CNS Transmission Flashcards
What are the sensory inputs?
External stimuli - Sound - Sight - Smell - Touch - Taste Internal stimuli - Pressure - O2/CO2 - Temperature - pH
What is an action potential?
Electrical signal along nerve
What is a neurotransmitter?
Chemical signal at nerve ending
What is the role of Ca at the pre-synaptic terminal?
Influx of Ca
Synaptic vesicles release neurotransmitter into synapse
Receptors detect and bind neurotransmitter
What is the main pre-ganglionic autonomic neurotransmitter and receptor?
Acetylcholine
Nicotinic receptors
What is the main sympathetic neurotransmitter and receptor?
Noradrenaline
a- and b-adrenoceptors
What is the main parasympathetic neurotransmitter and receptor?
Acetylcholine
Muscarinic receptors
What is the main somatic neurotransmitter and receptor?
Acetylcholine
Nicotinic receptors
What are the requirements for chemical neurotransmission?
Synthesis/storage - Vesicular content Release - Na and K ion channels - Ca influx Inactivation - Uptake - Metabolism Receptors - Pre-junctional - Post-junctional
How is noradrenaline inactivated at the synapse?
Neuronal uptake - predominant removal
Extraneuronal uptake
Metabolism - very small contribution
What is the pre-junctional receptor for noradrenaline?
a2 receptor
Can drugs with peripheral actions also have effects on the CNS?
Yes, and dramatic ones, too
But only if they cross the BBB
Describe the uptake of noradrenaline at the synapse
Neuronal - High affinity - 90-95% Extraneuronal - Low affinity
What does cocaine do at the synapse?
Block neuronal uptake of NA
Increased response when nerves activated
Does cocaine have dose-response effects?
Yes South American Indians chewed leaf - Slow absorption - Low concentration - Relief from - Fatigue - Hunger - Altitude sickness - Pleasant subtle sense of well being - Psychological dependence Western society snorts, smokes, injects - Fast absorption - High concentration - Intense euphoria - Craving for more drug - Psychological and physical dependence - Psychotic symptoms, depression, anxiety, fatigue - Peripheral effects: hypertension, tachycardia, coronary vasospasm, dysrhythmia, convulsions
What does amphetamine do at the synapse?
Displace noradrenaline from storage vesicles
- NA released even during low activity
Competes for uptake receptors
What are the functions associated with noradrenaline?
Stimulant
Mood
Appetite
Cardiovascular
What are the catecholamines?
Noradrenaline
Dopamine
Adrenaline
What type of chemical is serotonin?
Amine
What are the amino acid neurotransmitters?
GABA
Glutamate
Glycine
Aspartate
What are the peptide neurotransmitters?
Opioids
NPY
CCK
What is a gaseous neurotransmitter?
Nitric oxide
Which neurotransmitter, unlike others, is made on demand?
Nitric oxid
What is the distribution of neurotransmitters?
Some widespread
Others highly localised
Describe catecholamine synthesis
EC: Tyrosine
IC: Tyrosine hydroxylase > L-DOPA > doa decarboxylase > dopamine
Vesicle: Dopamine-b-hydroxylase > NA > phenyl-ethanolamine-N-methyl transferase > adrenaline
In which cells is adrenaline synthesised?
Adrenal chromaffin cells
Which nerves synthesises dopamine only?
Dopaminergic nerves
Where are some areas of the brain to which noradrenergic pathways project?
Cerebellum
Caudal raphe nuclei
Thalamus
Where are some areas of the brain to which dopaminergic pathways project?
Striatum
Pre-frontal cortex
What are some of the pathways in which dopamine is involved?
Movement - Parkinson's: depletion of dopamine in basal ganglia Behaviour: - Schizophrenia: changes in dopamine rich areas like: - Frontal cortex - Basal ganglia - Temporal lobe Dependence: - Dopamine actions in nucleus accumbens and ventral tegmental area Pituitary function - Prolactin secretion Vomiting - Chemoreceptor trigger zone outside BBB - Less important
What neurotransmitter uptake does cocaine block?
Noradrenaline
Dopamine
Serotonin
What is cocaine’s dopaminergic action linked to?
Dependence
What type of channel does cocaine also block?
Na channels
Happens at much higher concentrations
Can a synapse be excitatory AND inhibitory?
No, can only be one or the other
Can a neurotransmitter be excitatory AND inhibitory?
Yes, depending on which receptor is present
What type of receptor is a nicotinic receptor?
Ligand-gated ion channel
Excitatory
Na influx driven depolarisation
What type of receptor is a GABA A receptor?
Ligand-gated ion channel
Inhibitory
Cl influx driven hyperpolarisation
What are post-synaptic receptors responsible for?
Action potential generation/modulation
What are pre-synpatic receptors responsible for?
Transmitter release
What are neurotrophic factors secreted by glial cells involved in?
Development
Survival
What is the role of glia in neurodegenerative diseases?
Loss of neuroprotective factors
Toxic insult
What complicates the rational approach to identifying transmitter levels in disease
More than one transmitter usually involved
One transmitter involved in many pathways
Secondary/adaptive responses
Effect of transmitter levels on
- Synthesis
- Receptor expression
- Transporter expression
