B ASAL G ANGLIA Kelsey Dumond, Alex Esposito, Krista Kaspar Brianna Malone, Agata Orlinski.

BASAL GANGLIAKelsey Dumond, Alex Esposito, Krista Kaspar Brianna Malone, Agata Orlinski

WHAT IS THE BASAL GANGLIA?

Group of nuclei that act in unison Form a fundamental component of the

forebrain, near the thalamus Left and right sides, mirror images of one

another 4 distinct structures

Striatum Pallidum Substantia Nigra Subthalamic Nucleus

STRUCTURE OF BASAL GANGLIA

Largest component – contains the Caudate Nucleus and the Putamen Two masses of gray matter

separated by large tract white matter (internal capsule)

Various brain areas input Striatum

Striatum output ONLY other areas of the BG

Connected to specific parts of Cerebral Cortex

96% Medium Spiny Neurons – GABAergic cells (inhibit targets)

Striatum

STRUCTURE OF BASAL GANGLIA

Globus Pallidus Striatum Globus Pallidus Globus Pallidus inhibitory

output motor-areas At absence of input, fire at

steady, high rates Signals from Striatum cause

them to pause or reduce rate of firing

Internal (GPi) and External (GPe) GPi receives signals from

striatum via direct and indirect pathways

GPe receives input mostly from striatum to subthalamic neurons

STRUCTURE OF BASAL GANGLIA

Source of Striatal input of

Dopamine

SNr (reticulata)

Usually works with GPi –

inhibits thalamus

SNc (compacta)

Produces Dopamine, maintains

balance in Striatal pathway

Substantia Nigra

STRUCTURE OF BASAL GANGLIA

Subthalamic Nucleus

Recieves input mainly from

Striatum and Cerebral Cortex

Projects output to Globus Pallidus

Only portion that produces

excitatory neurotransmitter

Glutamate

Stimulates SNr-GPi complex

Part of the indirect pathway

DIRECT PATHWAYCerebral Cortex [Primary Motor Cortex]Stimulates the StriatumInhibits the SNr-GPi complex (Substantia Nigra reticulata-Globus Pallidus interna complex)Inhibits the ThalamusStimulates the CortexStimulates Muscles/motor movement

Results in a Hyperkinetic State

INDIRECT PATHWAY

Cerebral Cortex [Primary Motor Cortex]Stimulates the StriatumInhibits the GPe (Globus Pallidus externa)Inhibits the Subthalamic NucleusStimulates the SNr-GPi complex (Substantia

Nigra reticulata-Globus Pallidus interna)Inhibits ThalamusStimulates CortexStimulates Muscles/motor movement

Results in a Hypokinetic State

ROLE OF DOPAMINE IN BASAL GANGLIA

In order to function at peak efficiency, need a certain amount of dopamine, via dopamine receptors: D1-5.

Reduces influence of Indirect Pathway Increases actions of Direct Pathway in Basal

Ganglia Excess of Dopamine:

Brain causes the body to make unnecessary movements

Deficiency of Dopamine: Movements may be delayed and/or

uncoordinated

FUNCTION OF BASAL GANGLIA

Voluntary Motor Control Action Selection: decision of which of several

possible behaviors to execute at a given time Procedural learning to routine behaviors and

habits Grinding teeth Cognitive, emotional functions Eye movements

Midbrain area (superior colliculus)

Example: Pick up a cup and bring up to lips – may involve

biceps or shoulder muscles. Basal Ganglia inhibits other muscles around those that may want to fire in order to focus on that one functionality – lateral inhibition

HUNTINGTON’S DISEASE An inherited disease that causes certain

nerve cells in the brain to waste away, especially in the basal ganglia

People are born with the defective gene, but the symptoms don’t appear until middle age

Some of the symptoms include: poor memory, depressing and/or mood swings, lack of coordination, twitching or other uncontrolled jerky movements, difficulty walking, speaking, swallowing

There is no known cure for the disease

VIDEO CLIP OF HUNTINGTON’S DISEASE

http://www.youtube.com/watch?v=kINXIjs_V3M&list=UUkEXB4TR4X2bERcpPy7X1pg&feature=player_detailpage

HOW IT EFFECTS THE BASAL GANGLIA

Huntington’s disease is caused by a mutation in a gene on chromosome 4. The job of it’s protein product ‘huntingtin’ is to direct the delivery of small packages (vesicles containing important molecules) to the outside of the cell

The coding normally contains the DNA sequence “CAG” repeated. For those without Huntington’s the number of times this triplet is repeated is around 10 to 26 times, but for those with the disease its repeated up to 40 times or more

HUNTINGTIN Also called HTT or HD (Huntington disease)

gene, is a gene which codes for a protein called the huntingtin protein

The gene and its product are under heavy investigation as part of Huntington’s disease clinical research

The gene can lead to numbers of glutamine residues present in the protein

In individuals affected by Huntington’s disease, it contains greater than 36 glutamine residues

BASAL GANGLIA & PARKINSON’S DISEASE

The basal ganglia plays a major role in many neurological conditions, dealing with movement disorders.

The basal ganglia is stimulated by the dopamingeric system Parkinson disease involves the loss or degeneration of

dopamine- producing cells (also known as cell death) in the substantia nigra. The reason for cell death is still unknown.

It progresses to other parts of the basal ganglia and to the nerves that control the muscles, involving other neurotransmitters.

The direct pathway is less able to function (so no movement is initiated) and the indirect pathway is in overdrive (causing too much inhibition of movement).

http://www.youtube.com/watch?v=XFcmuRgOWQU - Time 1 – 1:00

HEALTHY PATHWAY VS. PARKINSON’S PATHWAY

SYMPTOMS

CAUSE AND TREATMENTCommon in elders, after age 50

Possible causes: Environmental factors such as toxins Head trauma Genetics – how defective genes can play a role

Treatments: Drugs – to alleviate the symptoms Drugs - replace or mimic the lost dopamine and other

neurotransmitters Levodopa can make dopamine and replenish the brain's dwindling

supply.  Deep brain stimulation (DBS) can reduce tremors, slowness of

movements, and gait problems.

DBS THERAPY

http://www.youtube.com/watch?v=dHcQyj9jdec&playnext=1&list=PL9AF3AF853E3BE43B

BASAL GANGLIA & OTHER DISORDERS

Tourette Syndrome Onset in childhood Physical and vocal tics. Precise mechanism affecting inherited vulnerability-

currently unknown.

Hemiballismus decrease in activity of the subthalamic nucleus of

the basal ganglia. Damage to the caudate nucleus and subthalamic

nucleus. Some of the causes of this disorder are stroke,

traumatic brain injury, Nonketotic Hyperglycemia, Complications from HIV infection.

ARTICLE 1: TREATMENT OF MOTOR AND NON-MOTOR FEATURES OF PARKINSON'S DISEASE WITH DEEP BRAIN STIMULATION

Effects of DBS treatment

motor and non-motor features of Parkinson's disease.

stimulation of the subthalamic nucleus and globus pallidus improve motor features

non-motor symptoms improve after DBS, partially because of reduction of drug treatment, and partly as a direct effect of stimulation.

REFERENCES: http://en.wikipedia.org/wiki/Basal_ganglia

http://www.news-medical.net/health/Dopamine-Functions.aspxhttp://en.wikipedia.org/wiki/Huntington's_diseasehttp://www.hdsa.org/http://folding.stanford.edu/English/FAQ-Diseaseshttp://www.nist.gov/mml/bmd/srm-041211.cfmhttp://en.wikipedia.org/wiki/Kinesia_paradoxahttp://www.holistic-online.com/Remedies/parkinson/pd_brain.htmhttp://www.google.com/search?q=parkinson+disease+pathway&client=safari&rls=en&source=lnms&tbm=isch&sa=X&ei=ZQ9sUYqfGK670QHH34FY&ved=0CAoQ_AUoAQ&biw=1184&bih=598http://www.google.com/search?q=parkinson+disease+pathway&client=safari&rls=en&source=lnms&tbm=isch&sa=X&ei=ZQ9sUYqfGK670QHH34FY&ved=0CAoQ_AUoAQ&biw=1184&bih=598

Treatment of motor and non-motor features of Parkinson's disease with deep brainFasano, Alfonso; Daniele, Antonio; Albanese, Alberto. The Lancet Neurology11. 5 (May 2012): 429-42.