness, 70)

Small protein neurotransmitters: endorphins act to modulate the perception of pain; opium and its derivatives mimic the action of the endorphins. (Zeman; Consciousness, 70)

Substances that mimic, oppose, boost or otherwise modify the action of neurotransmitters are among the most widely used drugs in medicine; epilepsy, schizophrenia, depression, Parkinson's disease. (Zeman; Consciousness, 70)

 

 

Modulator neurotransmitters

Small collections of neurons can deliver a dose of dopamine, norepinephrine, serotonin or acetylcholine to widespread regions of the brain including the cerebral cortex and basal ganglia. (Crick 103) (Damasio 120) (Neuroscience 129) (Changeux 34)

All the drugs that are used to treat psychoses have a role on the neuromodulators. (Hobson; Dreaming as Delirium, 67)

Antianxiety drugs such as Valium work by enhancing GABA's natural ability to regulate glutamate. (LeDoux; Synaptic Self, 56)

 

Chemicals involved in emotions and moods are not enough to explain how we feel. Endorphins are the brains own morphine and can change how we feel about ourselves. Neurotransmitters dopamine, norepinephrine, and serotonin, as well as neuromodulators can also change how we feel about ourselves. (Damasio; Descartes' Error, 160)

Aminergis systems support fight and flight responses, vasoconstriction, and direct flow to the muscles. Cholinergic systems promote rest and recovery. Aminergic and cholinergic neuromodulatory neurons in the subcortical brain. (Drugstore 65)

A number of different systems contribute to arousal; four are located in the brainstem. Neurotransmitters: (1) acetylcholine (Ach), (2) noradrenaline, (3) dopamine, (4) serotonin. (Emotional 288)

Neurons of the brain stem that project to the cortex use transmitters such as serotonin, norepinephrine, and dopamine. Other neurons in the brain use acetylcholine. (Crick 103)

Substances that mimic, oppose, boost or otherwise modify the action of neurotransmitters are among the most widely used drugs in medicine; epilepsy, schizophrenia, depression, Parkinson's disease. (Zeman 70)

From yet lower nuclei located in the brain stem (meaning the pons and medulla): tegmentum, locus coeruleus, raphe nuclei, pendulo-pontine nuclei, all involved in neuromodulator production;

Communicate

Milliseconds

LTP (Neil’s 108)

Modulate

Seconds, minutes

Neurotransmitters and their Receptors (Neuroscience 129)

Neural processing of emotions, limbic system, interconnected subcortical regions around the hypothalamus; pleasure pathway, releases dopamine onto the nucleus accumbens. (Feel 119)

Release of dopamine onto the nucleus accumbens appears to underlie all reward feelings. (Feel 116)

Dopamine potently augments the drive to obtain a rewarding stimulus, but it is not directly responsible for the hedonic experience itself. (Nature, Vol 443, 21 September 2006, p.289)

 

A good reference for neurotransmitters. (Purves, Neuroscience, 129)

 

 

Return to — Neuromodulatory Systems

Link to — Consciousness Subject Outline

Further discussion — Covington Theory of Consciousness