WEEK 3 (Synapses and Neural Integration) Flashcards
What are the stages of a chemical synapse?
- Action potential arrives at axon terminal of presynaptic neuron
- Voltage-gated Ca2+ channels open and Ca2+ enters the presynaptic neuron
- Ca2+ signals to neurotransmitter vesicles
- Vesicles move to the membrane and dock and Neurotransmitters released via exocytosis
- Neurotransmitters bind to receptors that are an integral part of chemically gated channels on subsynaptic membrane of postsynaptic neuron which opens the receptor-channel
- Signal initiated in postsynaptic cell since binding to receptor channels alters the ion permeability and potential of the postsynaptic neuron
What are the two types of synapses?
Electrical synapses and Chemical synapses
What is an electrical synapse?
Where two neurons are connected by gap junctions which allow charge carrying ions to flow directly between the two cells in either direction.
What is distinguishable about electrical synapses?
- extremely rapid
- connection is “on” or “off” and is unregulated
- action potential in one neutron always leads to an action potential in the connected neuron
- not as common as chemical synapses in the nervous system
In which muscle are gap junctions more numerous in?
Smooth muscle and cardiac muscle
Where are electrical synapses typically found?
Among populations of neurons where synchronisation of activity is paramount
What is a chemical synapse?
When a chemical messenger transmits information one way across a space separating the two neurons. It involves a junction between an axon terminal of one neuron (presynaptic neuron) and the dendrites/cell body of a second neuron (postsynaptic neuron)
Describe the anatomy of a chemical synapse
- Axon terminal of the presynaptic neuron ends in a slight swelling called the SYNAPTIC KNOB
- Synaptic knob contains SYNAPTIC VESICLES which store a chemical messenger (neurotransmitters) that has been synthesised and packaged by presynaptic neuron
- POST SYNAPTIC’s action potentials are propagated away from the synapse
- Space between the presynaptic and postsynaptic neurons is called the SYNAPTIC CLEFT
Why is the action potential passes chemically and not electrically in a chemical synapse?
The synaptic cleft is too wide for the direct spread of current from one cell to the other which prevents action potentials from electrically passing between the neurons
What is Multiple Sclerosis (MS) and what are the symptoms?
An autoimmune disease in which nerve fibres in various locations throughout the nervous system lose their myelin due to the body’s defence system attacking the myelin sheath surrounding myelinated nerve fibres
Symptoms depend on the extent and location of myelin damage and axon degeneration. They include fatigue, visual problems, tingling and numbness, muscle weakness, impaired balance and coordination and gradual paralysis
What is the physiology behind Multiple Sclerosis (MS)?
- Loss of myelin slows transmission of impulses in the affected neurons
- A hardened scar (sclerosis) forms at multiple sites of myelin damage which interferes with/eventually blocks action potentials in underlying axons
- Inflammatory phase sets off a degenerative phase
How is Multiple Sclerosis (MS) treated?
- Drugs that suppress immune attack on myelin
- Physical therapy
- Muscle relaxants
- Drugs to promote remyelination
- Vaccine that calms myelin-attacking immune cells
What is the difference between axons in the peripheral nervous system (PNS) and axons in the central nervous system (CNS)?
Cut axons in the peripheral nervous system (PNS) can regenerate whereas those in the central nervous system (CNS) cannot
Describe the stages of regeneration of Peripheral axons
- Detached part of axon degenerates & surrounding Schwann cells phagocytise the debris
- Schwann cells remain and form a regeneration tube that guides regenerating nerve fibre to its proper destination
- Remaining part of axon connected to the cell body starts to grow and move forward within the Schwann cell column by amoeboid movement
- Growing axon tip moves forward guided by a chemical secreted into the regeneration tube by Schwann cells
What are the fibres in the CNS myelinated by?
Oligodendrocytes
What inhibits the regeneration of CNS axons?
Oligodentrocytes surrounding the CNS axons synthesis proteins that inhibit axonal growth
How is the chemical synapse designed for the synapse to only operate in one direction from presynaptic to postsynaptic neuron?
The presynaptic terminal releases the neurotransmitter and the sub synaptic membrane of the postsynaptic neuron has receptor-channels for the neurotransmitter
What are the two types of synapses depending on the resultant permeability changes?
Excitatory & Inhibitory
What type of receptor channels are involved in excitatory synapses?
The receptor channels to which the neurotransmitter binds are nonspecific cation channels that permit simultaneous passage of Na+ and K+
Describe the stages of an excitatory synapse
- channels open in response to neurotransmitter binding which increases permeability to both of the ions at the same time
- electrochemical gradient causes Na+ to move into postsynaptic neuron and K+ to move out
- a larger number of Na+ moves in compared to K+ moving out which results in the net movement of cations into cell
- Inside of membrane is now slightly less -ve which produces a small depolarisation of postsynaptic neuron
What does the number of ions diffusing through an open non-specific cation channel depend on?
The ions’ electrochemical gradients
Why isn’t one excitatory synapse enough to depolarise the postsynaptic neuron?
Too few channels are involved at a single synaptic site to permit adequate ion flow to reduce the potential to threshold
What is the correlation between an excitatory synapse and an action potential?
The small depolarisation makes the postsynaptic neurons membrane more ‘excitable’ by bringing the membrane closer to threshold, increasing the likelihood that threshold will be reached
What is the name of the change in postsynaptic potential occurring at an excitatory synapse?
Excitatory postsynaptic potential (EPSP)
What is the difference between an excitatory synapse and an inhibitory synapse?
EPSP is activated by an excitatory presynaptic input and brings the postsynaptic neuron closer to threshold potential and an IPSP is activated by an inhibitory presynaptic input and moves the postsynaptic neuron farther from threshold potential
What is the name of the small hyper polarisation of the postsynaptic cell?
Inhibitory postsynaptic potential (IPSP)
What are the stages of an inhibitory synapse?
- Binding of a neurotransmitter with its receptor-channels increases the permeability of the sub synaptic membrane to either K+ or Cl-
- more K+ leaves the cell (efflux) and Cl- enters the cell due to electrochemical gradient
- movement causes a small hyper polarisation which brings the membrane potential farther from threshold
- membrane is now less ‘excitable’, inhibited and is harder to bring to threshold by excitatory input
What is the difference between the membrane channels in graded potentials and in action potentials?
graded potentials are produced by the opening of chemically gated channels and action potentials are produced by the opening of voltage-gated channels
How can one neurotransmitter produce EPSP in one synapse and IPSP in another synapse?
Different permeability changes occur in response to binding of the same neurotransmitter to different postsynaptic neurons
What are the two neurotransmitters that can be simultaneously released from the same synaptic vesicle to control activities with complex movements?
Glycine and GABA
What is Acetylcholine and what is its function?
It is synthesised from choline and acetyl CoA
FUNCTIONS:
- It is a major neurotransmitter in the peripheral nervous system
- released from motor nerves that supply skeletal muscle
- released from parasympathetic nerves that supply smooth muscle, cardiac muscle and exocrine glands
- also acts in the central nervous system
(EXCITATORY IN SKELETAL MUSCLE & INHIBITORY IN HEART)
Define Biogenic amines ‘Monoamines’
Amines each derived from a single amino acid
What is Norepinephrine and what is its function?
It is a catecholamine made from tyrosine
FUNCTIONS:
- Important in the PNS
- released from sympathetic nerves that supply smooth muscle, cardiac muscle and exocrine glands
- acts in CNS in pathways regarding memory, mood, emotions, behaviour, sensory perception, sleep and muscle movements
(EXCITATORY)
What is dopamine and what is its function?
A catecholamine made from tyrosine
important in “pleasure” pathways and muscle movements
(EXCITATORY AND INHIBITORY)
What is serotonin and what is its function?
An indoleamine made from tryptophan
Acts in CNS in pathways involving mood, emotions, behaviour, appetite, states of consciousness and muscle movements
(INHIBITORY)
What are the most abundant neurotransmitters?
Amino acids
What is the function of Glutamate?
The primary excitatory neurotransmitter in CNS; important in pathways involved with memory and learning
What is the function of Gamma-aminobutyric acid?
The primary inhibitory neurotransmitter in brain; often acts in same circuits as glutamate
What is the function of Glycine?
Primary inhibitory neurotransmitter in spinal cord and brain stem
Why are neurotransmitters quickly removed from the synaptic cleft?
Because as long as the neurotransmitter remains bound to the receptor-channels, the alteration in membrane permeability of EPSP and IPSP continues. For the postsynaptic neuron to be ready to receive additional messages from the same or other presynaptic inputs, the neurotransmitter must be inactivated or removed from the postsynaptic cleft after it has produced the appropriate response.
How can the neurotransmitter be removed from the synaptic cleft?
- Diffuse away from the synaptic cleft
- Inactivated by specific enzymes within the sub synaptic membrane
- Actively taken back up into the axon terminal by transport mechanisms in the presynaptic membrane
What can happen to the neurotransmitter once it is taken back up by the presynaptic neuron?
- It can be stored and released another time (recycled)
- Destroyed by enzymes within the synaptic knob
What is an example of a drug that interferes with the removal of specific neurotransmitters from synapses?
Selective serotonin reuptake inhibitors (SSRIs)
It is used to treat depression since it prevents the reuptake of serotonin which prolongs its action
What is distinguishable about graded potentials?
- Varying magnitude
- Have no refractory period
- Can be summed
What is the grand postsynaptic potential (GPSP)?
a composite of all EPSPs and IPSPs occurring around the same time
What is temporal summation?
The summing of several EPSPs occurring very close together in time because of successive firing of a single presynaptic neuron
How does the refractory period correlate to EPSPs causing an action potential?
Because graded potentials do not have a refractory period, the second EPSP can add to the first (as long as it hasn’t died down yet) bringing the membrane to threshold and initiating an action potential in the postsynaptic neuron
What is the amount of neurotransmitter released and the resultant magnitude of the change in postsynaptic potential directly related to?
The frequency of presynaptic action potentials
What is spatial summation?
The summation of EPSPs originating simultaneously from several presynaptic inputs
What happens when an excitatory and an inhibitory input are simultaneously activated?
The EPSP and the IPSP cancel each other out and the postsynaptic membrane potential remains close to resting potential
What are the dendrites’ function?
Primary processors of incoming information
Only if an __________ presynaptic signal is reinforced by other supporting signals through summation will the information be passed on to deliver a response to the stimulus
excitatory
What is the difference between an electrical synapse and a chemical synapse?
In a chemical synapse many factors can influence the generation of a new action potential in the postsynaptic cell
Describe the stages of urination regarding EPSP
- As the bladder fills with urine and becomes stretched, a reflex is initiated that produces EPSPs in the postsynaptic neutron responsible for causing bladder contraction
- As the bladder progressively fills, the frequency of action potentials progressively increases in presynaptic neuron
- When the bladder becomes sufficiently stretched the generated EPSPs are temporally summed to threshold
- The post-synaptic neuron undergoes an action potential that stimulates bladder contraction
Describe what happens to the bladder when it’s not the right time for urination to take place?
- Presynaptic inputs originating in higher levels of the brain responsible for voluntary control can produce IPSPs at the bladder postsynaptic neuron
- “Voluntary” IPSPs cancel out “reflex” EPSPs
- Postsynaptic neuron remains at resting potential which prevents the bladder from contracting and emptying despite it being full
What are Neuromodulators?
Chemical messengers that do not cause the formation of EPSPs or IPSPs but instead act slowly to bring about long-term changes that subtly modulate the action of the synapse
What are the properties of neuromodulators?
- Neural receptors that bind to neuromodulators are not located on the subsynaptic membrane
- Do not directly alter membrane permeability and potential
- Act at either presynaptic or postsynaptic sites
- Involved in long-lasting events (e.g learning and motivation)
What are the different neuromodulators?
- Neuropeptides
- Adenosine Triphosphate (ATP)
- Nitric Oxide (NO)
- Endocannabinoids
What are Endocannabinoids?
A group of lipid messengers that act in a way similar to the active component of cannabis or marijuana
What is distinguishable about Neuropeptides?
- Large molecules made up of anywhere from 2 to 40 amino acids
- Synthesised in the endoplasmic reticulum and Golgi complex of the neuronal cell body and transported through microtubular highways to the axon terminal
- Packaged in large dense-core vesicles
Dense-core vesicles undergo Ca2+ induced exocytosis and release _____________ at the same time that the neurotransmitter is released from synaptic vesicles
Neuropeptides
What is a neuropeptide that has no effect on neuronal activity and thus does not function as a neuromodulator?
Neurohormone
It is secreted by specialised neurons into the blood instead of being released into a synaptic cleft
Neuropeptides that serve as neuromodulators also include substances that function as _______________
Hormones
What is an example of a neuropeptide that function as neuromodulators?
Endogenous Opioids
They are internally produced morphinelike substances that dampen the sensation to pain
What is an example of neuropeptides that serve as neuromodulators that also function as hormones?
Cholecystokinin (CCK)
Released from the small intestine and causes the gall bladder to contract and release bile into the intestine. CCK also is a neuromodulator in the brain and causes the sensation of no longer being hungry
What is another means of depressing or enhancing synaptic effectiveness aside from neuromodulation?
Presynaptic inhibition or facilitation
What is the difference between presynaptic inhibition and presynaptic facilitation?
This occurs when a presynaptic axon terminal is innervated by another axon terminal and neurotransmitter released from terminal B binds with receptors on terminal A. The binding alters the amount of neurotransmitter released from terminal A in response to action potentials.
PRESYNAPTIC INHIBITION is when the amount of neurotransmitter released from A is reduced and PRESYNAPTIC FACILITATION is when the release of neurotransmitter is enhanced.
What is distinguishable about presynaptic inhibition?
Certain inputs to the postsynaptic neuron can be selectively inhibited without affecting the contributions of any other inputs
[the production of an IPSP would cancel out ALL the EPSPs attached to the postsynaptic cell whereas presynaptic inhibition allows only that ONE presynaptic neuron to be inhibited]
What are the mechanisms that some drugs influence the nervous system?
- altering synthesis, storage or release of a neurotransmitter
- modifying neurotransmitter interaction with the postsynaptic receptor
- influencing neurotransmitter reuptake or destruction
- replacing a deficient neurotransmitter with a substitute transmitter
What is the mechanism behind cocaine addiction?
- Blocks the reuptake of dopamine at presynaptic terminals by binding competitively with the dopamine reuptake transporter
- Dopamine remains in synaptic cleft for longer and “locks in” the feeling of pleasure
- Individual gets desensitised to the drug and becomes addicted
- Number of dopamine receptors in the brain is reduced and the individual experiences drug tolerance by needing higher doses to feel the same “high” and to avoid withdrawal symptoms
What are the mechanisms behind Tetanus toxin and Strychnine?
Tetanus toxin prevents release of GABA from inhibitory presynaptic inputs that terminate at neurons that supply skeletal muscles. Unchecked excitatory inputs result in uncontrolled muscle spasms which occur in jaw muscles early in the disease “Lockjaw syndrome” which progress to muscles responsible for breathing, leading to death.
Strychnine is a competitive inhibitor which prevents Glycine (an inhibitor transmitter) from binding with the presynaptic neuron to form IPSPs. Unchecked excitatory pathways lead to convulsions, muscle spascity and death.
What is the difference between convergence and divergence?
Convergence is when a single cell is influenced by thousands of other cells.
Divergence refers to the branching of axon terminals so that a single cell synapses with and influences many other cells.
