Learning and Memory Flashcards
Give the definition of learning
An adaptive change in behaviour from experience
Define memory
The retention of learning
Describe the mechanism of learning
Fill in later
Name the two types of memory and their availability, formation, short term storage, and long term storage attributes
Fill in later
Disorders of declarative memory stem from…….
Give a case study which supports this
…. damage to the medial temporal lobe
Case Study: HM - had epilepsy from 10 y/o. Had a bilateral resection of MTL which controlled epilepsy. HM could recall early memories and IQ of 112 was unchanged but he had severe anterograde amnesia
Give three features of declarative memory and evidence for each
1: DM is distributed in various cortical sites
Evidence: Karl Lashley (1920’s) - Rats with brain lesions given maze tasks. Showed location of lesion wasn’t significant, only extent of lesion and task difficulty - ‘MASS ACTION PRINCIPLE’
2: Hippocampus is the organisational centre for DM
Evidence: Hippocampal inputs (afferents) match outputs (efferents) - place where recall happens as well as learning
3: Different regions of MTL are responsible for different aspects of DM
Evidence: Daselaar et al (2006) - subjects given 120 english and 80 non-words (2 s/item), after 30 mins they were tested on recall and familiarity and brain activity measured. Recollection - Highest activity in posterior hippocampus; Familiarity - Highest activity in posterior parahippocampal cortex; Novelty - Highest activity in anterior hippocampus and rhinal cortex
Epstein and Kanwisher (1998) - Post Para Hippocampal place (PPA). Subjects were shown pictures and their brain activity measured. PPA is strongly activated by spatial information, but not objects or faces. People with damaged PPA have trouble navigating novel environments
Describe the basic mechanism of non-declarative memory
Input enters cerebellum - striatum (doing part of brain) - motor cortex - action
When two signals reach the cerebellum at the same time, the become associated
e.g. Tone + Airpuff = Eye blink -> Tone = Eye blink
Describe how MRI and fMRI works
MRI - Uses strong magnetic field to align protons. Burst of radio waves flip protons out of alignment. When protons flip back, the energy change is recorded
fMRI - measures areas with higher levels of oxygenated blood (activity) - Not infallible: people have taken readings from dead salmon
Give a brief summary of declarative memory encoding
- Object information is represented by the perirhinal cortex (relational information comes from neo cortex)
- Contextual information processed by the para hippocampal cortex
- The two types of info are integrated by the hippocampus
Describe Hebb’s postulate and Hebb’s learning rules
The synaptic connection between cells A and B is affected (strengthened) because A keeps firing B
Learning Rules:
Correlated pre- and post-synaptic activity causes synaptic strengthening/stabilisation (A + B firing)
Uncorrelated pre- and post- synaptic activity causes synapse weakening/elimination (A firing, B not)
“CELLS THAT FIRE TOGETHER, WIRE TOGETHER”
Define Synaptic Potential
Depolarising/hyper-polarising potential die to activation of neurotransmitter receptors
Define EPSP
Excitatory post synaptic potential - measure of synaptic strength at excitatory synapse
Describe a study which shows the associativity of LTP
Nicoll et al (1998)
Tetanic stimulation of a weak input does not produce a high enough EPSP to fire the post-synaptic cell (No LTP occurs)
Tetanic stimulation of a strong input causes the post-synaptic cell to fire (resulting in LTP)
Tetanic stimulation of strong and weak inputs at the same time causes firing of the post synaptic cells and causes LTP in both strong and weak pathways
Example: Pavlovs dogs -
Strong signal = Food
Weak signal = Bell
State how LTD occurs
Generated by repetitive low frequency stimulation of input - results in persistently reduced synapse strength
Describe Bliss and Lomo’s 1973 study and it’s findings
To do later
Give the mechanisms of pre-synaptic plasticity
Probability of release
Filling of vesicle
Transmitter concentration in synaptic cleft
Describe the mechanism of retrograde messages in terms of synaptic plasticity
Signals that can diffuse out of the post synaptic terminal and influence activity of the pre-synaptic terminal
e.g. NO, CO, neutrophins
Give the mechanisms of post-synaptic plasticity
Insertion of new receptors
Gating of existing receptors
Describe how Ca2+ is involved in short term plasticity
Paired paired pulse facilitation
Seen when two pulses are delivered in very quick succession (less than half a second apart). Pulse B results in higher excitation
Caused by residual Ca2+ in cell from pulse A. excitation is Ca2+ dependant
Briefly describe the synaptic vesicle cycle
Filling, Docking -ATP-> Priming -Ca2+-> Exocytosis and fusion -Ca2+-> Endocytosis
Describe and give examples of four types of protein required for the synaptic vesicle cycle
Glutamate Transporters - required for vesicle content (KO = decrease in neurotransmission)
Synapsins - mobilisation of synaptic vesicles
Rab3/RIM1 alpha - Docking and priming of vesicles
SNAREs, munc18 - Synaptic vesicle fusion
Name the protein required for synaptic vesicle mobilisation and state how they are required.
Synapsins
Vesicles mobilised by synapsins which bind them to the actin cytoskeleton
Describe the process of vesicle docking and name the proteins involved
Rab3 (“Passport of vesicle trafficking”) which is a GTPase
GDP bound form is inactive. GTP bound form binds to vesicle and binds an effector (RIM1) on the membrane. This allows docking.
Once exocytosis occurs, Rab3 is hydrolysed and released from the vesicle
Explain the process of synaptic vesicle fusion
Uses SNARE proteins (Synaptobrevin - vesicle associated, Syntaxin - embedded in membrane, SNAP-25 - present on membrane, Synaptotagmin - vesicle associated)
Synaptobrevin, Syntaxin and SNAP-25 form coiled coil and energy from ‘zippering’ brings membranes together
Synaptotagmin mediated Ca2+ dependant process
Vesicle tethered by Rab3 which brings the vesicle into membrance, munc18 is removed from membrane SNARE complex (priming). Full SNARE complex forms on membrane - zippering allowed once Ca2+ has bound to synaptotagmin. Fusion occurs, NT released, NSF and SNAP disassemble (ATP dependant)
Describe studies to show the critical nature of synaptotagmin
Critical for Ca2+ dependence of vesicle fusion.
Difficult to prove. KO mouse dies before birth (mutants in Ca2+ chelating Amino acids are lethal)
Mutant in R233 amino acid in Ca2+ binding site (R233Q) reduces affinity of Ca2+ to synaptotagmin and also Ca2+ affinity of NT release
Describe the two types of neurotransmitter receptor
Ionotropic (Ligand gated ion channels) - NT binds, conformational change in channel helices, ions flow in. ‘Fast’ receptor
Metabotropic (G-protein coupled) - NT binds, G protein a subunit binds to effector protein which send intracellular messages to ion channel. ‘Slow’ but potentially longer lasting
Give properties of NMDA and AMPA receptors
NMDA and AMPA: Tetrameric, homodimers, glutamate binds in M3, M4 loop, NMDA/AMPA looks similar glutamate (only binds its respective receptor)
NMDA: Gates Ca2+ and Na+, D-AP5 is a blocker, in the absence of glycine the receptor does not function, Mg2+ block in the ion pore (voltage dependant, depolarisation removes Mg2+)
AMPA: Gates primarily Na+ and sometimes Ca2+, NBQX is a blocker
Describe the Yeast 2 Hybrid Assay
Used to study protein-protein interactions
Bait is protein of choice, go ‘fishing’ in solution of protein (i.e. mushed up brain) and pull out what binds to bait
In post-synaptic setting - Get a transcription factor, split it in half, attach bait to one half and express the other half at the end of genes expressed in yeast, If they come together, transcription of the gene will occur
Give an advantage and disadvantage of using aplysia as a model organism
Adv: Neurons arranged in ganglia, cell bodies are large
Dis: Relies on v. simple learning paradigms (i.e. tail shock, touching siphon)
Give the definition of habituation
Reduction of psychological or behavioural response occuring when a specific stimulus occurs repeatedly
Give the definition of sensitisation
The process of becoming susceptible to a given stimulus that previously had no effect or significance
Describe habituation in Aplysia
Touch siphon -> Gill withdrawal
Gill withdrawal weaker after repeated stimulation of siphon
Describe sensitisation in Aplysia and give methods for long and short term sensistisation
Pairs electrical stimulation of tail with light touch of siphon
Light touch of siphon -> Strong gill withdrawal
Short term: Single tail shock and siphon touch lasts a few hours (post translational modification)
Long term: Multiple trains of shocks ( 4 trains of 10 for four days) cause sensitisation to last days (requires structural changes at synapse - protein synthesis)
Describe how Habituation and sensitisation affects the neural circuitry of Aplysia
Habituation: Glutamate release by sensory neuron decreases - responsible for decrease in behavioural response
Sensitisation: Serotonin is released from inter-neuron on to sensory neuron (skin) and enhances the action of glutamate (via PKA) (and skin sensory neuron)
Describe structural changes seen at Aplysia synapses after sensitisation
Synaptic bouton number increases/decreases during sensitisation/habituation (Long term only)
Habituation decreases
Sensitisation increases
This requires gene expression and protein synthesis
Describe the effect of PKA on sensitisation
When serotonin is released from inter-neurons to to sensory neurons, PKA is activated. PKA activity increases NT release in sensory neuron
PKA is required for short and long term sensitisation
Describe fear conditioning in rodents
Classical: Sound paired with aversive foot shock. Association of sound with shock - fear of sound.
Extinction of fear requires exposure to sound with no shock
Operant: Skinner box - reinforcement positive (food) /negative (electric shock). Rewarded behaviour is repeated
Describe spatial learning in rodents
Morris Water Maze - Hidden platform under water, rat must find platform
- After 10 trials, rat goes straight to platform (WT)
- Rats with hippocampal lesions do not improve (PPA damage)
Latency, platform crossings and time spent in quadrants is measured
Rodents use surrounding areas to orientate themselves (i.e. chairs, clocks). Move objects and they struggle to find platform
Mutants in CREB struggle at improving with one trial per day, 4 trials per day see improvement similar to wild type
Briefly summarise short term plasticity
Dependant on Post-synaptic activation of AMPA receptors and NMDA receptors
Ca2+ influs through AMPAR starts depolarisation. This removes the Mg2+ block in NMDAR. Ca2+ modulated signalling pathways (Calmodulin Kinase II and Proetin Kinase C) are initiated and substrate phosphorylation occurs, leading to the insertion of additional AMPA receptors
For long term plasticity to persist beyond 2 hrs…
…synaptic signalling pathways initiated at the synapse (kinases) are required effect changes in the nucleus
Give evidence that long term LTP requires gene transcription
in CA3:CA1 pathway, give multiple trains of 100Hz. Control shows normal long term LTP, Add actinomycin D (transcription inhibitor) or anisomycin (protein synthesis inhibitor) before tetanic stimulus and early LTP is demonstrated but late LTP is blocked
Apply inhibitors after stimulus and it has no effect suggesting that gene expression changes are induced early
Give evidence that long term facilitation requires gene transcription
Simulation of pairing tail shock with gill withdrawal in Aplysia.
Apply serotonin to cell (in bath) for 5 mins. Look at EPSP immediately after and 24 hrs later (response similar each time) . 5 doses of 5 mins spaced 15 mins apart of serotonin shows long term faciliation of the neuron. 24hrs later, there is a huge enhancement of the response
(Application of actinomysin D or anisomycin at time of serotonin application blocks LTF)
Name some Immediate early genes (IEGs) and give the role
Regulatory genes (encode for TFs): c-fos, zif268, c-jun
Effector IEGs:
- Arc - protein involved in exocytosis of AMPA receptor
- BDNF - Growth factor that alows synapse growth and can potentiate NT release
- Homer1a - Scaffolding protein that links proteins in post synaptic density
ALL ARE TARGETS OF CREB
Describe the action or Arc as an effector IEG
Associate with Endophilin and Dynemin - mediates AMPA receptor endocytosis
Interacts with Wave3 (involved in actin remodelling) - possibly involved in structural plasticity of LTP
