Neural activity and memory engrams
Chemogenetics v.s Optogenetics
Seq'ing a Cure
Parkinson disease
???
100
An animal is startled by a tone, which causes them to increase their blood pressure and freeze. The tone (conditioned stimulus) is then paired with an unconditioned stimulus, which is a shock. What will happen if the conditioned stimulus of the tone is played without being shocked?
The animals blood pressure will increase and the animal will freeze
100
Which of the following are TRUE about memory?
A. reactivating a memory can make it sensitive to change.
B. the emotional state at the time of memory retrieval can alter reconsolidation of the memory
C. memories can be unreliable
D. memories can be tagged in rodent models with effector proteins like opsins and DREADDs for later manipulation in vivo
E. all of these
E
100
Indication of ALS can be found through staining of muscle biopsy for which protein?
What is TDP-43
100
What is the main type of neuron that degenerates in Parkinson's Disease
Dopamine neurons (substania nigra)
(other cell types degenerate as well like NE, 5HT)
100
What is Dr. Robertsons favorite Neurotransmitter?
What is NE?
200
The chemogenetic tool _____________ is activated by CNO causing neuronal inhibition through hyperpolarization. To facilitate hyperpolarization ________ activates its ________ which dissociates and opens a K+ channel.
hM4Di
hM4Di
G Protein
200
The Smith lab is trying to perform an experiment to stimulate a memory engram. Jack says that the priority of the lab should be longer-term neuromodulation, while Jill says that for cost reasons, the priority of the lab should be designing an experiment does not require any specialized equipment. What should each lab advocate for?
Both chemogenetics
200
RNA sequencing can...
a) enable discovery of novel diagnostic biomarkers
b) enable quantification of low abundance transcripts
c) quantify expression of known & novel RNA transcripts
d) all of these
All of these!!
200
This region of the brain could be used as a target for grafts of induced pluripotent stem cells in parkinson's patients
What is the striatum
200
the cFos promoter and _____ system was used to control DREADD or ChR2 expression in memory engrams in our two papers about fear learning.
what is tTA/doxycycline system
300
Which of the following are true about the approach pictured above.
a. A viral vector expressing hM4Di is injected into the dentate gyrus to enable spatial control over which memory engrams cells are labeled.
b. a transgenic mouse that expresses ChR2-EYFP directly downstream of c-fos enables temporal control over when a memory engram is labeled
c. Being ON-dox prevents ChR2 expression in experimental animals
d. all of these are true
C
300
Opsins were created
a. Using a protein engineering approach
b. By a lab here at UNC
c. Using channels from algae
d. Using mutated muscarinic receptors
e. A, B, and D
C
300
Which disease is correctly linked with is its key characteristics, symptoms and/or pathology? Select all that apply
A. Multiple Sclerosis: demyelination of neurons causes weakness, numbness, cognitive changes, etc.
B. Parkinson's disease: inability/slowness to initiate voluntary movement due to loss of substantia nigra dopamine neurons
C. spinal muscular atrophy: neurodegenerative disease that causes loss of upper and lower motor neurons only in adulthood
D. Amyotrophic Lateral sclerosis: number one cause of genetic infant mortality due to loss of dopamine neurons
A and B
300
The percentage of individuals with a mutation that will get Parkinson's Disease is low and variable, this is the concept...
reduced penetrance
300
Rett syndrome is an example of a “goldilocks” disease in gene therapy. What does this mean?
expression of the gene must be tightly controlled because too much MECP2 protein is as detrimental as too little
400
Activation of a few connected auditory sensory neurons related to a stimulus pairing can trigger a spread of neuronal activation to an entire __________
memory trace or memory engram
400
In Panel C, CNO-induced stimulation of neurons activated in context A _____ memory retrieval in context B in hM3Dq animals
enhances
400
What kind of high-throughput approach was used to identify the molecular subtypes of ALS depicted in the top panel of the figure? Which subtype of ALS is associated with significantly shorter survival duration?
RNA sequencing (transcriptomics)
ALS-Glia subtype (gold)
400
Provide evidence for the environmental etiology of PD...
A. Incidence of PD is greater in individuals exposed to certain environmental factors such as pesticides and traumatic brain injury
B. Incidence is lower in smoker and caffeine users
C. Incidence is higher in people who live in rural areas or near wells
D. There are some clusters linked to the influenza epidemic
400
Define each component of the zolgensma gene therapy: Avexis’s scAAV9.CB.hSMN
sc = self complementary design of the vector gives big gene expression in mammalian cells
AAV9 = adeno associated virus serotype 9 that crosses the blood brain barrier
CB = hybrid cytomegalovirus enhancer and chicken beta-actin promoter (drives rapid, high levels of expression in mammalian cells)
hSMN = human Survival Motor Neuron gene
500
What does Panel "i" provide evidence for?
When ChR2 expressing neurons are stimulated to fire action potentials with blue light, immediate early gene (cfos) expression is increased inside the cell.
This is evidence that ChR2 is indeed enabling experimenters to activate neurons with blue light.
500
In panel B middle graph, Arch T light induced silencing of prefrontal long-term fear memory engram neurons significantly _______ fear recall
decreases
500
Select the correct interpretation of the data
a. KO of Rab7 protects against PR toxicity
b. Treatment of primary neuron cultures with DPR increases cytotoxicity in a dose-dependent manner
c. delivery of DPRs to primary neuron cultures via lentiviral vector reduces the levels of cytotoxity
d DPR treatment of primary neuron cultures enhances the expression of LDH and NeuN+ cells
b. Treatment of primary neuron cultures with DPR increases cytotoxicity in a dose-dependent manner
500
The monkey PD scores for the PD group (red triangles) decreases over time after transplantation. What does this mean for the monkey's behavior?
The monkeys in the PD group are showing LESS severe parkinsonian symptoms over time after the graft is implanted.
(the graft comes from iPSC from PD patients)
500
Why did Kikuchi et al. stain for Ki-67 when conducting their induced pluripotent stem cell experiments (shown below)?
No Ki-67 staining is observed in grafted cells, indicative of no malignancy or tumor formation in the graft