b asal g anglia kelsey dumond, alex esposito, krista kaspar brianna malone, agata orlinski
TRANSCRIPT
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.