Neural Structure and Signaling (6/23/15) Flashcards
Neurons make up _____% of all CNS cells.
10%
Myelin _____ action potential speed.
Increases!
______ is the trigger zone for action potentials.
Axon hillock (Intial segment)
True or false, neurons are Terminally differentiated
True, they are non-dividing
What is the Soma of a neuron?
Contains the nucleus and is used for protein synthesis.
Where are vesicles stored?
Axon terminals
What are the 3 main classes of Neurons?
- Afferent = Sensory/Input transmit info to CNS
- Interneurons = Located within CNS and function as integrators and switches.
- Efferent = Motor/output Neurons transmit commands to effector cells. (cell bodies within CNS but axons project outside.
* SAME = sensory afferent/Motor Efferent
____ make up 90% of cells in CNS.
Glial Cells
What are the Gilal cells of the CNS?
Ogliodendrocytes and Microglia (Provide myelination)
What are the Gilal cells of the PNS?
Schwann cells (Provide myelination)
What is a Microgila?
(Glial cell) A macrophage like cell that has phagocytic role.
Has:
- Unreactive (resting state)
- Reactive state
What is an astrocyte?
A CNS Gilial cell that:
- Regulates extracellular fluid (Remove K+ and neurotransmitters) buffering role.
- Provide neurons metabolically (such as glucose)
- Surround brain capillaries (form blood-brain barrier)
Schwann cell provides myelin to ________.
One axon (Many schwann cells per axon)
Oligodendrocytes provide myelin to ______.
many axons
What Clinical condition is associated with Peripheral demyelination?
Guillian-Barre Syndrome (Demylenation of motor neurons)
Nerve damage
Describe the Neuron to Microglia interaction….
- Neuron keeps Microglia Unreactive with neuron glycoprotein CD200.
- Neuronal injury releases intracellular ATP inducing motility (Reactive)
- Microglia move to site of injury.
Describe the Microglia to Neuron interaction….
Not well understood, but they make physical contact with healthy neurons and are involved in “Pruning” unused dendrites.
______ is transport of material (Nutrients, enzymes, neurotransmitters) away from the cell body down the axon.
Anterograde transport
- Fast rate around 400mm/day (Neurotransmitter vesicles)
- Slow transport 2-2.5 mm/day (Structural proteins)
_______ is transport of materials towards the cell body of neuron.
Retrograde transport
- Fast 400 mm/day (motor protiens “Dyneins”)
Viruses are commonly transported via _______.
Retrograde transport
- Herpes
- Rabies
- Polio
_______ plays a large role in nerve regeneration.
Axonal transport
- Retro & Antero
Nerve growth and regeneration in CNS vs PNS, Go!
CNS = neurons do not regenerate! Axons “Sprout” but do not reach targets due to Scar formation.
- Astroycytes also make Chondroitin sulfate proteoglycans that inhibit nerve growth.
PNS = axons DO regenerate here! Which is important for dental procedures such as extractions.
- Functional recovery can take place depending on severity.
What is a “Severe Nerve injury” and what is the response to it?
A severe nerve Injury tends to be close to the cell body in the Nerve trunk.
- We will see Anterograde and terminal degeneration of injured portion of neuron.
- Cell death may occur - at this point regeneration is impossible.
- Transganglionic degeneration = degeneration of central process of axon.
- Transsynaptic Degeneration = Induces degeneration on 1st central neuron that cell synapsed on.
What is a “Less severe Nerve injury” and what is the response to it?
A less severe nerve injury is further away from the cell body.
* All that happens here is Anterograde and Terminal degeneration (Terminal degeneration is the degeneration of axon terminals specifically)
Describe the Roll of Schwann cells in regeneration…..
Schwann cells produce Laminin for substrate for regenerating axons.
They also secrete NGF (nerve growth Factor) that is transported to the Ganglion body.
What does NGF (Nerve growth factor) do?
It regulates gene expression and promotes sprouting.
How does Collateral sprouting occur?
NGF moves via Retrograde Transport and then collaterals sprout off of axon since NGF promotes sprouting.
Do teeth allow rein nervation of nerves?
No!
If you cut one side of the trigeminal nerve, what happens?
Ipsilateral numbness and increased midline sensitivity (Due to collateral sprouting)
T or F, nerve regeneration gets better as you get older.
False, it gets worse.
How can you classify Synapses?
Chemical Vs Electrical
Excitatory Vs Inhibitory
What are the types of Chemical Synapses?
Axo-somatic
Axo-dendritic
Axo-axonic
What are the location of Synapse receptors?
Postsynaptic
Presynaptic
Autorecptors = respond to released ligand.
IMPORTANT! What are the Basic steps to Synaptic transmission?
- AP reaches axon terminal
- Voltage gated Ca++ channels open
- Calcium exits the terminal
- Neurotransmitter is released and diffuses into cleft
- Neurotransmitter binds to postsynaptic receptors
- Neurotransmitter is removed from cleft via repute and enzymes.
What is Synaptogamin?
Ca++ sensitive docking proteins for vesicle fusion and release.
Describe Synaptic Integration and the two types of summation….
A post synaptic potential is only about 0.5mV so it is the combined effects excitatory and inhibitory synaptic input that determines whether threshold is reached.
- Temporal summation = adding together of PSP’s from one synaptic contact over time.
- Spatial summation = Adding together of PSP’s produced by DIFFERENT synapses.
What are the sites of action and methods of action of drugs at the synaptic junction? (7)
A drug might:
- Increase leakage of neurotransmitter from vesicle to cytoplasm, exposing it to enzymatic breakdown.
- Increase neurotransmitter release into cleft.
- Block transmitter release
- Block transmitter reuptake
- block cleft transmitter that metabolize transmitter.
- bind to receptor on postsynaptic membrane to block or mimic transmitter action.
- inhibit or stimulate second messenger activity within postsynaptic cell.
What is the difference between neurotransmitters (Classical) and Neuromodulators?
Neurotransmitters = release at synapse and have a very rapid effect (msecs) and acts on postsynaptic cell to produce EPSP or IPSP
Neuromodulators = often co-released with neurotransmitters and may act on pre-synaptic cell to alter synthesis, release, uptake or metabolism of neurotransmitters. Actions can involve changes in protein synthesis or enzyme activity and can be much slower in action (min-days)
*Some ligands can have both neurotransmitter and neuromodulator functions!
Tell me about Acetylcholine….
Acetylcholine is a neurotransmitter/modualtor that is synthesized from acetyl co-enzyme A and choline by choline acetyltransferase in synaptic terminal. The action is stopped by diffusion and degradation (By acetylcholinesterase)
*Choline re-uptake by presynaptic neurons
What neurons release Acetylcholine?
- motor neurons
- Neurons in nucleus basalis and pons
- Preganglionic sympathetic & Parasymp. neurons
- All post ganaglionic parasymp. neurons
What are the 2 main types of Acetylcholine receptors?
- Muscarinic receptors = Mostly found in CNS
- Binding ACh trigger G protein that open or close ion channels (can be either depolarizing or hyper-polarizing) - Nicotinic receptors = Relatively few in CNS
- ACh binding opens ion channels within receptor (Channel permeable to Na+ and K+)
Ex. = neuromusular junciton: depolarizing
What can block muscarinc receptors?
atropine
Although muscarine receptors are mainly found in the CNS what are the exceptions?
parasympathetic postganglionic synapse (such as salivary glands)
What can block Nicotinic receptors?
curare (Neuromuscular junction)
What are the 2 ACh diseases?
Myasthenia gravis = nicotinic receptor is destroyed
- autoimmune disorder where body makes antibodies to nicotinic receptors.
- Characterized by muscle weakness
- Treated with acetylcholinesterase
Alzheimers disease = most common form of dementia
- many neuron populations involved
- loss of neurons in nucleus basalis leading to decrease in cholinergic activity in cortex.
What is a Biogenic Amine?
Biogenic Amines are neurotransmitters/modualtors that are synthesized from amino acids. They include Catecholamines such as: dopamine, norepinephrine and epinephrine *all synthesized from aa tyrosine
What is the lifecycle of a Catecholamine (Biogenic amine)?
- Synthesis = presynaptic terminal stored in vesicles.
- Release = Ca++ dependent
- Termination of Action = presynaptic neuron re-uptake and then degradation via monoamine oxidase (MAO)
Where are receptors for catecholamine and other biogenic amines found?
They are found extensively through the CNS (although he neurons that synthesize the ligand are found in very limited locations) and the receptors are almost elusively G-protein coupled receptors.
What do Catecholamines and other biogenic amines do?
They are involved in many functions (and dysfucntions) such as:
- Arousal/attention
- Feeding
- movement
- cognitive function
- Parkinsons disease
- Depression
- Schizophrenia
Tell me about Catecholamine: Dopamine…..Where is it found and what does it do?
Found in:
Ventral segmental area = associated with reward and addiction (cocaine and amphetamines prolong dopamine action at synapse)
Substantial nigra = associated with motor system (loss of dopamine associated with Parkinsons disease)
*There are 2 mains groups of dopamine:
D1 = activates adenylate cyclase
D2 = inhibits adeylate cyclase (leading to hyper-polarization)
*Many drugs block D2 receptor such as antidepressants can cause Tardive dyskinesia
What is Tardive Dyskiesia?
Oral sterotopy
-20-50% incidence in patients taking dopamine blocking drugs.
Most commonly presented as rhythmic oral moments (Buccal-lingual)
*D2 receptors implicated.
Tell me about Catecholamine: Norepinephrine….Where is it found and what does it do?
Found in:
Locus cereals = attention and sleep
Other brainstem groups = autonomic and homeostatic functions
*Often referred to as adrenaline
Norepinephrine neurons include….
sympathetic postganglionic neurons (and some CNS)
What are the receptors for Norephinephrine?
Many!
Alpha receptors:
- A1 = intracellular release Ca++ (excitatory)
- A2 = opening K+ channels or blocking Ca++ (inhibitory)
Beta receptors (B1, 2, and 3) open Ca++ channels *Thus we see NE can have many different effects based on the receptor.
Tell me about Catecholamine: Serotonin….Where is it found and what does it do?
Found in: several discrete CNS populations
Rostal raphia nuclei = sleep, mood, homeostatic function
Caudal raphe nuclei = sensori-motor function
- Serotonin is synthesized from tryptophan and is involved in functions ranging from sensorimotor to cognitive function (mood).
- 16 receptor subtypes
- most are G-protein coupled
- 5-HT synapses target of mood altering drugs.
Tell me about Catecholamine: Histamine….Where is it found, and what does it do?
Histamine is derived from AA histidine
- found in only small populations of hypothalamic neurons.
- G-protein coupled receptor
- involved in sleep/wakefulness
What are the main Excitatory Amino Acid Neurotransmitters?
Glutamate and Aspartate *Glutamate is most common excitatory neurotransmitter.
How do Excitatory Amino Acid Neurotransmitters work?
They bind to several classes of ionotropic receptors:
- AMPA
- Kainate
- NMDA
- Receptors have channels permeable to Na+, K+ and Ca++
*Also a classy of metabotropic receptors = G-protein receptor.
What is the NMDA receptor and what is its functions/characteristics?
N-Methyl-D-Aspartate receptor is involved in functions that LAST such as:
- memory formation
- chronic pain
- Excitotoxicity: excessive cell excitation = cell death (epilepsy, trauma, stroke)
- Neuron cell death from Ca++ reaching toxic levels
NMDA is the neurotransmitter of Synaptic mechanism of LONG TERM POTENTIATION!
What are the Steps of NMDA mediated potentiation?
- High frequency AP’s in presynaptic cell
- Glutamate is released
- Glutamate binds to both channels
- Na+ entry depolarizes cell by 20-30 mV
- Depolarization removes Magnesium block from pore
- Ca++ enters pore and activates second messager system (Ca++ is the second messenger)
- Long lasting increase in glutamate receptors and sensitivity.
- Long lasting in glutamate synthesis and release.
What factors promote LTP?
- Phosphorylation of NMDA receptor
- permanent removal of Mg+ block - Calcium entry into cell via NMDA receptor
- phosphorylation of AMPA receptors
- Increase in number of AMPA receptors
- synthesis if retrograde messenger nitric oxide (NO) (Facilitates glutamate synthesis/release pre-synaptically)
What are the main Inhibitory Amino Acid Neurotransmitters?
GABA = Major inhibtory AA neurotransmitter in CNS.
Glycine = found mostly in the spinal cord, it opens Cl- channels and can be blocked by strychnine.
What are the two types of GABA (inhibitory AA neurotransmitter)?
GABAa = ionotropic receptor that opens Cl- channel (Cl- will flow into cell = hyper polarizing effect)
GABAb = Metobotropic receptor that opens K+ channel (K+ will flow out of cell = inhibition)
What disease is linked to GABA deficits?
Hunting Chorea = form of motor spasticity.
What happens if Inhibitory AA neurotransmitter Glycine gets blocked by strychnine?
It will block inhibition, which can cause uncontrolled excitation which can be fatal.
Tell me about Neuropeptides….
Neuropeptides are “classic” Neuromodulators
- over 80 identifed
- endogenous opioids = pain
- substance P = pain
- Neuropeptide Y = feeding
*Often co-released with other neurotransmitters.
They function as a neuromodualtor:
- Actions can last a long time
- Action is terminated by proteolysis and diffusion.
Can peptides be recycled or?
No they cannot be re-uptaken nor recycled
What does the neurotransmitter NO (Nitric oxide) do?
Can modulate neurotransmitter release such as GABA or Glutamate.
- Role in injury = excitotoxicity
- also plays role in numerous brain functions (Long term potentiation)
What does neurotransmitter ATP do?
- Usually excitatory (Taste)
- Usually co-released correlated with classical neurotransmitters.
What can drugs do at synapses? (7)
- Increase transmitter release into cleft (Amphetamine increase biogenic amine release)
- Block transmitter release
- Modulate transmitter sysnthesis (L-dopa increases Dopamine synthesis)
- Block transmitter repute (Cocaine blocks biogenic amine reuptake)
- Block enzymes that metabolize transmitters.
- Bind to postsynaptic ionotropic receptor (curare-nicotinic ACh receptor and Strychnine - glycine)
- Bind to postsynaptic g-protein coupled receptors (Atropine - muscarinic ACh receptor)
