Function of the midbrain, Function of the midbrain, basal ganglia and thalamusbasal ganglia and thalamus

Romana Šlamberová, MD Romana Šlamberová, MD PhDPhD

Department of Normal, Pathological and Clinical

Physiology

IntroductionIntroduction

Slides from the lecture. Respecting the copyrights it was not

possible to publish pictures showed at the lecture at our website.

© 2007, Romana Slamberova, MD PhD

Midbrain (1)Midbrain (1)

Mesencephalon (or midbrain) is the middle of three vesicles that arise from the neural tube that forms the brain of developing animals.

Caudally the mesencephalon adjoins the pons and rostrally it

The mesencephalon is considered part of the brain stem.

Its substantia nigra is closely associated with motor system pathways of the basal ganglia.

Dopamine produced in the substantia nigra plays a role in motivation and habituation of species from humans to the most elementary animals such as insects.

Midbrain (2)Midbrain (2)

As a mnemonic the mesencephalic cross-section resembles a bear (or teddybear) upside down with the two red nuclei as the eyes and the crus cerebri as the ears.

tectum inferior colliculi superior colliculi

cerebral peduncle midbrain tegmentum crus cerebri substantia nigra

Midbrain (3)Midbrain (3)

On the posterior (back) surface are located the superior colliculus and the inferior colliculus. The superior colliculus - involved with saccadic eye

movements The inferior colliculus - a synapsing point for sound

information On the anterior surface the cerebral peduncles

are prominent. These contain

the corticospinal tract fibres (from the internal capsule) the substantia nigra

Between the peduncles is the interpeduncular fossa, which is a cistern filled with cerebrospinal fluid.

TTectumectum

The tectum (Latin: roof) is the dorsal part of the midbrain and has two parts – superior and inferior colliculi that form the eminences of the corpora quadrigemina.

The superior colliculus is involved in preliminary visual processing, and control of eye movements. It projects to lateral geniculate nucleus of the thalamus.

The superior colliculus (SC) is involved in the generation of saccadic eye movements and eye-head coordination. The SC can also mediate some oculomotor movements without cortical involvement.

The inferior colliculus is involved in auditory processing. It receives input from various brainstem nuclei and projects to the medial geniculate nucleus of the thalamus, which relays auditory information to the primary auditory cortex.

The inferior colliculus is the principal midbrain nucleus of the auditory pathway and receives input from several more peripheral brainstem nuclei in the auditory pathway, as well as inputs from the auditory cortex.

Cerebral peduncleCerebral peduncle

The cerebral peduncle, by most classifications, is everything in the mesencephalon except the tectum.

The region includes: midbrain tegmentum crus cerebri substantia nigra pretectum.

The peduncles are also known as the crus cerebri. There are numerous nerve tracts from motor areas

of the brain project to the cerebral peduncle and then project to various thalamic nuclei.

TTegmentumegmentum

The tegmentum (from Latin for "covering") is the part of the midbrain extending from the substantia nigra to the cerebral aqueduct in a horizontal section of the midbrain and forms the floor of the midbrain which surrounds the cerebral aqueduct.

Structures that have developed to grow ventral or lateral outside this primitive tube as add-ons(e.g. the crus cerebri in the anterior of the midbrain) are not considered part of the 'tegmentum' as they were not part of the primitive neural tube but grew as projections from the cerebral cortex.

Parts that were inside the primitive neural tube and remained an integral part of it after complete development (e.g. the red nucleus) are considered part of the tegmentum.

Pertinent areas of Tegmentum ventral tegmental area Red Nucleus

VVentral tegmental areaentral tegmental area

Part of the midbrain, lying close to the substantia nigra and the red nucleus.

It is rich in dopamine and serotonin neurons, and is part of two major dopamine pathways:

the mesolimbic pathway, which connects the VTA to the nucleus accumbens

the mesocortical pathway, which connects the VTA to cortical areas in the frontal lobes.

Function - The ventral tegmentum is considered to be part of the pleasure system, or reward circuit, one of the major sources of incentive and behavioural motivation.

psychostimulant drugs (such as cocaine) directly target VTA. Hence, it is widely implicated in neurobiological theories of addiction.

It is also shown to process various types of emotion and security motivation, where it may also play a role in avoidance and fear-conditioning.

Red nucleusRed nucleus

The red nucleus (nucleus ruber) is a structure in the rostral midbrain involved in motor coordination.

The red nucleus mainly controls the muscles of the shoulder and upper arm, but it has some control over the lower arm and hand as well. It is less important in its motor functions for humans than in many other mammals, because, in humans, the corticospinal tract is dominant.

However the crawling of babies is controlled by the red nucleus, as is arm-swinging in normal walking.

The rubrospinal projection: The red nucleus receives many inputs from the contralateral cerebellum and an input from the ipsilateral motor cortex, and sends efferent axons to the contralateral half of the spinal cord.

Substantia nigra (1)Substantia nigra (1)

The substantia nigra, (Latin for "black substance") is a heterogeneous portion of the midbrain.

The substantia nigra is responsible for dopamine production in the brain, and therefore plays a vital role in reward and addiction.

It consists of two strongly contrasted ensembles: pars compacta - contains neurons which are coloured

black (black stripes) by the pigment neuromelanin that increases with age

pars reticulata – dendrites from pars compacta neurons

Substantia nigra (2)Substantia nigra (2)

Dopamine is biosynthesized in the dopaminergic neurons, primarily in the substantia nigra pars compacta.

Disruption in the biosynthesis or transmission of dopamine can lead to serious motor and cognitive deficits, such as occurs in Parkinson's disease.

The neurons of the pars reticulata are fast-spiking pacemakers, generating action potentials in the absence of synaptic input.

The pars reticulata is one of the two primary output nuclei of the basal ganglia system (next to Pallidum) to the motor thalamus.

The function of the neurons of the pars reticulata is profoundly changed in parkinsonism and epilepsy.

Basal ganglia (1)Basal ganglia (1)

The basal ganglia are important to life nuclei in the brain interconnected with the cerebral cortex, thalamus and brainstem.

Basal ganglia are associated with a variety of functions: motor control, cognition, emotions and learning.

Parts: the striatum (putamen, caudate nucleus, nucleus

accumbens) globus pallidus (internal and external segments) subthalamic nucleus (STN) substantia nigra (SN) - compacta (SNc), reticulata

(SNr)

Basal ganglia (2)Basal ganglia (2)

Basal ganglia (3)Basal ganglia (3)

Striatum Striatum

The striatum is a subcortical part of the telencephalon. It is a major part of the basal ganglia system: its input

station. Function:

planning and modulation of movement pathways involved in a variety of other cognitive processes involving

executive function is activated by stimuli associated with reward, but also by

aversive, novel, unexpected or intense stimuli Pathology:

Parkinson's disease results in loss of dopaminergic innervation to the striatum (and other basal ganglia)

The lesion of the striatum is also involved in the Huntington disease, choreas, choreoathetosis and dyskinesias.

Globus pallidus (pallidum)Globus pallidus (pallidum)

The globus pallidus is a subcortical structure of the brain.

It is a major element of the basal ganglia system.

Parts: Lateral pallidum (GPe): receives a strong

glutamatergic projection from the subthalamic nucleus. Sends GABAergic axons to other parts of basal ganglia.

Medial pallidum (GPi): receives a strong glutamatergic projection from other parts of Basal ganglia. Sends GABAergic axons to the thalamus.

Subthalamic nucleusSubthalamic nucleus

The subthalamic nucleus is a small lens-shaped nucleus in the brain.

It is a part of the basal ganglia system. The chronic stimulation of the nucleus leads to a

clear improvement of Parkinsonian symptoms. Unilateral destruction or disruption of the

subthalamic nucleus – which can commonly occur via a small vessel stroke in patients with diabetes, hypertension, or a history of smoking – produces hemiballismus (a movement disorder, characterised by unilateral wild, large amplitude flinging movements of the arm and leg, normally causing falls and preventing postural maintenance.)

Thalamus (1)Thalamus (1)

The thalamus (from Greek = bedroom, chamber) is a pair and symmetric part of the brain.

It constitutes the main part of the diencephalon.

Thalamus (2)Thalamus (2)

Thalamus (Thalamus (33))

dorsal thalamus, which is comprised of roughly 15 nuclei with relay cells that project to the cerebral cortex.

ventral thalamus (the major portion of which is the thalamic reticular nucleus) - reticular cells are GABAergic and project into the dorsal thalamus to inhibit relay cells.

Function: to gate and otherwise modulate the flow of

information to cortex. plays an important role in regulating states of sleep

and wakefulness. sensory systems auditory, somatic, visceral, gustatory

and visual systems "motor" systems

Dopamine (1)Dopamine (1)

dopamine works as a neurotransmitter in the CNS

dopamine receptor - D1, D2, D3, D4 and D5, and their variants

Dopamine is produced in several areas of the brain, including the substantia nigra.

Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary.

Dopamine (2)Dopamine (2)

Dopamine can be supplied as a medication that acts on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure.

Since dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the CNS.

To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease and Dopa-Responsive Dystonia, L-DOPA (levodopa), (the precursor), can be given because it can cross the blood-brain barrier.

Function of dopamineFunction of dopamine

Dopamine is central to the reward system. Dopamine neurons are activated when an unexpected reward is presented. In nature, we learn to repeat behaviors that lead to unexpected rewards. Dopamine is therefore believed by many to provide a teaching signal to parts of the brain responsible for acquiring new motor sequences, i.e., behaviors. Movement Cognition Regulating prolactin secretion Motivation and pleasure (food, sex, drugs)

Disruption to the dopamine system Parkinson’s disease, schizophrenia, psychosis, depression

SerotoninSerotonin

Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the CNS (also in GIT).

Function: regulation of anger, aggression, body temperature, mood, sleep, vomiting, sexuality, and appetite.

Disorders: increase in aggressive and angry behaviors, clinical depression, obsessive-compulsive disorder, migraine, irritable bowel syndrome, tinnitus, fibromyalgia, bipolar disorder, and anxiety disorders.

Extremely high levels of serotonin can have toxic and potentially fatal effects, causing a condition known as serotonin syndrome. In practice, such toxic levels are essentially impossible to reach through an overdose of a single anti-depressant drug.

Parkinson's disease (1)Parkinson's disease (1)

Parkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech.

It is characterized by: Change in facial expression (staring, lack of blinking) Failure to swing one arm when walking Flexion (stooped) posture "Frozen" painful shoulder Limping or dragging of one leg Numbness, tingling, achiness or discomfort of the neck

or limbs Softness of the voice Subjective sensation of internal trembling Resting

tremor

Parkinson's disease (Parkinson's disease (22))

Mnemonic device T - Tremor - Involuntary trembling of the

limbs (resting tremor) R - Rigidity - Stiffness of the muscles A - Akinesia - Lack of movement or

slowness in initiating and maintaining movement

P - Postural instability - Characteristic bending or flexion of the body, associated with difficulty in balance and disturbances in gait

Parkinson's disease (2)Parkinson's disease (2)

Dopaminergic pathways of the human brain in normal condition (left) and Parkinson's disease (right).

Red Arrows indicate suppression of the target, blue arrows indicate stimulation of target structure.

Huntington's diseaseHuntington's disease

most obvious symptoms are abnormal body movements called chorea and a lack of coordination.

but it also affects a number of mental abilities and some aspects of personality.

Chorea is characterized by brief, irregular contractions that are not repetitive or rhythmic, but appear to flow from one muscle to the next.

genetic disorder, symptoms commonly become noticeable in a person's 40’s.