consciousness and motivation: modulatory systems of the

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


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


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


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)


Decarboxylase

Dopamin beta

Hydroxylase

(Noradrenalin)

Phenylethanolamin-

N-methyltransferase(Adrenalin)

Biogenic amines

cocaine

Decreased reuptake of

dopamine, noradrenalin

and serotonin


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


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


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.


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


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


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)


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


(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)


consciousness and motivation: modulatory systems of the

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