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38 Cards in this Set
- Front
- Back
3 major pathways in the hippocampus
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entorhinal cortex-> granual cells of dentate gyrus (perforant path.) granual cells-> pyramidal of CA3 (mossy fiber path) cA3-> ca1 pyramidal cells (schaeffer colateral path)
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Describe LTP in the mossy fiber path.
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NMDAr (post-syn) not required. Rep. stimulation of granule cells leads to incr. amplitude of epsp in pyramidal cells. due to ca+ influx_>ca/caM activate AC makes cAMP activates PKA ,activates NT
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Describe LTP in the schaeffer collateral pathway
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postsynaptic and presynaptic (though induced by postsynaptic). depolarization of postsyn by several axons required=cooperativity. this is because of dual gating of nmda-receptors. Ca influx sets of PKA cascade- regulatory unit + mapk into nucleus, induce gene transcription cepb and ubiquitin hydrolase
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pka pathway
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G protein activates Adenylyl cyclase via alpha subunit. AC produces cAMP from ATP, cAMP activates PKA, PKA phosporylates target proteins, including creb1,2 and Kchannel, Ltype Ca channel
critical for late LTP- no PKA or CREB eliminates late LTP |
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classical conditioning
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unconditioned (natural) wait 5s then conditioned stimulus. CS activates adenylyl cyclase and US activates serotonin receptrors coupled to ac. Third- retrograde signal back to presynaptic ell to increase NT release
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pkc pathway
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g protein
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phosphotase
phosphodiesterase ubiquitin hydrolase |
dephosphorylates protein
chews up cAMP chews up regulatory unit of PKA |
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molecular evidence of camkinase II regulation importance in memory/ use tetO/temporal example
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Tetracycline to temporally (not regionally) restrict gene expression. TetO promoter of bacteria is controlling a camKii -const. active gene. This transgenic mouse is crossed with a mouse expressing tTA(transcription factor) controlled by a camKII promoter. TeA binds tetO and promotes camKii-active gene which causes mouse to go screwy and have learning problems- too much unregulated camkinase. Doxycycline pulls tTA off tetO and no longer is camkii continually generated
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NMDA-r1 regional knockout- evidence of importance of nmda receptor in learning and memory
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Cre Recombinase only expressed through CamKII promoter in CA1 cells---CRE then is available to catalyze the recombination of the lox P recognition sites
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BMP suppression molecules
TGF-beta |
Chordin, noggin, follistatin bind BMP and block it from blocking neural route of ectodermal development
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medial->lateral:dorsoventral axis
sensory info___ motor info__ |
sensory,commisural=dorsal
motor, interneurons=ventral |
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anteroposterior axs
caudal portion:___ rostral portion:___ |
caudal portion: spinal cord
rostral portin: forebrain |
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SHH patterns the
while BMPs pattern |
ventral neural tube (motor)
dorsal tube (sensory) |
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shh expressed in floor plate and neural tube
bmp expressed in roof plate t or f? |
true!
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how does SHH work
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SHH binds to receptor PTC and relieves the repression on second TM protein (smoothed). SMO regulates protein kinases and activates a class of transcription factors (gli proteins) which enter the nucleus and induce expression of a number of genes.
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levels of SHH and the ventral differentiation
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Low concentrations of SHH induce ventral neural tube cells to become ventral interneurons while higher SHH concentrations induce differentiation of ventral neural tube cells into motor neurons and very high SHH levels induce cells to become floor plate cells.
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how does bmp work?
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BMPs activate transmembrane Ser-Thr kinases and phophorylates SMAD a transcription factor- goes to nucleus and interacts with other transcription factors
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how do dorsal and ventral patterning differ, mechanistically?
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Ventral patterning is regulated by different concentrations of SHH inducing different cell types.
In contrast, dorsal patterning involves several different members of the BMP family , each of which appears to induce a particular cell type. |
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name four types of ventral neurons that are induced by BMP
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motor neurons, ventral interneurons, dopaminergic, serotonergic
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lamellipodia
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motile end of axon/growth cone/ microtubules and actin mesh
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extracellular matrix cues
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lamella-11 different types in ECM and integrins on cone surface and bind cytoskeletal proteins in mesh- some specificity for type
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cell:cell interactions
Cadherins (Ca2+-requiring) and immunoglobulin-like adhesion molecules. |
Cadherins homophilic reactions
immunoglobulin: even more than 100 types, but bind to more types both link to cytoskeleton and trigger intracellular pathways |
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chemotaxis
netrins |
chemotaxis- gradient of chemicals
Intracellular factors can influence responses to netrins. For example, PKA activation leads to growth cone attraction to netrins; however, if PKA is inactive, repulsion towards netrins is seen instead. can also be a repellant |
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ephrins
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inhibitory signals and Eph kinases are receptor tyrosine kinases found on growth cones.
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Semaphorins
neuropilin and plexins |
Semaphorins (15 identified) such as collapsin-1 cause growth cone collapse and growth in the opposite direction.
receptors for semaphorins |
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neurotrophic factors
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facilitate growth and repair
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cytokines
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small proteins, that have specific effect, like hormones
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differentation of neural crest cells into neurons - environmental signals...
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BMP proteins signal the expression of a protein called mash-1 which is a transcription factor required for generation of central and peripheral neurons.
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differentation of neural crest cells into glia - environmental signals...
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GGF (glial growth factor) is expressed on the surfaces of autonomic neurons when they first differentiate. It inhibits neurogenesis on nearby neural crest cells, directing them to follow the glial cell differentiation pattern
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Differentiation of Glial cells
_maintains progenitor cells __ CREATES ASTROGLIA |
__PDGF__maintains progenitor cells
CNTF |
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NEURONS OF CORTEX are generated in the ___ zone
and are created in what order? |
ventricular
Cortical neurons are generated in an inside-first, outside-last order. |
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transplantation of cells depending on their cell cycle
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young cortical progenitor cells remain sensitive to time-dependent environmental signals that determine their fates. As they become postmitotic they become committed to a specific fate.
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an inadequate concnetration of neurotrophic factor secreted by target cells leads to
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apoptosis
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neurotrophic factors include bdnf,ngf,ctnf,interleukins, ec. and bind to 2 receptor types:- -
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p75NTR-binds all factors and tyrosine kinases- more specific to particular factor
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In the presence of neurotrophic factors and bound tyrosine kinase receptor...
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bcl2 supresses acaf which usually activates caspase (through cleavage)
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downstream effect of neurotrophin and cytokine binding
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neurotrophins and cytokines promote the dimerization of receptors and the activation of protien tyrosine kinases
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endogenous apoptosis program
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Sympathetic neurons in culture are maintained by NGF. Removal of NGF leads to apoptosis, but not if protein or RNA synthesis is blocked when NGF is removed. This suggests that neurotrophins antagonize an endogenous death program.
cell death genes- CED- are required for cell death |
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apaf is...
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evil
leads to cleavage and activation of caspases |