Cellular Physiology of the Brain - Neurotransmission Flashcards
What are the three chemical classes of neurotransmitters in the CNS?
Amino acids
Biogenic amines
Peptides
Examples of amino acid neurotransmitters in the CNS
Are they excitatory or inhibitory?
Glutamate - excitatory
GABA -inhibitory
Glycine - inhibitory
Examples of biogenic amines neurotransmitters in the CNS
- Acetylcholine
- Noradrenaline
- Dopamine
- Serotonin / 5-HT
- Histamine
Examples of peptides neurotransmitters in the CNS
- Dynorphin
- Encephanlins
- Somatostatin
- Cholecystokinin
- Neuropeptide Y
What is the main excitatory amino acid neurotransmitter?
Glutamate
What are the inhibitory amino acid neurotransmitters?
Glycine
GABA
Types of glutamate receptors
How do they exert their effects
Ionotropic: contain integral ion channel
- AMPA: permeable to Na + K
- Kainate: permeable to Na + K
- NMDA receptors: permeable to Na, K + Ca
.
Metabotropic: G protein coupled receptors
- mGluR1-7: via IP3/Ca or changes in cAMP
Types of ionotropic glutamate receptors
What are they permeable to?
- AMPA: permeable to Na + K
- Kainate: permeable to Na + K
- NMDA receptors: permeable to Na, K + Ca
What does glutamate release cause?
- depolarisation on post synaptic cell by acting on ligand gated ion channels
- excitatory postsynaptic potential
- causes APs
What do AMPA receptors mediate?
Initial fast depolarisation
What do NMDA need to allow ion flow?
Glutamate binding
Cell to be depolarised
What do NMDA receptors have an important role in?
How?
Learning + memory
- activation of NMDA receptors > up regulates AMPA receptors
- strong high frequency stimulation casues long term potentiation
- Ca2+ entry through NMDA receptors is important for LTP
What is long term potentiation?
Persistent strengthening of synapses leading to long lasting increase in signal transmission between neurones
What can cause exictotoxicity?
Too much Ca2+ entry through NMDA receptors
(Too much glutamate)
What is the main inhibitory transmitter in the brain?
GABA
What is the main inhibitory transmitter in the brainstem + spinal cord?
Glycine
How do inhibitory amino acid transmitter work?
- GABA + glycine have integral Cl- channels
- opening of the channels + Cl- influx causes hyperpolarisation
- inhibitory post synaptic potential
- decreased firing of AP
What drugs enhance the response to GABA?
What effects do they have?
Barbiturates
Benzodiazepines
Sedative + anxiolytic
What is benzodiazepines used to treat?
Anxiety
Insomnia
Epilepsy
What are barbiturates not used as much now?
Risk of fatal overdose
Addictive
What receptors do ACh act on in the brain?
Nicotinic
Muscarinic
What are cholinergic pathways in the CNS involved in?
Arousal
Learning
Memory
Motor control
Key dopaminergic pathways in CNS
What are their functions?
- nigrostriatal: motor control
- neocortical + mesolimbic: mood, arousal + reward
Degeneration of what pathway causes Parkinson’s disease?
Nigrostriatal
Overactivity of what pathway may contribute to schizophrenia?
Mesolimbic
Why can amphetamine use cause similar symptoms to schizophrenia?
- Causes release of dopamine
- Overactivity of dopamine can contribute to schizophrenia
What is the nigrostriatal pathway between?
What is its function?
What is its clinical significance?
- substantia nigra to striatum
- motor control
- degeneration causes Parkinson’s disease
What is the mesolimbic pathway between?
What is its function?
What is its clinical significance?
- midbrain to limbic system
- mood, arousal, reward
- Overactivity can contribute to schizophrenia
What is the neocortical pathway between?
What is its function?
- midbrain to cerebral cortex
- mood, arousal + reward
How can Parkinson’s disease be treated?
co-careldopa
- levodopa (dopamine precursor)
- converted to dopamine by DOPA decarboxylase
- given with carbidopa
Why do you give carbidopa with L-DOPA in treatment of Parkinson’s disease?
- you want levodopa to be converted to dopamine in the brain not the periphery
- high levels in periphery can effect heart, GI + urinary systems
- cardbidopa does not cross BBB + inhibits conversion in periphery
Outline noradrenergenic pathways in CNS
- cell bodies of NA containing neurone within brainstem locus coeruleus
- diffuse release throughout cortex, hypothalamus + cerebellum
- involved in behavioural arousal
Where does most noradrenaline come from?
Locus coeruleus in brainstem
What is a low level of NA related to?
Depression
When are locus coeruleus neurones inactive?
During sleep
Functions of serotonin
Sleep/wakefullness
Mood
What is used for the treatment of depression or anxiety?
Serotonin selective reuptake inhibitors SSRIs
Where is serotonin released from?
Raphe nuceli of brainstem
What transmitters are involved in pain transmission?
Dynorphin
Encephalins
