Consciousness and motivation:
Modulatory systems of the brain stem
1. Consciousness
2. The ascending arousal system
- acetylcholine
- biogenic amines (dopamine,
norepinephrine,
epinephrine, serotonin,
histamine)
3. Motivation: The reward system of
the brain
4. Participation of biogenic amines
in systemic diseases
Lesions with complete loss of consciousness: coma
Patients who cannot make a purposeful response to stimulation
Persistent vegetative state: wake-sleep cycle after 1-2 weeks of coma -
appear wakeful, smile etc., but actions have no cognitive content
→ brain death: all brain function cease (but may have responses on
spinal cord level)
Mainly two reasons:
• bilateral impairment of cerebral hemispheres, e.g., caused by a
diffuse metabolic block (hypoxia – inadequate oxygenation; ischemia – insufficient blood flow)
• lesions in the brain stem: ascending arousal (modulatory) system
Barbiturate-induced coma: Protection of brain during major surgery by
reducing metabolic rate of brain tissue
Consciousness
Integrating system for the coordination of brain activity
Consists of relatively few neurons (few thousands) that are concentrated
in specific nuclei and which establish far reaching and diffuse
projections
Individual neurons can modulate up to 100,000 postsynaptic neurons
Characterized by specific types of neurotransmitters
The ascending arousal system
General role:
- Coordination of autonomous functions
- Arousal system
- Modulation of pain
- Control of emotional behavior and mood
Typical neurotransmitters:
- Acetylcholine
- Biogenic amines (dopamine, norepinephrine, epinephrine, serotonin,
histamine)
Acetylcholine:
Key enzyme: Cholin-Acetyltransferase
Transmitter of motoneurons
Transmitter of all pre-ganglionic neurons of the autonomous nervous
system and post-ganglionic neurons of the Parasympathicus
Transmitter in many projections of the brain stem
Acetylcholinesterase
Soman
The ascending arousal system
Acetylcholinesterase
Donepezil
Acetylcholine:
Key enzyme: Cholin-Acetyltransferase
Transmitter of motoneurons
Transmitter of all pre-ganglionic neurons of the autonomous nervous
system and post-ganglionic neurons of the Parasympathicus
Transmitter in many projections of the brain stem
The ascending arousal system
Cholinergic system
Many cholinergic neurons project from nuclei in the basal telencephalon and from
nuclei of the brain stem.
The brain stem nuclei strongly innervate the thalamus.
Basal nuclei innervate large regions of the neocortex and the limbic system (e.g.,
hippocampus).
Role in controlling general brain activity (arousal system) and wake/sleep states
The ascending arousal system
Oxidase
Biogenic amines
- Katecholamines (dopamine, norepinephrine (Noradrenalin),
epinephrine (Adrenalin))
- Serotonin (5-hydroxytryptamin; 5-HT)
- Histamine
Katecholamine: contain 3,4-dihydroxybenzol,
derived from tyrosine
L-DOPA (L-Dihydroxyphenylalanine)
The ascending arousal system
Decarboxylase
Dopamin beta
Hydroxylase
(Noradrenalin)
Phenylethanolamin-
N-methyltransferase(Adrenalin)
Biogenic amines
cocaine
Decreased reuptake of
dopamine, noradrenalin
and serotonin
The ascending arousal system
Serotonin: derived from tryptophane
Oxidase Decarboxylase
Histamine: derived from histidine
Decarboxylase
Agonist of serotonin
and dopamine
receptors
(Wacker et al.,
Cell 2017)
LSD
Increased release of
serotonin and
dopamine
The ascending arousal system
Noradrenergic system
Most noradrenergic neurons are localized in Locus coeruleus.
L.c. is a small nucleus in the pons that consists of about 12,000 neurons.
Axonal projections of the L.c. are highly branched and project in almost every brain
region.
Synaptic endings are not directed but release noradrenaline in large postsynaptic
areas.
Evidence for overactivity of the noradrenergic system in mania (manic overactivity)
from pharmacological studies
The ascending arousal system
May have an important role in controlling general brain activity (arousal system)
→ considered as „Sympathicus of the CNS“
Serotonergic neurons
Most serotonergic neurons are localized in the nine Raphe nuclei of the brain stem.
Serotonergic neurons project in almost every brain region.
Serotonergic neurons modulate arousal, emotional state and sleep cycles.
Neurons of myelencephalic Raphe nuclei project in the spinal cord and modulate
ascending pain transmission.
In primates: Serotonin inhibits aggressive behavior and increases social behavior.
In monkeys with well functioning social behavior: number of serotonin-2 receptors in
the amygdala and some other brain regions is increased.
The ascending arousal system
Evidence for participation of the serotonin-reuptake system in depression
Antidepressant drug „Prozac“ (in German: Fluctin) inhibits re-uptake of serotonin and
increases its availability
Serotonergic neurons
The ascending arousal system
Many dopaminergic neurons in Substantia nigra that innervate striatum
→ control of the extrapyramidal system
→ Degeneration leads to Parkinson‘s disease which is characterized by loss of
motor function
Therapy: Administration of L-DOPA
(precursor of dopamine) Decarboxylase
Dopaminergic system – Substantia nigra
The ascending arousal system
Many dopaminergic neurons in Ventral tegmentum that innervate in a very diffuse
manner the frontal cortex and the limbic system – involved in emotions
(„primary“ and „secondary“ emotions)
Dopaminergic system – ventral tegmentum
„Reward system“ of the brain
Self-stimulation of the ventral tegmentum is preferred over other regions in
animals and patients
„Reward system“ is activated after input that comprises a reward or signals an
upcoming reward (counterpart of „fear“ after stimulation of the amygdala)
The ascending arousal system
Ventral
tegmentumNucleus
accumbens
Opioid signal
Amygdala Hippocampus
EC
The „reward system“ of the brain
Central part: dopaminergic
neurons, which project into
the Nucleus accumbens
(limbic system), where a
dopamine-signal is translated
into an opioid signal
Motivation
(„The Scientist“, 21(6):52(2007))
Permanent changes in the
Nucleus accumbens during
addiction
→ Probably cause for high rate of
relapse
The „reward system“
Central part: dopaminergic
neurons, which project into
the Nucleus accumbens
(limbic system), where a
dopamine-signal is translated
into an opioid signal
Motivation
Psychotic diseases
prevalence: about 1%
genetic component
Sometimes associated with persecution mania
(Verfolgungswahn)
Schizophrenia
Participation of biogenic amines in systemic diseases
John Forbes Nash Jr.
(US-american mathematician, 1994 Nobel
prize for economy (game theory))
Schizophrenia
Dopamine system appears to be at least partially involved:
➢ Pharmacological treatment that decreases dopaminergic synaptic
transmission (e.g., antipsychotic drug haloperidol) improves state of
schizophrenic patients
➢ Drugs that increase dopamine concentration (L-DOPA and cocaine) lead to
Schizophrenia-like symptoms
➢ postmortem analysis revealed an increased number of dopaminergic
receptors in the limbic system
New generation of antipsychotic drugs revealed, that also high affinity binding to
serotonin 2A receptors occurs
Participation of biogenic amines in systemic diseases
(Unipolar) depression: unpleasant mood, inability to experience pleasure,
generalized loss of interest in the world
– potential life threatening: 15% of all patients with depression die from suicide
Bipolar depressive (manic depressive) disorders: alternating euphoria and
depression
Participation of serotonin (and other biogenic amines) in
mood disorders (disorders of affect)
Evidence for participation of the serotonin-reuptake system in depression
Antidepressant drug „Prozac“ (in German: Fluctin) inhibits re-uptake of serotonin and
increases its availability
Genetic factors are important – appears to be polygenic (no specific gene yet
identified)
Participation of biogenic amines in systemic diseases
