Possible short answer ones Flashcards
Cascade w/ LTP in CA1 of hippocampus
1) glutamate activates AMPA receptors
2) repeated glutamate excitation of AMPA depolarizes membrane
3) Mg2+ block on Ca2+ channels removed from NMDA
4) NMDA allows Ca2+ to enter in response to glutamate
5) entry of Ca2+ activates certain protein kinases
6) one is CaMKII, which activates AMPA receptors by - causing more to be produced and inserted, move nearby AMPA onto active site, increase conductance of Na+ and K+ ions in membrane bound AMPA
7) more AMPA built, dendritic branching increased
–> strong stimulation of postsynaptic one, retrograde messenger (diffusible gas) travels to presynaptic, alters function. lowers AP threshold, expansion of axons. (increase synaptic sensitivity to glutamate, synapse is strengthened)
–> activated protein kinases trigger protein synthesis
8) kinases activate CREB
9) CREB binds to cAMP responsive elements in DNA promoter regions
10) CREB changes transcription rate of genes
11) regulated genes produce proteins that affect synaptic function, contribute to LTP (AMPA, NMDA, etc)
–> MEK + ERK pathways increase CREB histone acetylation
Associative Learning in Fear Conditioning
CS and US converge on Lateral Amygdala (which receives input from thalamic and cortical areas). US relays strong stimulatory inputs and depolarizes them. CS simultaneously relays neutral stimuli, reinforces depolarization (usually a tone). Now, an aversive US like foot shock strongly depolarizes LA neurons. These neurons are more sensitive to future tones.
Depolarization causes Ca2+ influx through NMDAR’s, cause LA action potentialGlutamate opens a Ca2+ channel when postsynaptic cell is depolarized (by foot shock), any weak inputs such as tone that are simultaneously active allow local Ca2+ entry into dendrite. This causes new postsynaptic glutamate receptors to insert into postsynaptic site, potentiating the formerly weak synapse. Now CS alone is sufficient to cause EPSPs at sensory input synapse onto LA pyrimidal neurons in amygdala. i.e., associative learning occurs by strengthening synaptic linkages between the previously neutral inputs (tone) and the neurons of the amygdala.
Lower nutrition, imprinted genes, IGF2, increased risk for schizophrenia
Imprinted genes highly expressed not only in the placenta, but also in the brain, suggesting that the expression of these genes play an important role in brain development and behaviour. In mammals, Igf2 expression is regulated by DNA methylation of the Imprint Control Region (ICR). The ICR is not methylated on the maternal allele. This allows the CTCF protein to bind to the ICR and prevent enhancing factors from activating expression of the Igf2 gene because CTCF is blocking access. Conversely, the ICR is methylated on the paternal allele. This prevents the CTCF protein from binding to the ICR and allows the enhancing factors to activate expression of the Igf2 gene because CTCF is not blocking access. Low levels of dietary methyl donors during gestation results in reduced methylation of the ICR, increased CTCF binding and reduced Igf2 gene expression and function (similar to the maternal allele), which may contribute to restricted fetal growth. Schizophrenia is associated with an increase in Igf2 maternal allele expression in the neocortex, cortical undergrowth and enlarged ventricles.
HPA axis pathway
1) CRH neurons in hypothalamus release CRH at median eminence
2) CRH stimulates release of ACTH from cells in anterior pituitary
3) ACTH stimulates both synthesis and release of glucocorticoids from adrenal cortex
4) GC act, in part, to mobilize energy for the fight or flight response
5) GC also act to restrain the HPA axis by inhibiting hormone release at the level of the hypothalamus, pituitary, and higher brain regions
How Agouti Mice Work
Agouti mice wild types express agouti gene (A), resulting in banded-fur that brown. IAP is a retrotransponson that can insert into Agouti gene slightly upstream (Avy) and can effect transcription and phenotype. This has a cryptic promoter region called LTR. The degree that this LTR is methylated affects the resulting phenotype of mice. If it is highly methylated, the resulting mouse is pseudo-agouti (almost brown, banded fur) part time expression only in hair follicles. If it is lowly methylated, mouse is yellow, not banded fur, obese, unhealthy, ectopic expression (all the time). Most common phenotype = slightly mottled. More BPAs in moms diet = yellow. More methyl donors = pseudo-agouti. Methyl donors diet includes cofactors folic acid, vitamin B12, choline
chloride, and anhydrous betaine.
Anterior Pituitary Hormone Release
1) hypothalamic neurons synthesize releasing hormones
2) axons from these cells sonverge on median eminence
3) releasing hormones secreted into local blood vessels called hypophyseal portal system
4) releasing hormones carried to AP, then releases tropic hormones