Neuronal Circuits & Dopamine Flashcards
What is the main excitatory neurotransmitter in the brain?
Glutamate
What is the main inhibitory neurotransmitter in the brain?
GABA
What is the axon?
Main conducting unit of a neurone
What occurs at the pre-synaptic terminal?
Electrical signal converted to chemical signal via neurotransmitter release
What is the cortex?
Darkened region on the edge of the brain
Anything lower than subcortical
What is the resting potential of a neuron?
-70mV
What occurs at depolarisation of a neuron?
Influx of sodium into cells due to opening of sodium channels
What is the membrane potential after depolarisation?
+30mV
What occurs at repolarisation of a neuron?
Opening of potassium channels causing efflux
What occurs at hyperpolarisation of a neuron?
Brief reduction in membrane potential as potassium channels are slower to close
What is the role of the Sodium-Potassium ATPase in the neuron?
Works to return ions back to original position for re-activation
What is the role of ACh in neurotransmission?
Binds to both muscarinic and nicotinic receptors on post synaptic membranes
What is the clinical benefit of inhibition of acetyl cholinesterase?
Increases synaptic availability of ACh upon release which can be beneficial in dementia
Describe the action of Acetylcholinesterase.
Breaks down ACh to form Acetyl coA and choline
50% of choline is then taken up into presynaptic terminal by active transporter
Describe the action of choline acetyltransferase.
Forms ACh from acetyl coA and choline, present in neuronal terminal in excess
What are the 5 subunits of nicotinic receptors? How are they made up?
Alpha Beta Delta Epsilon Gamma Found in different combinations of types of nicotinic ACh receptors Found in both muscle and neurons
Describe the activation of a neuromuscular junction.
Release of ACh initiated via arrival of action potential in motor neuron
Depolarisation of nerve ending leads to opening of presynaptic calcium channels
Transmitter release via vesicle exocytosis
Postsynaptic ion channels open
Sodium ions influx into muscle cell causing depolarisation
Action potential generates on membrane of skeletal muscle cell
What is myasthenia gravis?
Immune system produces antibodies to block/damage muscle ACh receptors
Prevents muscle contraction
Causes lack of contraction and weakening
Which muscles are commonly affected in myasthenia gravis?
Eye and facial muscles
Those involved in swallowing
What treatments can be used in myasthenia gravis?
AChE inhibitors such as pyridostigmine tend to work best in mild cases
Can improve muscle contractions
How is dopamine formed?
L-Tyrosine (tyrosine hydroxylase)—> L-dopa (dopa decarboxylase)—-> dopamine
What is the rate determining step in dopamine formation?
Tyrosine hydroxylase
Normally saturated by substrate
What action do D1 dopamine subtypes have?
Excitatory
What action do D2 dopamine subtypes have?
Inhibitory
What are the two metabolic enzymes of dopamine?
Catechol-O-methyltransferase
Monoamine oxidase
What is the pleasure circuit?
Projections from the midbrain controlled by dopamine
Describe the reuptake of dopamine?
Catecholamines have highly specific active transport mechanisms to remove transmitter from the synapse into the presynaptic terminals Dopamine transporter (DAT)
What effect do drugs of abuse have on the pleasure circuit?
Prolong dopamine presence in the synapse
Can cause hallucinations due to blocking DAT
Little effect in frontal lobe as dopamine tends to be broken down via enzymes
Where is the nigrostriatal pathway?
Substantia nigra to striatum
What does the dorsal striatum control? Which pathway is it in?
Controls motor control
Nigrostriatal pathway
What does the associative striatum control? Which pathway is it in?
Learning Habituation Memory Attention Motivation Emotion Volition Nigrostriatal pathway
What are positive symptoms of schizophrenia associated with?
Increased dopamine in associated striatum
Where is the mesolimbic pathway?
Ventral tegmental area in midbrain to limbic regions
What does the mesolimbic pathway control?
Reward
Motivation
Affect
Memory
Which areas of the brain are involved in the mesolimbic pathway?
Ventral striatum (nucleus accumbens)
Amygdala
Hippocampus
Medial pre-frontal cortex
Which pathway is involved in cognitive deficits seen in schizophrenia?
Mesocortical pathway
Where is the mesocortical pathway?
Ventral tegmental to frontal cortex
Includes
What does the mesocortical pathway control?
Cognitive function
Motivation
Emotional response
Where is the tuberoinfundibular pathway?
Tuberal region to median eminence
Infundibular region at the top of the pituitary stalk
How does dopamine act in the tuberoinfundibular pathway?
Inhibits prolactin release from pituitary
Describe partial agonism in schizophrenia?
Recognition of the receptor, does not induce maximal activation
Too much dopamine balanced out without complete inhibition
Does not alter other dopamine pathways as severely as an antagonist. less side effects
i.e. aripiprazole
Describe the structure and function of ionotropic receptors?
Ligand gated ion channel opened by transmitter
Allows passage of excitatory sodium ions or inhibitory potassium/chloride ions
Involved in fast transmission
Give examples of neurotransmitters that are substrates for ionotropic receptors.
Acetylcholine
Glutamate
GABA
Describe the structure and function of metabotropic receptors?
Receptor protein is coupled to effector via G-protein
Cellular effect much slower than ionotropic
Give examples of neurotransmitters that are substrates for metabotropic receptors.
Dopamine
Describe the function of kinase-linked receptors?
Slower responses
Endogenous agonists include hormones and GF
Involved in growth and differentiation
Describe the function of intracellular receptors?
Very slow responses, long lasting
Affect DNA transcription processes
Give examples of CNS stimulants.
Cocaine
Amphetamines
Nicotine
