Cellular Physiology Of The Brain Flashcards
List 4 roles of Astrocytes
- Help to provide nutrition for neurones via Glucose-lactate shuttle
- Uptake of neurotransmitter to keep concentration low
- Maintain ionic environment via K+ buffering
- Help to form blood brain barrier
Can neurones store or produce glycogen?
No
How do astrocytes provide nutrition to neurones
- Produce lactate from blood glucose (which is 1st converted to Glycogen and Pyruate in the cell)
- Lactate transported to neuron via Glucose-lactate shuttle
- Lactate converted to Pyruvate in neurone and used to make ATP
Name a toxic neurotransmitter that can be taken up by astrocytes
Glutamate
List the features of K+ buffering by Astrocytes
- Astrocytes have a RMP even more (-ve) than that of neurones
- Na-K ATPase and NKCC2 channels involved
- Astrocytes are connected to each other, so ions can move between them
Compare Microglia in resting and activated phases
These cells can act as APCs
Resting: Dendritic with long projections
Activated/ Phagocytic: Compact with disappearance of dendrites
Describe 3 structural features of the Blood Brain Barrier
- Tight junctions between endothelial cells of capillaries
- Basement membrane around capillaries
- End feet of astrocyte processes surrounding capillaries
Describe the meaning of the CNS being immune privileged
- No inflammation tolerated due to rigidity of skull (would lead to damage/ compression of vessels -> neuron damage)
- Microglia act as Antigen Presenting Cells to T cells
- T cells enter CNS through Blood Brain barrier
List the 4 main sections of a neurone
- Cell soma
- Axon
Dendrites and Terminals, which often synapse with each other
Describe neurotransmitter release briefly
- Depolarisation causes opening of VGCCs
- Ca diffuses in and causes release of vesicles containing neurotransmitter
List the 3 chemical classes of neurotransmitters in the CNS
- Amino acids
- Biogenic amines
- Peptides (Encephalin, Dynorphin, Somatostatin, CCK, Neuropeptide Y)
Which chemical class do the following neurotransmitters belong to?
- Glutamate
- GABA
- Glycine
Are they inhibitory or excitatory?
All are amino acid neurotransmitters
Glutamate- Excitatory
GABA and Glycine- Inhibitory
List 5 Biogenic Amines
- ACh
- Dopamine
- NA
- Histamine
- Serotonin (5-HT)
Over 70% of CNS synapses involve the use of which neurotransmitter?
Glutamate (The major excitatory neurotransmitter)
Compare the 2 classes of Glutamate receptors
Ionotropic: Contain an integral ion channel that opens upon activation, leading to depolarisation
Metabotropic: a GPCR linked to either;
- Changes in IP3 and Ca mobilisation
OR
- Adenylyl Cyclase inhibition and reduced cAMP levels
Compare the 3 types of Ionotropic Glutamate receptors
AMPA Receptors: Permeable to Na and K ions
Kainate receptors: Permeable to Na and K ions
NMDA receptors: Permeable to Na, K and CA ions
Describe the role of the 2 types of Ionotropic Glutamate receptors present in Glutamatergic synapses
- AMPA receptros mediate the initial depolarization
- NMDA receptors are permeable to Ca
In order for Ca to flow through NMDA receptors what are 2 things required?
What chemical acts on these receptors as a co-agonist?
- Cell must be depolarised
- Glutamate must bind
Glycine
Glutamate receptors have a role in learning and memory.
What can NMDA receptor activation cause?
What does strong, high frequency stimulation cause?
Up-regulation of AMPA receptors
Long Term Potentiation, LTP (Ca entry through NMDA receptors is important for this)
What can excess Ca entry through NMDA receptors cause?
Excitotoxicity (too much glutamate) as Ca is toxic in high Intracellular concentrations
Name the main inhibitory neurotransmitters in the;
- Brain
- Brainstem
- Spinal Cord
Brain: GABA
Brainstem and Spinal Cord: Glycine
Describe briefly how binding to GABAa and Glycine receptors cause Hyper-polarisation leading to an IPSP
- Both receptors have integral Cl- channels
- These channels open and Cl- diffuses in
- Inside of neuron is now more negative-> reduced firing of APs
Compare GABAa and GABAb receptors
GABAa: Ligand gated receptors
GABAb: GPCRs, have a modulatory role
Name 2 types of drugs that act on GABAa receptors
How do they affect the receptors?
- Barbiturates
- Benzodiazepines
Enhance the response of the receptors to binding by GABA
DO NOT BIND TO THE RECEPTORS THEMSELVES
Describe the clinical use of Barbiturates
- Sedative and Anxiolytic effects
- Sometimes used as anti-epileptic drugs to decrease brain electrical activity)
(Not used due to risk of fatal overdose as well as dependence)
Describe the clinical use of Benzodiazepines
- Sedative and Anxiolytic effects
- Used to treat anxiety, insomnia and epilepsy
Is ACh mainly excitatory or inhibitory in the CNS?
Why are they often present on PRE-synaptic terminals?
Excitatory
To enhance the release of other neurotransmitters
List 4 Cholinergic pathways in the CNS
- From Striatum Nigra to Thalamus
- Local interneurons in Corpus Striatum (Striatal interneurons)
- From Basal forebrain + Brainstem to Hippocampus + Parts of the Cortex
What are 4 things that the Cholinergic CNS pathways are involved in?
- Arousal
- Learning
- Memory
- Motor Control (From SN to Thalamus)
Degeneration of cholinergic neurones in what nucleus is associated with Alzheimer’s?
What drugs can be used to alleviate symptoms of this disease?
Nucleus basalis
Cholinesterase inhibitors
List 3 Dopaminergic CNS pathways
What are they involved in?
- Nigrostriatal pathways (Between SN and Corpus Striatum), involved in in Motor control
- Mesolimbic and Mesocortical pathways, involved in Mood, Arousal and Reward
List 2 conditions associated with dopamine dysfunction
- Parkinson’s
- Schizophrenia
Describe the relationship between Parkinson’s and Dopamine
How can Parkinson’s be treated?
- Associated with loss of dopaminergic neurones in Striatal pathway (SN to Corpus Striatum)
- Levodopa/ L-DOPA, a precursor of Dopamine (Converted to Dopamine by AADC/ DOPA Decarboxylase)
Describe the relationship between Schizophrenia and Dopamine
Possibly due to excess Dopamine release
Why can Amphetamines cause Schizophrenic behaviour?
What kind of drugs can be used as antipsychotics?
Release Dopamine and Noradrenaline
Dopamine antagonists at D2 receptors
Describe the flow of L-DOPA through the Blood Brain Barrier
Freely crosses the BBB via an LNAA (Large Neutral AA transporter)
AADC is present in the brain AND in the periphery.
How do we prevent a rise in peripheral dopamine concentration when we treat with L-DOPA?
Give Carbidopa;
- Inhibits AADC
- Can not cross BBB
Therefore, AADC is only inhibited in the periphery and not in the brain
Outline the CNS Noradrenergic pathways
- Cell bodies of neurones containing NA in the Brainstem (Pons and Medulla)
- Widespread NA release throughout Cortex, HT, Amygdala, Cerebellum
Where does most NA in the brain come from?
When are they inactive, when does activity increase?
- Neurones in the Locus Coeruleus
- Inactive during sleep, Activity increases during behavioural arousal
(Amphetamines increase release of NA and Dopamine, as well as wakefulness)
What substance deficiency may depression be associated with?
Noradrenaline
List 2 functions of the Serotonin pathways in the CNS
- Mood
- Sleep/ wakefulness
How do SSRIs help in the treatment of depression and anxiety disorders?
(Selective Serotonin Re-uptake Inhibitors)
Inhibit serotonin uptake, so increased concentration of Serotonin present
Which Glutamatic receptors are involved in Fast and Slow excitations
Fast- Ionotropic
Slow- Metabotropic
Which neurotransmitter is produced by the Raphe Nuclei
Serotonin (5-HT)
Where are Noradrenaline and Dopamine made?
NA- Locus Coeruleus
Dopamine- Substantia Nigra
