Parkinson’s Disease - structure & physiology outline David Bozarth - Biology 318 - Fall 2003

nerve cell

• cell body
• axon
• synapse
• neurotransmitter

brain

• cerebrum : sensation, movement, thinking
• cerebellum : coordination of fine movement
• midbrain : low-level body functions (sleep, breathe, etc.)
• spinal cord : transmission line for nerve impulses

thalamus

• center of brain

• relay station for all sensory pathways from the cerebral cortex

• involved also in transmission of impulses among the cerebellum, limbic system, and basal ganglia

basal ganglia

• ganglion means "knot" of cells

• grey matter inside white matter deep in center of brain

• fiber pathways tend to run from the sensory and motor cortex, down through B.G., back up to motor centers

• "side track" off the relay station of the thalamus

• associative area, constantly involved in processing of information by the cortex

• complex relationships and influences on movement within the basal ganglia, interaction with thalamus

subthalamic structures

• located in midbrain, below thalamus

• work together to control tremors

• red nucleus, substantia nigra

Substantia nigra

• "the black substance"

• nerve cells that make:

• dopamine and norepinephrine (neurotransmitters that mediate tremor control

• neuromelanin (pigment that gives these cells their dark color)

• Substantia nigra cells can be destroyed by the chemical MPTP, which can be a by-product of incorrect synthesis of heroin

• communicates with other brain structures via the striatum

striatum

• bundle of fibers running among the basal ganglia and to the thalamus (The Brain p.328)

• Substantia nigra connects to the striatum

• this nigrostriatal pathway uses dopamine for signaling

• Substantia nigra receives impulses from cortex via other basal ganglia (caudate & putamen)

• Substantia nigra sends impulses to other basal ganglia (caudate & putamen), also to the cortex via thalamus

• Striatal neurons exert inhibitory effect on movement via the “direct pathway” through the thalamus to cortex

• In this “direct pathway” Substantia nigra exerts an excitatory effect on striatal neurons

Ø net result = Substantia nigra inhibits movement signals flowing through the striatum

Ø in this mode, damage to Substantia nigra is thought to result in tremors (inadequate control of movement)

• there is also an “indirect pathway” by which the Substantia nigra facilitates movement

Ø in this mode, damage to the Substantia nigra is thought to result in slow, difficult movement in Parkinson’s

neuromelanin

• stacked planar layers of carbon rings (like dry carbon)

• dopamine is probably involved in biosynthesis of neuromelanin

• tissue studies

• normal aging shows INCREASE of neuromelanin in substantia nigra

• associated with lipofuscin - recall aging & lipofuscin granules

• stiffness in cell membranes and muscle fibers with aging

• associated with aging CNS tissues & senile dementia

• Parkinson's shows DECREASE of neuromelanin due to death of pigmented cells of S.N.

• neuromelanin has chelating ability - affinity for iron, lipids, toxins, psychoactive chemicals

• a protective role in brain has been suggested

dopamine

• neurotransmitter released into synapse between neurons, and binds to receptors on the target neuron

• underproduction of dopamine à understimulation of the target (as occurs in Parkinson’s)

• overproduction of dopamine à overstimulation of the target (occurs with amphetamine use)

• an enzyme present in the synapse facilitates re-uptake and recycling of used dopamine by source
• blockage of this enzyme à continuing stimulation of the target (occurs with cocaine use)

• Substantia nigra neurons convert the amino acid tyrosine into L-dopa, then L-dopa into dopamine

• deficiency of dopamine can not be relieved by administering dopamine directly (can’t cross blood/brain barrier)
• treatment: L-dopa can cross barrier, and cells of Substantia nigra can convert it to dopamine

• other interesting facts about dopamine:

• a number of theories and studies have suggested imbalance of dopamine activity in:
• schizophrenia
• depression
• alcoholism

• 1997 study at U. Arizona, on administration of THC and a related cannabinoid:
• shown to increase dopamine activity in the substantia nigra and another brain area
• suggested this may provide a mechanism for different blends of cannabinoids to reinforce the
• overall psychoactive effect

• 1998 study in Switzerland suggested that:
• ”midbrain dopamine systems are involved in processing reward information and learning approach behavior”
• “Dopamine neurons are activated by rewarding events that are better than predicted …and are depressed by events that are worse than predicted. By signaling rewards according to a prediction error, dopamine responses have the formal characteristics of a teaching signal postulated by reinforcement learning theories.”

• release of dopamine in part of basal ganglia (nucleus accumbens) increased sex drive in rats