Lecture 12 Flashcards
How does diffusion enable modulation systems of the brain?
Have effects over large areas of the brain
Many of the body’s sensory, motor and cognitive functions are carried out by fast, specific, spatially organized neural connections
Perform regulatory functions rather than specific tasks
e.g. Falling asleep/waking up/becoming attentive
Changing mood
Other functions involve more general alterations in the function of the brain
What are common features of neurotransmitters?
Core of each system has a small set of neurons
Neurons arise from the central core of the brain
(often in the brain stem)
Each neuron may contact more than 100 000 postsynaptic neurons spread widely across the brain
Neurons release neurotransmitters into the extracellular fluid to allow diffusion to many neurons
Where are ACh located?
ANS
What are examples of catecholamines?
dopamine, noradrenaline
What is a good marker for cholinergic neurons and why?
ChAT; every neuron that releases ACh must have ChAT
How is Acetyl CoA produced by and where?
Cellular respiration, mitochondria
What does ACh degrade into and what enzyme catalyses the reaction?
Acetic acid and choline
AChE
What happens to the choline?
Taken up from the extracellular solution then recycled
What prevents release of ACh?
Botulinum toxin
- produced by bacteria in Black Widow Spider
- venom (latrotoxin) first increases ACh release at the neuromuscular junction then eliminates it
- seems to work by allowing a big Ca influx
What act as AChE inhibitors?
nerve gas insecticide Alzheimer's treatments - organophosphates - Alzheimer's disease shows reduced ACh
What block ACh receptors?
Nicotinic
curare
- neuromuscular blocks in blowpipes prevent prey from moving
alpha-Bungarotoxin
- from snake venom
- binds to nAChRs and takes days to unbind
- (Bungarus multicinctus)
Muscarinic atropine - found in Belladonna - causes pupils to dilate - women in the past used atropine to make eyes look bigger - can be fatal
What are the two cholinergic complexes of ACh?
Basal forebrain complex Pontomesencephalotegmental complex (brain stem)
What forms the Basal forebrain complex?
Medial septal nuclei
Basal nucleus of Meynert
How are the neurons distributed in the basal forebrain complex?
Neurons are scattered among several nuclei so the function of these nuclei are largely unknown
(Among the first to die in Alzheimer’s disease)
What does the Basal forebrain complex do?
Regulate brain excitability during arousal and sleep/wake cycles
What possible role does the Basal forebrain complex have?
Learning and memory
Where is the pontomesencephalotegmental complex located?
Pons and midbrain tegmentation
What is the precursor used in the synthesis of catecholamines?
tyrosine (an amino acid)
Where is tyrosine hydroxylase located?
All catecholaminergic neurons
rate limiting factor
Where is dopamine beta-hydroxylase located?
Synaptic vesicles
Where is PNMT located?
Bound in cytosol of presynaptic terminal
How are catecholamines removed and/or degraded?
Majority undergoes reuptake into presynaptic terminals Metabolized by: - catechol-O-methyltransferase (COMT) (mainly in cytoplasm) - Monoamine oxidase (MAO) (on outer mitochondrial membrane) - MAO-A: breaks down noradrenaline and serotonin - MAO-B: breaks down dopamine
What are the two catecholamine systems?
Dopaminergic and noradrenergic
What is the nigrostriatal pathway?
Neurons found in the substantia nigra of the midbrain
Axons project to the striatum
Pathway facilitates the initiation of voluntary movements
Degeneration of this pathway leads to Parkinson’s disease
- characterized by motor dysfunction
e.g. tremor, rigidity, lack of coordination, not very smooth muscle
