Term
| Properties of dendrites vs. axons |
|
Definition
Dendrites - receptive
Axons - conductive |
|
|
Term
| What is the predominant neuronal morphology in the CNS? |
|
Definition
| Multi-polar neurons (multiple dendrites w/ 1 axon) |
|
|
Term
| Main 3 populations of glia in the CNS: |
|
Definition
Astrocytes
Oligodendrocytes
Microglia |
|
|
Term
| Normal cellular functions of astrocytes: |
|
Definition
Important for formation of the BBB in the CNS
End foot processes wrap around capillaries in CNS to make it selectively permeable |
|
|
Term
| Normal cellular functions of oligodendrocytes: |
|
Definition
Myelin making cells of the CNS
Myelin = living material |
|
|
Term
|
Definition
| Clean up cellular debris in the CNS via phagocytosis |
|
|
Term
| By what age have we developed our entire neuronal population in our brains? |
|
Definition
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Term
| Neurulation in the Mammalian Embryo |
|
Definition
First the NEURAL PLATE arises from the ectoderm of the developing embryo
Then, the two folds of the plate come together, meeting in the midline to form the NEURAL TUBE
On the borders of the neural tube, see NEURAL CREST cells |
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|
Term
| Cells arising from the neural tube vs. neural crest |
|
Definition
Neural Tube = gives rise to all neurons of the CNS + oligodendrocytes & astrocytes
Neural Crest = gives rise to the PNS and its associated glia |
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Term
| Which of the CNS glia do NOT originate from the neural tube? |
|
Definition
| Microglia (neural crest origin) |
|
|
Term
| Neuropathy from improper neural tube "zippering" |
|
Definition
Spinobifida - improper caudal zippering
Anencephalic - failure of tube to zip up rostrally; no cortex only brainstem |
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|
Term
| Where is sonic hedgehog protein (Shh) specifically expressed? |
|
Definition
| Cells of the FLOOR PLATE of the neural tube |
|
|
Term
| Where is the Noggin protein specifically expressed? |
|
Definition
| The ROOF PLATE of the developing neural tube |
|
|
Term
| Where are the roof plate / floor plate located respectively? |
|
Definition
Roof plate - dorsal midline of neural tube
Floor plate - ventral midline of neural tube |
|
|
Term
|
Definition
Develops UNDER the floor plate (ventral midline) in embryo
Powerful INDUCTIVE structure (induces NS development)
Drives differentiation of roof & floor plates
NON-Neural TISSUE |
|
|
Term
| What kind of tissue is the notochord made of? |
|
Definition
|
|
Term
| What is the function of the notochord? |
|
Definition
Inductive structure -> induce NS development
Drives the differentiation of the roof and floor plates in the embryo |
|
|
Term
| In the adult human SC, where are the motor & sensory neurons located |
|
Definition
Sensory - dorsal (cell bodies from the roof plate)
Motor - ventral (cell bodies from the floor plate) |
|
|
Term
| Where do the somae of sensory neurons develop? |
|
Definition
| Near the roof plate (b/c sensory neurons arise dorsally from the SC) |
|
|
Term
| Where is NETRIN synthesized? |
|
Definition
| Specifically near the floor plate |
|
|
Term
| Actions of Netrin on developing SENSORY NEURONS |
|
Definition
Exerts an attractive force -> directional axon growth towards the floor plate
Positive growth factor for directional sensory axon growth |
|
|
Term
| Where do the somae of motor neurons develop? |
|
Definition
| Near the floor plate - in adult human SC, motor neurons arise ventrally from the SC |
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|
Term
| Effects of Netrin on the directional growth of MOTOR neurons: |
|
Definition
Netrin is produced by the floor plate itself (same area where somae of motor neurons are located)
Netrin is REPULSIVE to the axons of motor neurons -> causes axons of motor neurons to leave the SC |
|
|
Term
| What are the characteristics of netrin knockout mice: |
|
Definition
Sensory neurons develop, but axons do not grow in a directional manner (not attracted towards floor plate)
Motor neurons develop, but axons have odd growth patterns and remain w/in CNS |
|
|
Term
| Is NETRIN neurotrophic or neurotropic? |
|
Definition
| It is NEUROTROPIC - drives directional axon growth |
|
|
Term
|
Definition
Holoprosencephaly
Medulloblastoma
Basal Cell Carcinoma |
|
|
Term
|
Definition
Malformation of forebrain - prosencephalon (forebrain) fails to develop into 2 hemispheres
Also disrupts midline facial structures (e.g. cyclopean eye)
Deletion/missense mutations of Shh gene |
|
|
Term
|
Definition
Childhood brain tumor; abnormal neurogenesis & cell migration in CEREBELLUM
Shh normally produced by Purkinje cells in cerebellum to act as mitogen to cause granule cell precursor division - these precursors form cerebellar neurons
Elevated Gli1 levels (oncogene product); normally Gli1 is regulated by Shh signalling
Need Shh interaction with PTC receptor to keep Gli1 levels in check - 9% of pt's have PTC loss of function PTC mutations |
|
|
Term
|
Definition
Carcinoma of the skin; most common Shh related disorder
Responsive to Shh signaling modification
GORLIN SYNDROME - nevoid basal carcinoma; caused by loss of function of PTC receptor; commonly co-morbid basal cell carcinoma & medulloblastoma |
|
|
Term
| Contrast the 3 different Shh related disorders: |
|
Definition
Holoprosencephaly - morphogenetic effects of los of Shh signalling (failure of hemisphere formation)
Medulloblastoma - Shh signalling deficit causes disregulation of cell proliferation
Basal Cell Carcinoma - Shh signalling deficit causes lack of differentiation (cancer formation) |
|
|
Term
|
Definition
Part of developing brainstem; are EXPRESSION DOMAINS of hox genes; appear as 7 transient bulges in the brainstem
Hox genes give rise to cranial nerve nuclei |
|
|
Term
| During mammalian embryogenesis where does the peak of neurogenesis occur? |
|
Definition
| Near the ventricular zone (around the ventricles); this is the innermost area surrounding the neural tube |
|
|
Term
| What aids in migration of neuroblasts through the developing cortex? |
|
Definition
|
|
Term
| What are radial glial cells and how do they function? |
|
Definition
Extend from ventricular zone through intermediate zone into cortical zone
Act as a "highway" for migrating neuroblasts
Use reelin & DCX as association proteins
Also, connexins forming hemichannels & gap junctions play a role in the neuroblast-glial association |
|
|
Term
| Mutations in Reelin and DCX cause... |
|
Definition
Reelin = enlarged ventricles & diminished subcortical white matter
DCX = smooth brain (no sulci/gyri = lissencephaly) |
|
|
Term
| What are two different methods of neuronal migration? |
|
Definition
Within the cortex -> radial glial cells associate with neuroblasts to provide a scaffolding for them to travel along
Growth factor/receptor interactions for longer distances -> for example, GDNF guiding ENCC migration through the gut |
|
|
Term
| Processes occurring in the developing NS: |
|
Definition
Neuronal + glial development (from neural tube/crest)
Neuroblast migration
Neuroblast differentiation to the given population (expression of hox genes)
Directional axonal elongation (neurotropic effects) |
|
|
Term
| Where are motor neurons "produced" in the spinal cord? |
|
Definition
| In the ventral aspect (rostral), arising from the floor plate of the neural tube |
|
|
Term
| What dictates the final # of motor neurons (i.e. what regulates motor neuron survival)? |
|
Definition
|
|
Term
| What happened to sympathetic ganglia when mice were treated w/ NGF-antibodies? |
|
Definition
| They died from loss of sympathetic neurons (shows neurotrophic abilities of NGF) |
|
|
Term
| What did early NGF experiments show to be the two main properties of the growth factor? |
|
Definition
Regulate neuronal survival
Directionally affect axonal growth of sympathetic & sensory neurons |
|
|
Term
| What occurred when Montalcini grafted the sarcoma 180 cell line onto the chick embryo? |
|
Definition
| Saw hyperproliferation of both sensory and sympathetic ganglia -> both had to be responding to some sort of growth factor from the tumor line |
|
|
Term
|
Definition
Shown in vitro; placed sensory ganglia in a petri dish w/ NGF
Ganglia send out neurites in ALL directions w/in the dish; showed positive exposure to added NGF |
|
|
Term
| Experimental results of NGF, BDNF & NT-3 w/ DRG, NG, SG |
|
Definition
NGF -> saw neurite outgrowth in DRG & SG
BDNF -> saw neurite outgrowth in DRG & NG
NT-3 -> saw neurite outgrowth in all 3 |
|
|
Term
| Experimental results of NGF, BDNF & NT-3 w/ DRG, NG, SG |
|
Definition
NGF -> saw neurite outgrowth in DRG & SG
BDNF -> saw neurite outgrowth in DRG & NG
NT-3 -> saw neurite outgrowth in all 3 |
|
|
Term
| 3 different NGF experiments by Montalcini |
|
Definition
Sarcoma 180 graft -> hyperproliferation of S & S ganglia
Halo effect of sensory ganglia w/ NGF in vitro
Application of NGF-antibodies to mice causing atrophy of sympathetic ganglia |
|
|
Term
| Neurotrophic VS. Neurotropic |
|
Definition
Neurotrophic = survivability of neurons
Neurotropic = directional axon/neurite growth |
|
|
Term
| What determines NT specificity to neuron populations? |
|
Definition
| The receptors expressed by the neurons |
|
|
Term
| What are the binding properties of the different NT's with the Trk receptors? |
|
Definition
NGF - binds specifically to TrkA
BDNF - binds specifically to TrkB
NT-3 - predominately binds to TrkC; low affinity binding to TrkB also |
|
|
Term
| What are the positive cellular effects seen after NT binding to a Trk receptor? |
|
Definition
Cell proliferation, cell survival, neurite outgrowth, activity dependent plasticity
All occurs via 2nd messenger cascades (beginning from intracellular TK motif) |
|
|
Term
| If you exposed a certain ganglia to NGF and did not see any neurite outgrowth what is the most likely reason for this? |
|
Definition
| Likely due to the fact that the neuron does not express TrkA, therefore it cannot bind the NGF present |
|
|
Term
| What are 2 caveats of receptor expression & signaling? |
|
Definition
Peripheral glia express only p75NTR and NO Trk receptors - if p75 exerts negative effects, how do these cells survive?
Almost all neurons expressing a Trk receptor also express p75, how do they both bind the same NT and signal opposite cellular mechanisms? |
|
|
Term
| What are the ratios of p75 to Trk receptors on a cell that expresses both of them? |
|
Definition
p75 is ALWAYS more abundant - may aid in its "sequestration function"
More abundance = more binding (despite low affinity) |
|
|
Term
| What tissues near the skin produce the various NT's? |
|
Definition
NGF - from free nerve endings
BDNF - from Merkel discs (vibration & touch)
NT-3 - from muscle spindles (sense stretch)
NT4/5 - from hair follicles |
|
|
Term
| How does the brain differentiate sensory afferents coming back to the spinal cord? |
|
Definition
| They have differential localization both CENTRALLY (w/in spinal cord) and PERIPHERALLY (neurotropic effects of the target-derived growth factors) |
|
|
Term
| Where are NGF/TrkA axons localized and where are NT-3/TrkC axons localized at the periphery? |
|
Definition
NGF/TrkA axons - localized near the skin (free nerve endings)
NT-3/TrkC axons - localized near skeletal muscle (muscle spindles) |
|
|
Term
| Why are proprioceptive neurons larger than sensory neurons for pain/temperature? |
|
Definition
| Because they need their impulses to travel more quickly to the processing centers of the CNS |
|
|
Term
| Characteristics of TrkC/NT-3 knockouts: |
|
Definition
NO development of proprioceptive axons (from muscle spindles)
Mouse is not viable and dies immediately |
|
|
Term
| Characteristics of TrkA/NGF knockout mice: |
|
Definition
NO development of pain neurons (sensory) or sympathetic neurons (b/c of neurotrophic actions of NGF)
Survive about a week then die |
|
|
Term
| Characteristics of TrkB/BDNF knockout mice: |
|
Definition
Loss of vibration/touch neurons from skin (BDNF is Merkel disc derived)
ALSO, see loss of facial MOTOR NEURONS
Mice cannot suckle b/c of motor neuron loss and starve to death
Therefore, BDNF affects both SENSORY AND MOTOR neurons |
|
|
Term
| What neuronal populations are affected in NGF/BDNF/NT-3 knockouts (or knockouts of their respective receptors)? |
|
Definition
NGF/TrkA - loss of sensory and sympathetic neurons
BDNF/TrkB - loss of sensory and facial motor neurons
NT-3/TrkC - loss of proprioceptive (sensory) neurons |
|
|
Term
| Campenot chamber experiment: |
|
Definition
NGF in all compartments = equal neurite outgrowth to both sides (2 & 3)
NGF only in compartment 3 = neurite outgrowth in 3 (neurotropic), BUT still get survival of axons in compartment 1 (neurotrophic)
Survival of axons is due to retrograde transport of NGF down the axon to the soma AND by signalling from the axons in 3 following NGF binding |
|
|
Term
| Inhibitory effects of oligos post-SCI: |
|
Definition
See oligodendrocyte cell death & myelin degeneration -> leads to formation of MYELIN DEBRIS in CNS (CNS-myelin is inhibitory to axon regrowth)
Also, oligodendrocytes release inhibitory factors as they die |
|
|
Term
| Inhibitory effects of astrocytes post-SCI: |
|
Definition
Form a glial scar at the site of injury - physical and chemical barrier to prevent axonal regrowth
Scar is formed because of compromised BBB at the site of injury |
|
|
Term
| Inhibitory effects of microglia following SCI: |
|
Definition
| After injury, secrete inhibitory cytokines + are hyperactivated (inhibitory to central axon regrowth) |
|
|
Term
| Why are axons able to regrowth peripherally but not centrally? |
|
Definition
| Because of the POSITIVE ENVIRONMENT of the PNS following injury (Schwann cells and macrophages allow for axons to regrow) |
|
|
Term
| What are the positive effects in the PNS environment after injury that allow for axonal regeneration? |
|
Definition
Myelin debris formed at injury site attracts macrophages to clear the debris (cannot happen in CNS b/c of BBB) - less debris = less inhibition
See expression of growth related genes in the somae of the injured axons (environmentally triggered)
Schwann cells act as positive substrates for axonal regrowth; promote many growth factors to signal positive growth |
|
|
Term
| Why will direct Schwann cell grafts into the CNS not allow for central axonal regeneration? |
|
Definition
| Because not even the Schwann cells can survive alone in the toxic environment of the CNS post-injury |
|
|
Term
| Why was the sciatic nerve graft placed under the scalp? |
|
Definition
| So its BV's could anastomose with the BV's of the scalp to give the graft a vascular supply |
|
|
Term
| What happened to the regenerating retinal axons that traveled through the sciatic nerve graft when they reached the superior colliculus? |
|
Definition
They STOPPED growing!
Likely occurred because the axons re-entered the toxic environment of the CNS (b/c the graft required a lesion to the CNS, the usual culprits contribute to the toxicity here) - inhibitory to axonal regrowth |
|
|
Term
|
Definition
Able to give rise to neurons, oligodendrocytes & astrocytes in culture
Taken from lateral ventricular walls by accident
Behave like STEM CELLS |
|
|
Term
| How do the neurospheres of the anterior SVZ reach their final destination? |
|
Definition
| They travel to the OLFACTORY BULB via the ROSTRAL MIGRATORY STREAM |
|
|
Term
| What do the neurospheres end up becoming in the olfactory bulb? |
|
Definition
| They form 2 distinct populations of olfactory neurons (maintain plasticity of olfactory bulb throughout life) |
|
|
Term
| Parkinson's & olfactory neurons: |
|
Definition
In early stages of Parkinson's often see a deficit in the sense of smell
May be something wrong with rostral migratory stream |
|
|
Term
| Similarities in neurogenesis in the embryonic AND adult mammalian brain... |
|
Definition
| The main site of neurogenesis in both is near the ventricles (around ventricles in embryo; anterior SVZ in adults = stem cell niche) |
|
|
Term
| Where are the two stem cell niches located in the adult mammalian brain? |
|
Definition
Anterior SVZ (lateral wall of lateral ventricle)
Hippocampus - basal aspect of granular layer of dentate gyrus |
|
|
Term
| What two characteristics do stem cells need to be able to possess: |
|
Definition
- Need to give rise to new cells
- Need to give rise to more stem cells (renew population of niche) |
|
|
Term
| Stem cell niche in the hippocampus & their final migratory location/cell type |
|
Definition
Niche is located in the basal aspect of the granule layer of the dentate gyrus of the hippocampus
Post-mitotic neuroblasts move into population of granular neurons -> integrate as GABAergic interneurons |
|
|
Term
| How does the rat learn the location of the platform in the Morris Water Maze test? |
|
Definition
| Visual cues from the walls of the room the maze is placed in |
|
|
Term
| Morris water maze test w/ a rat w/ a hippocampal lesion (naive vs. learned) |
|
Definition
Naive = takes the rat really long to learn task
Learned = rat appears to "forget" where the platform is |
|
|
Term
| What is the effect of enriched environments on rats? |
|
Definition
Rats growing up in enriched environments (more toys & littermates) perform better on learning/memory tasks AND have a larger population of hippocampal neurons
See both anatomical and behavioral evidence that enriched environments are beneficial |
|
|
Term
| What is the primary site of central NGF synthesis? |
|
Definition
|
|
Term
| Criteria for axonal regeneration |
|
Definition
Axon extends from CNS into non-CNS environment (glial scar); goes from host CNS into non-host graft/implant
Axon must take an unusual path through its environment
Axon must have an unusual phenotype for axons of its kind
Axon must be tipped with a growth cone
Axon cannot grow faster than what can be accounted for by plausible rates
Axon must originate at or near the site of lesion |
|
|
Term
|
Definition
Migration of Schwann cells into the SC following SCI
Do not last for long in the toxic environment of the CNS though |
|
|
Term
| Olfactory Ensheathing Cells |
|
Definition
| Type of glia found in the nasal cavity; wrap around axons from olfactory epithelia to olfactory bulb (provide protection for axons in harsh conditions w/in nasal cavity) |
|
|
Term
| Why were OEC's chosen as decent candidates for populating the cystic cavity formed at the site of SCI? |
|
Definition
Because in their normal environment they serve as a form of protection in a harsh environment; essentially, the same thing is what we want for the cavity
Need to be able to "protect" regenerating axons from the toxic CNS environment |
|
|
Term
| What markers are expressed by both OEC's and Schwann cells? |
|
Definition
| GFAP and S100 -> cannot conclusively use these as markers for either one because presence of either could be due to presence of both cell types |
|
|
Term
| Aside from the lacZ enzyme expression, how else could OECs be labeled and identified post-implantation? |
|
Definition
Used calponin & SMA as phenotypic markers - both were expressed before and after implantation by the tunnel/fascicle forming cells
THEREFORE, OEC's remain unique following implantation |
|
|
Term
| How do OECs and Schwann cells function as a team in helping axonal regrowth? |
|
Definition
OECs - provide protection
Schwann cells - myelination & regrowth of central axons |
|
|
Term
| Differences of neuronal migration in the gut vs. the developing cortex |
|
Definition
In the gut the ENCCs have a very far distance to travel, compared to a relatively short one by the migrating cortical neuroblasts
In the gut, chemotaxic gradients (GDNF) drive the migration of the ENCCs, whereas in the cortex their migration is guided by the radial glial cells
In the gut, there are ligand/receptor interactions during migration; in the cortex, there is connexin/reelin/DCX association between the neuroblast & glial cell |
|
|
Term
| Comparison of GDNF receptors w/ NGF receptors |
|
Definition
High affinity = RET (for GDNF), TrkA (for NGF)
Low affinity = GRFa (for GDNF), p75 (for NGF) |
|
|
Term
| Characteristics of NGF knockout (-/-) mice from paper: |
|
Definition
Loss of sensory neurons from DRGs and sympathetic neurons
Ptosis & myotic pupils (from lack of sympathetics)
Decreased pain sensitivity (from lack of sympathetics)
Low survival rate
Normal development of basal forebrain cholinergic neurons |
|
|
Term
| Characteristics of TrkA knockouts from paper: |
|
Definition
Severe sympathetic and sensory neuropathies
Myotic pupils & ptosis
Numerous scabs appear on extremities with age (lack of pain)
Loss of neuronal populations in sympathetic and sensory ganglia (loss of neurons from TG, DRG, and sympathetic ganglia)
Decreased pain response |
|
|
Term
| Characteristics of p75 knockouts from paper: |
|
Definition
NORMAL sympathetic NS development
Some sensory neuron loss
Mice were completely fertile w/ a normal lifespan; normal internal organs
Sympathetic activity in salivary glands & eyelids was normal
Slight decrease in sensory innervation to skin (defect in heat sensitivity) |
|
|
Term
| In the paper that reported NogoA/B knockouts allowed for axonal regeneration, which of the criteria were met? |
|
Definition
Axon regenerates through injury site (into glial scar)
Axon follows a branching trajectory through environment
Axon has a distinct phenotype w/ collateral branches formed |
|
|
Term
|
Definition
| Chronic pain caused by lesion or disease of the somatosensory NS; pain persists after lesion has healed |
|
|
Term
| Chronic Regional Pain Syndrome (CRPS) |
|
Definition
| Chronic neuropathic pain disorder w/ burning pain, edema, motor weakness, skin colour & temperature changes |
|
|
Term
| What is labeled to identify postganglionic sympathetic fibers in the CRPS study? |
|
Definition
| Tyrosine hydroxylase - rate limiting enzyme of the pathway for NE synthesis in the sympathetic axons |
|
|
Term
| What are 2 different model systems in which NGF can be shown to be linked to pain |
|
Definition
Injury induced
NGF overexpression |
|
|
Term
| Injury Induced model of NGF/pain relationship |
|
Definition
In the normal mouse, a sciatic nerve lesion was shown to produce development of sympathetic baskets
Now in NGF-knockout - lesion was NOT followed by any sympathetic sprouting OR basket formation
Note: needed the injury to occur for the sympathetic baskets to form |
|
|
Term
| NGF overexpression and the NGF/pain relationship |
|
Definition
| In mice with NGF overexpression, DO NOT NEED injury for sympathetic baskets to form; see excessive S-S coupling (sprouting occurs independent of any injury) |
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