WEEK 1:BASIC PRINCIPLES OF CNS AND BIOCHEMISTRY Flashcards
State the two types of synapses
chemical and electrical
Differentiate between the chemical and electrical impulse
1.Chemical impulse involves the neurotransmitter
2. can have an inhibitory or excitatory effect depending on the post synaptic receptor
3. Impulse move in one direction, from presynaptic to post synaptic
4. Cells not directly connected, there is a synaptic cleft
- Involves the movement of nerve impulse
2.Execute excitatory effect
3.biderectional
4.cell directly in contact with each other by connexons which form gap junctions - Very rare , found in cells which require fastest response, eye, some areas of brain and one pair of PNS
Describe the cycle of neurotransmitter
- Starts with production of Neurotransmitter in presynaptic neuron, then stored in secretory vacuoles.
- Propagation of action potential along axons result in the release of neurotransmitter into the synaptic cleft via exocytosis when calcium ion channels are open and there is influx if calcium ions into the synaptic cleft.
3.Stimulation of action potential on the post synaptic cell membrane by opening ion channels DIRECTLY or INDIRECTLY when the neurotransmitter binds to the receptor channels.
4.Removal of neurotransmitter from the synapse by destruction using enzymes or Reuptake into the pre-synaptic cell so the signal can work again
Why is there a need to remove the neurotransmitter from the synapse after use?
To avoid overstimulation of the postsynaptic cell, muscles and exocrine glands
Outline the cycle of acetylcholine neurotransmitter.
- Produced in cell body of presynaptic neuron then packaged and travels via axon to be stored in synaptic button (synaptic knob)
- ACh is released from into synaptic cleft
3.Binds to NICOTINIC RECEPTORS and activate G-protein to activate second messengers
4.MUSCARINIC RECEPTORS open ion channels
5.Removed by acetylcholinesterase
Outline the cycle of acetylcholine neurotransmitter.
- Produced in cell body of presynaptic neuron then packaged and travels via axon to be stored in synaptic button (synaptic knob)
- ACh is released from into synaptic cleft
3.Binds to NICOTINIC RECEPTORS and activate G-protein to activate second messengers
4.MUSCARINIC RECEPTORS open ion channels
5.Removed by acetylcholinesterase
2.
Outline the cycle of acetylcholine neurotransmitter.
- Produced in cell body of presynaptic neuron then packaged and travels via axon to be stored in synaptic button (synaptic knob)
- ACh is released from into synaptic cleft
3.Binds to NICOTINIC RECEPTORS and activate G-protein to activate second messengers
4.MUSCARINIC RECEPTORS open ion channels
5.Removed by acetylcholinesterase
Why does acetylcholine act differently in different neurons?
Because it has 2 different receptors and the way in which it works depends on the present receptor
Describe the MOA of the directly acting receptor of acetylcholine.
It is a sodium ion channel protein
Binding of acetylcholine opens the channels
Acetylcholine nitocinic receptor
Describe the MOA of indirect acetylcholine receptors
- Acetylcholine binds to a trimetric G-protein ,which will activate a membrane bound enzyme.
- Phospholipase C will cleave the membrane phospholipid, phosphatidyl Inositol-4,5- biphosphate (PIP2) into 1,2-diacylglycerol and inositol triphosphate
- 1,2-diacylglycerol cause opening of transmembrane ion channels
NOTE: The indirect opening of ion channels is slower than direct opening of, but it is possible for the same signal to cause other changes in the neuron.It is much commoner than direct opening.
Between Muscarinic and Nicotinic receptors, Which one is an indirect acting receptor?
Muscarinic receptor
Which cholinergic receptors are transmembrane ion channels?
Acetylcholine Nicotinic Receptors
Which cholinergic receptors are found in nerve endings which produce a fast respond?
acetylcholine nicotinic receptors
Name 3 excitatory receptors which are ligand gated ion channels and their transmitting neurons and neurotransmitter
- acetylcholine muscarinic receptor, Na/k
2.NMDA and Non NMDA receptors, Na/k, Glutamate
3.5HT3 receptor, Na/k, Serotonin
Name 2 inhibitory receptors which are ligand gated ion channels
Glycine, Cl
A class receptor, Gamma amino butyric acid, Cl
What are receptors which activate G protein called?
Intrinsic transmembrane proteins
Describe the mechanism of receptors which activate a titrimetric G-protein
- Binding of neurotransmitter activates a G protein
2.The activated G protein activates an effector enzyme ( intrinsic transmembrane protein)
- Effector enzyme will activate another intrinsic transmembrane protein
- The enzyme will synthesize an intracellular messenger , (the second messenger) which will carry message into the cell
5.The second messenger is produced form a substrate which is readily available in the cell
Nme the type of G proteins, their effector enzymes and second messengers
- Gs: Adenylate cyclase, cAMP
2.Gi: Phospholipase C, 1,2-diacylglycerol and inositol triphosphate
- Gt: cGMP phosphodiesterase , cGMP
4.Golf (smell+ taste), Adenylate cyclase, cAMP
5.Gk Potassium channel protein, k
- transducin
7.Light detection in the eye
Outline the main points to know on excitatory and inhibitory neurotransmitter response
- Sodium ion influx results in depolarization of membrane hence excitatory
- Cl ion efflux results in hyperpolarization hence inhobotory response
- Some neurotransmitters are both excitatory and inhibitory depending on which receptor they bind to
4.In some cases a single neuron may be contacted by many synaptic buttons and respond to several neurotransmitters, the net influx or efflux of ions will determine if the result is excitatory or inhibitory response
State 4 neurotransmitters which are amino acids
GABA, Glutamate, Aspartate, Gamma butyric acid and glycine
Outline neurotransmitters which are peptides
Opiods: enkephalins and endorphins
Substance P
Neuropeptide Y
What are the 2 subclasses of neurotransmitters which are biogenic amines
- ACh
- Monoamines
List all neurotransmitters which are monoamines
1.serotonin
2.Catecholamines: epinephrine, norepinephrine, dopamine
3.Histamine, agmatine
Name neurotransmitters which are purines and gases
Purines: ATP, GTP, Adenosine
Gases: NO,CO
List all types of neurotransmitters
- amino acid
- peptides
3.biogenic amines ( Acetylcholine + Monoamines)
4.purines
5.Gases
6.lipids
State the functions of serotonin
modulator of mood
is often associated with feelings of happiness, and plays a role in sleep quality, memory, and sexual desire
Name pathologies that as a result of high and low serotonin
high: such as in LSD drugs enhance serotonin effects, they are powerful hallucinary agents
Result in serotonin syndrome
Confusion
Increased reflexes
Restlessness
Hallucinations
Extreme agitation
Fluctuations in blood pressure
Increased heart rate
Nausea, vomiting, and diarrhea
Fever
Seizures
Coma
low : anxiety and depression
irritability, and mood swings
What are the function of dopamine?
Motor control
What are the effects of high and low dopamine?
high: schizophrenia
low: Parkinsons disease
Name the disease which is caused by GABA and acetylcholine destruction
huntingdons disease
Patients have difficulty in controlling movement and gradual decline in intellectual thinking and ability
How are neurotransmitters used pharmacologically?
They inhibit neurotransmitter or mimick its action
State examples of pharmacological use of neurotransmitters
1.Serotonin uptake inhibitors; Prozac
2. Acetylcholinesterase inhibitor: use in Myasthenia gravis (neostigmine)
3.L-DOPA :Parkinsons disease
4.opiaods (Morphine): use for analgesia
What amino acid is NO sythesized from?
Arginine
What are the functions of NO as a neurotransmitter?
control BP
involved in short term memory
NOTE: CO acts as NO as a neurotransmitter
CO and NO do not bind on the membrane, but they just pass through the membrane and bind to cytoplasmic receptors
NO acts as a messenger from the presynaptic cells, signalling presynaptic cells to increase neurotransmitter synthesis , thus increasing the signal intensity of that pathway
How does NO and CO work?
They diffuse through membrane and bind to cytoplasmic receptors
they result in increase of neurotransmitter synthesis in pre-synaptic neurons
What is learning?
It is the acquisition of knowledge and skills form experience and instruction or both
What is memory?
It is storage of acquired knowledge for later recall
What is memory trace?
It is the neuronal change responsible for retention of knowledge
Concepts are stored
What is short term memory?
lasts for seconds to hours
What is long term memory?
Lasts for days to years
What is consolidation?
It the transfer of short term memory into long term memory
What is working memory?
It is the one temporarily readily available for curent task at hand
State the differences between short and long term memory
S:* immediately stored after acquisition
*lasts for seconds to hours
*limited storage capacity
*Permanently forgotten quickly unless consolidated into long term memory
*Mechanism of storage involves transient modification in functions of preexisting synapses such as altering amount of neurotransmitter released
*Temporarily increases the responsiveness of the post synaptic cell to the neurotransmitter within the affected neuronal pathway
LONG TERM MEMORY
*Stored later after consolidation
*Lasts for days to years
*Large storage capacity
*Slower retrieval, except for thoroughly ingrained memories which are rapidly retrieved
*Storage involves permanent functional or structural changes between existing neurons, such as formation of new synapses, synthesis of proteins that play a key role
* It increases receptor numbers post synaptically
What is amnesia?
lack of memory
What is the difference between retrogade and anterogade amnesia?
RETROGADE
Retrograde amnesia is the inability to recall past memories. These patients are unable to retrieve information that was acquired before the onset of the amnesia condition.
usually can be due to Stroke, traumatic head injury, knocked unconscious
ANTEROGADE
*inability to consolidate memory into long term memory for future recall
*Patient can remember everything that happened before amnesia but cannot make new permanent long-term memory
It is associated with lesions in the TEMPORAL LOBE
Anterograde amnesia is the inability to create new memories while retrograde amnesia is the inability to recall past memories. So, this is the key difference between anterograde and retrograde amnesia. Anterograde amnesia patients can remember past memories while retrograde amnesia patients can form new memories. Anterograde amnesia is difficult to treat with pharmacological methods due to neuronal loss while retrograde amnesia can be treated by exposing the patient to past memories.
What is habituation?
decreased responsiveness to a repetitive representation of an indifferent stimulus.
Describe MOA of habituation
At a synapse, there is less calcium ion influx hence less neurotransmitter release resulting in less or absence of behavioral response controlled by the post synaptic efferent neuron.
In this case, the aplysia will not move its siphon it is touched
Describe MOA of habituation
At a synapse, there is less calcium ion influx hence less neurotransmitter release resulting in less or absence of behavioral response controlled by the post synaptic efferent neuron.
In this case, the aplysia will not move its siphon it is touched, it learns to ignore the stimulus
What is sensitization?
Increased responsiveness to a mild stimulus following a strong or noxious stimulus
Describe MOA of sensitization
A strong / noxious stimulus results in the release of SEROTONIN FROM FACILLITATING INTERNEURON. There is an increase in cAMP in presynaptic neuron. There is blockage of K ion channel. This results in a prolonged depolarization of action potential in PreSN. Calcium ion channels in presynaptic neuron are kept open for a longer time. There is increased calcium ion influx which results in increased neurotransmitter output in PreSN. This results in increased postsynaptic potential in efferent neuron. There is enhanced behavioral response to mild stimuli.
Describe MOA of sensitization
There is enhanced calcium ion influx hence more neurotransmitter release resulting in large post synaptic cell potential, there will be a vigorous reflex response.
In this case, the aplysia will be banged harder on the siphon and a vigorous withdrawal of the gill will be seen even when there is mild touch.
What is long term potentiation ?
It is the strengthening of synaptic activity resulting in high EPSP in post-synaptic neuronin response to chemical signal form this excitatory presynaptic input
It is prevalent in the HIPPOCAMPUS
What is long term depression?
It is weakening of synaptic transmisson
Describe the pathway for long term potentiation
- Rease of GLUTAMATE from pre-synaptic neuron
- Glutamate binds to AMPA&NMDA receptors
3.Binding opens AMPA receptor-channel
4.influx of sodium ions produces EPSP on post-synaptic neuron
5.Magnesium ions blocking at the NMDA receptor-channel is removed by sufficient depolarization
- Calcium ion influx via NMDA receptor-channel activates calcium ion second messenger pathway
- Second messenger pathway promotes insertion of additional AMPA receptors in post synaptic membrane hence THEREIS HIGH SENSITIVITY FOR GLUTAMATE
8.Second messenger pathway also TRIGGERS HIGH RELEASE OF RETROGADE PARACRINE LIKELY Nitric oxide
- Nitric oxide stimulates long lasting increase in glutamate release by presynaptic neuron.
State the importance
1. The hippocampus
2.
State the importance of the hippocampus in memory and learning
*It is prominent side for long term potentiation.
*Crucial for consolidation for long term memory
*involved in DECLARATIVE MEMORY: Choosing what memory of what people and things to remember
describe the two types of declarative memory
Semantic: memories of facts
Episodic: memories of events in our lives
Name a disease associated with hippocampal damage
Alzheimer’s disease
*memory loss
*problems with language
*disorientation
*mood swings
LONG TERM COMPLICATION includes dehydration and pneumonia in terminal stage
NO CURE
State the function of cerebellum in memory and learning
involved in procedural memories
which involve motor skills gained via training
They do not require CONSCIOUS RECALL
MOTOR AND SENSORY AREA
Ste the functions of prefrontal cortex in memory and learning
*WORKING MEMORY
*Responsible for EXECUTIVE FUNCTIONS WHICH allow on to decide what to do instead of just reacting to the situation at hand
Which part of the brain is responsible for declarative memories?
the hippocampus
Which part of the brain is responsible for procedural memories?
the cerebellum
Which part of the brain is responsible for working memory and executive functions?
The prefrontal cortex
Describe the MOA of NO in increasing GLUTAMATE release in presynaptic neuron
Nitric oxide is regarded as a neurotransmitter, but it is not a conventional one.
One of its actions occurs at NMDA receptors, which bind the conventional neurotransmitter, glutamate.
Glutamate binding to NMDA receptors at the synapse causes Na+ inflow into the post synaptic cell, starting an action potential.
At the same time Ca++also enters the cell, activating nNOS via calmodulin, generating nitric oxide.
This nitric oxide diffuses into cells around, including the presynaptic nerve ending.
Here it causes production of cGMP and activation of protein kinase G.
This stimulates production of glutamate containing vesicles in the nerve ending, making this particular neural pathway more likely to fire in response to a future stimulation. This strengthening of neural pathways which have transmitted once is thought to be a basis of a form of short term memory
Describe the anatomical that happen in brain due to ageing
there is a reduction in brain size,
a reduction in number of neurons,
probably a decrease in blood flow,
and a decrease in numbers of interconnections and synapses between cells.
Describe the biochemical changes within the cells in the brain due to ageing
A granular pigment called lipofuscin accumulates – its function is not known
Neurofibrillary tangles form within cells and amyloid plaques form between cells, particularly in areas (like the hippocampus) concerned with memory processing. Exactly what they do to cellular function is not clear but they are found at postmortem in brains of patients with dementia.
Describe Synaptic plasticity of brain and ageing.
It should be noted that although loss of brain cells on aging is inevitable, synaptic plasticity still occurs
It has been observed that animals kept in stimulating environments develop 25% more synapses than less stimulated animals.
This should probably be a guiding principle for any physician looking after older people – stimulation by intellectual activity cannot halt the degeneration of aging, but it can delay it.
