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

W HAT IS THE B ASAL G ANGLIA ? 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 B ASAL G ANGLIA 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 B ASAL G ANGLIA 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 B ASAL G ANGLIA 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 B ASAL G ANGLIA 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

D IRECT P ATHWAY Cerebral Cortex [Primary Motor Cortex] Stimulates the Striatum Inhibits the SNr-GPi complex (Substantia Nigra reticulata-Globus Pallidus interna complex) Inhibits the Thalamus Stimulates the Cortex Stimulates Muscles/motor movement Results in a Hyperkinetic State

I NDIRECT P ATHWAY Cerebral Cortex [Primary Motor Cortex] Stimulates the Striatum Inhibits the GPe (Globus Pallidus externa) Inhibits the Subthalamic Nucleus Stimulates the SNr-GPi complex (Substantia Nigra reticulata-Globus Pallidus interna) Inhibits Thalamus Stimulates Cortex Stimulates Muscles/motor movement Results in a Hypokinetic State

R OLE OF D OPAMINE IN B ASAL G ANGLIA 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

F UNCTION OF B ASAL G ANGLIA 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

H UNTINGTON S D ISEASE 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 dont 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

V IDEO CLIP OF H UNTINGTON S DISEASE &list=UUkEXB4TR4X2bERcpPy7X1pg&feature= player_detailpage

H OW IT EFFECTS THE BASAL GANGLIA Huntingtons disease is caused by a mutation in a gene on chromosome 4. The job of its 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 Huntingtons 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

H UNTINGTIN 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 Huntingtons disease clinical research The gene can lead to numbers of glutamine residues present in the protein In individuals affected by Huntingtons disease, it contains greater than 36 glutamine residues

B ASAL G ANGLIA & P ARKINSON S D ISEASE 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). - Time 1 – 1:00

H EALTHY P ATHWAY V S. P ARKINSON S P ATHWAY

S YMPTOMS

C AUSE AND T REATMENT Common 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 playnext=1&list=PL9AF3AF853E3BE43B playnext=1&list=PL9AF3AF853E3BE43B

B ASAL G ANGLIA & OTHER D ISORDERS 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.

A RTICLE 1: T REATMENT OF MOTOR AND NON - MOTOR FEATURES OF P ARKINSON ' 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.

R EFERENCES : Functions.aspxhttp://en.wikipedia.org/wiki/Huntington's_diseasehttp:// stanford.edu/English/FAQ-Diseaseshttp:// cfmhttp://en.wikipedia.org/wiki/Kinesia_paradoxahttp:// online.com/Remedies/parkinson/pd_brain.htmhttp:// pathway&client=safari&rls=en&source=lnms&tbm=isch&sa=X&ei=ZQ9sUYqfGK670QHH34FY&v ed=0CAoQ_AUoAQ&biw=1184&bih=598http:// way&client=safari&rls=en&source=lnms&tbm=isch&sa=X&ei=ZQ9sUYqfGK670QHH34FY&ved=0 CAoQ_AUoAQ&biw=1184&bih=598 Functions.aspxhttp://en.wikipedia.org/wiki/Huntington's_diseasehttp:// stanford.edu/English/FAQ-Diseaseshttp:// cfmhttp://en.wikipedia.org/wiki/Kinesia_paradoxahttp:// online.com/Remedies/parkinson/pd_brain.htmhttp:// pathway&client=safari&rls=en&source=lnms&tbm=isch&sa=X&ei=ZQ9sUYqfGK670QHH34FY&v ed=0CAoQ_AUoAQ&biw=1184&bih=598http:// way&client=safari&rls=en&source=lnms&tbm=isch&sa=X&ei=ZQ9sUYqfGK670QHH34FY&ved=0 CAoQ_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): 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):