Papers Flashcards
Optogenetic stimulation of a hippocampal engram activates fear memory recall (Liu)
Know, Gap, Hypothesis
Know: memory encode by neurons that can be tagged for identification, inactivation= reduced memory
Gap: Can you elicit behavioral output of specific memory by directly activating population of neurons active during learning?
Hypothesis: Reactivation neurons active during freezing = reduce memory expression
Optogenetic stimulation of a hippocampal engram activates fear memory recall (Liu)
Methods
Optogenetics- genetically engineer animals.
Labelled with ChR2
- Box (no fear)
- Shock box - label fear neurons
- Animal back in original box, shine light it becomes scarred
Optogenetic stimulation of a hippocampal engram activates fear memory recall (Liu)
IV, DV
IV:
Fear + ChR2 expression
No Fear + ChR2 expression
Fear + Florescent Yellow Protein
DV: Freezing behavior
Optogenetic stimulation of a hippocampal engram activates fear memory recall (Liu)
Results and Conclusions
optogenetic reactivation of hippocampal neurons activated during fear sufficient to induce freezing behavior.
Increase only upon light stimulation, only in Fear + ChR2
Activation of that engram causes animal to freeze in context it wasn’t afraid of
Rapid decrease in depression symptoms with N-methyl in ECT resistant… (Ibrahim)
Know, Gap, Hypothesis
Know: Ketamine improves symptoms in treatment resistant, acts rapidly
Gap: Equally effective in those who have had ETC?
Hypothesis: Is it as effect in patients whose depression doesn’t respond?
Rapid decrease in depression symptoms with N-methyl in ECT resistant… (Ibrahim)
Methods, IV, DV
- Everyone gets 0.5 mg/kg ketamine
- MADRS and CADSS 60 minutes before and in intervals afterwards
IV: did not respond to ETC vs. did not receive ETC
DV: how they responded on MADRS and CADSS
Rapid decrease in depression symptoms with N-methyl in ECT resistant… (Ibrahim)
Results/Conclusions
- Both groups decrease depressive symptoms
- Group without ECT previously had greater symptom decrease that group that did have ETC
Appears to improve symptoms.
Confound: Hospitalization (future direction)
FGF2 augmentation early in life alters hippocampal development… anxiety phenotype (TURNER)
Known, Gap, Methods
Known: Mood disorders have altered FGF2, disrupted in anxiety, involved with connectivity. Decrease in anxiety
Gap: Are these a cause or consequence?
Hypothesis: FGF2 given a day after birth has long-lasting effects on hippocampal development and emotionality
FGF2 augmentation early in life alters hippocampal development… anxiety phenotype (TURNER)
Methods
- Breed high/low responders
- FGF2 injections
- Markers in hippocampus (see below)
Used Laser capture microscopy and microarray analysis (reveal expressed genes)
Stained with…
BrdU- newly synthesized DNA
KI67- nuclear protein associated with proliferation
FGF2 augmentation early in life alters hippocampal development… anxiety phenotype (TURNER)
Results
FGF2 increased proliferation in subgranular zone of dentate gyrus and cell survival in granule cell layer
BrdU and KI67 both increase in FGF2 rats
- Behavioral: more time in light box/open arms, decrease latency to enter
- Genetic: increases Ntrk3 and BCL212 expression, up regulated genes for cell survival, down regulated anxiety genes
- Neural: FGF2 increase cell survival in dentate gyrus 3 weeks later/ cell proliferation
FGF2 augmentation early in life alters hippocampal development… anxiety phenotype (TURNER)
Conclusions
FGF2 involved in develop of hippocampus and modulation of anxiety behavior.
Potential downstream targets for anxiety
SWS during daytime nap…interference and LTP (Alger)
Known, Gap, Hypothesis
Known: sleep facilitates processing of newly acquired declarative info. Hippocampal activation during sleep contingent on acquisition level during training
Gap: what type/length of sleep needed for declarative memory?
Hypothesis: SWS obtained to consolidate declarative memory
SWS during daytime nap…interference and LTP (Alger)
Methods, IV, DV
- Bimodal pairs (36 total)
- Sleep - 9 electrodes
- Retested
- Interference
- Retested
- 1 week later- another SSS, ask about 10 learned items
IV: 10 min, 60 min, wake
DV: % Correct each test
SWS during daytime nap…interference and LTP (Alger)
Results/Conclusions
Both naps groups better at short term retention
10 min effects temporary, interference blocks it
SWS activity facilitates consolation of learning bimodal pairs
ACTIVE ROLE OF SLEEP
Synaptic Scaling Across Sleep/Wake Cycle (De Vivo)
Know, Gap
Know:
- Correlations between ASI/spine size, etc.
- Changes in synaptic strength primary mechanisms for learning/memory
- Potentiation/depression must balance to avoid saturation/obliteration of neural signals
Gap: Does synaptic strength/weakening happen throughout learning when awake or during wake/sleep
Depression- sleep
Potentiation- wake
