week 2 - long term potentiation Flashcards
Describe Morice et al. (2008) Learning and memory study
mice with a downsyndrome model vs wild type
Mice with downsyndrome have less synaptic plasticity
Where is the hippocampus?
In the medial temporal lobe
What is another reason why the hippocampus is widely studied in learning and memory
Because it is very easily accessed electrophysiologically
You can even remove it from the brain and it’ll stay alive for much longer than other areas
What is anterograde amnesia
Inability to form new memories
What is retrograde amnesia
Loss of old memories
Describe HM
A:
H.M. (Henry Molaison) had his medial temporal lobes, including the hippocampus, surgically removed to treat epilepsy. After surgery, he developed severe anterograde amnesia—he could not form new long-term memories, though his intelligence, short-term memory, and procedural memory remained intact.
His case provided strong evidence that the hippocampus is critical for forming new declarative (episodic and semantic) memories, but not for retrieving old ones or learning motor skills, showing that different types of memory rely on different brain systems.
What is an intepretation of the fact that most hippocampal damage leads to amnesia of recent memories or new memories
Memories might start off in the hippocampus and move elsewhere
Describe frankland and bontempi (2005) ‘s study on hippocampal lesions
Hippocampal lesions impair memory in rodents in a time dependent way
Memory created in rodents. , This was
either using classical contextual fear conditioning and social transmission of food preference
When hippocampus is lesioned soon after the memory is created the memory is lost
When hippocampus is lesioned after a month after the memory, the memory is generally not lost
This suggests that memories start in the hippocampus and move elsewhere.
This is consistent with the observation that H.M. has retrograde amnesia for events that occurred recently, but not in the more distant past.
What do human and animal studies reveal about the hippocampus and memory consolidation?
Damage to the medial temporal lobe in humans causes temporally graded retrograde amnesia, affecting recent but not remote memories, suggesting the hippocampus has a time-limited role in memory storage. This supports systems consolidation theory, where the hippocampus temporarily stores new memories, which are gradually transferred to distributed cortical networks through reactivation and synaptic changes.
Animal models allow controlled studies of lesion effects, confirming that recent memories are more vulnerable to hippocampal disruption. Imaging and lesion studies show that over time, memory traces shift to cortical areas, especially the prefrontal cortex, which helps integrate information and may inhibit hippocampal re-encoding during recall.
In contrast, multiple trace theory argues that the hippocampus is always needed for recalling episodic and spatial details, regardless of memory age. Overall, memory reactivation (during tasks or rest/sleep) is key to gradual remodelling of hippocampal–cortical circuits, stabilising long-term memory.
Describe Neves, Cooke and Bliss’s study into hippocampus circuitry
Most the input to the hippocampus comes into the dentate gyrus, flows to CA3 and flows to the hippocampus
The flow of information into the hippocampus in rodents is very simple
This is another reason why the hippocampus is a widely studied structure
How can you differentiate synaptic potentials and action potentials in the hippocampus in rodent hippocampal studies
Use a simple lamination (research more about this)
Because the hippocampus is simple, you can interpret what is synaptic vs. what is hippocampal, as well as being able to visualize the discrete fibre pathways
Describe a transverse hippocampal slice and why is this better in the hippocampus
You can look down at a slice of the rodent hippocampus and see the structure of the neural pathways
You can see what’s CA1, CA3 and you can stimulate different bits
This is better in the hippocampus cus in other brain areas the pathways cross over each other so you can’t isolate the different responses
What predictions would hebbian plasiticty theory generate / Criteria for a hebbian implementation of plasticity
Activity dependence - Modification of synsapses requires co-activity between pre and post synaptic neurons
input specifity- only inputs co-active with the post synaptic cell will undergo modification
Cooperativtiy - Multiple inputs are required to drive plasticity inducing post-synaptic depolarization
Associativity - Weak inputs that are unable to depolarize the cell sufficiently enough, will still undergo change if paired with strong depolarizing inputs
Longetivty - Phenomenons should be long-lasting if they are going to serve memory
Describe intracellular vs. extracellular recording and benefits
Intracellular - inside the neuron. EPSP’s can be measured
Benefits = low noise recording from individual neurons
Extracellular - Away from the neuron e.g eeg
How does the steepness of the EPSP slope correlate with synaptic strength?
The steeper the slope of the EPSP field recording, the stronger the population synapses
Describe Bliss and Lomo’s 1973 LTP study
(Q1- Activity dependence)
Looked in the dentate gyrus recieving input
Recorded from a population of excitatory neurons in a aneastetised rabbit
One neuron stimulated and one recorded in each hemisphere
One hemisphere recieved high frequency electrical stimulation, the other recieved low frequency control pulses
Only the hemisphere that has been stimulated undergone LTP, shown by A reduction in the latency of the population spike
LTP was measured as the field EPSP
This shows high frequency stimulation were required for increased synaptic strneght
This also shows that plasticity is activity dependent
How would you use intracellular recording to measure LTP (markram, 1997)
Q1 - Activity dependence
You can use spike timing dependent plastictiy
Stimulate with a single pulse the presynaptic input at the same time injecting the post synaptic neuron with current
If the presynaptic input is stimulate just before teh post synaptic cell we get a long term potentiation
The close the two stimulatoins are to being simultaneous, the stronger the LTP
Stimulating the post synaptic neuron first before the pre neuron leads to LTD - weakening of synapses
This shows timing of stimuli is important for LTP
This also shows activity is activity depndent
Q: What did Markram and Poo discover about spike timing-dependent plasticity (STDP), and how was it shown using intracellular recordings?
Using intracellular recordings, Markram and Poo showed that synaptic strength depends on the precise timing of pre- and post-synaptic firing, demonstrating spike timing-dependent plasticity (STDP).
Instead of using a high-frequency tetanus, they paired single synaptic stimuli with controlled post-synaptic firing at different time intervals. They found that:
If the pre-synaptic neuron fired just before the post-synaptic neuron (within ~50 ms), LTP occurred.
If the pre-synaptic neuron fired after the post-synaptic neuron, LTD occurred.
This confirmed Hebb’s idea that causal timing between neurons matters for plasticity, and revealed that STDP reflects a natural, timing-based form of Hebbian learning.
How would you demonstrate input specifity for synaptic plasticiy (beck et al, 2000)
(Q1 - Input plasticity)
tetanised vs. non tetanised input
In LTP experiments, only the synaptic pathway that receives tetanic stimulation shows a long-lasting increase in synaptic strength (black dots), while a separate, untetanized pathway onto the same neuron remains unchanged (white circles).
This shows input specificity, meaning only active synapses are strengthened, not all inputs to a neuron. This specificity confirms that LTP is a synapse-specific process, not a global change in the neuron, and serves as a control showing that observed changes are due to actual synaptic plasticity, not experimental artefacts like electrode drift.
This supports Hebb’s rule: “only synapses that contribute to post-synaptic activation are strengthened.”
What did Beck et al. (2000) show about input specificity in LTP?
Beck et al. (2000) used dual-pathway stimulation in hippocampal slices to show that LTP is input-specific. They stimulated two independent synaptic inputs onto the same post-synaptic neuron, delivering high-frequency tetanic stimulation to only one of them.
They found that only the tetanized pathway showed long-term potentiation, while the untetanized pathway remained unchanged, confirming that LTP only occurs at synapses that are active during induction.
This provided strong evidence for input specificity, a core property of Hebbian synaptic plasticity, and showed that synaptic changes are localised, not global across the neuron.
What is the two pathway preperation in the transverse hippocampal slice?
The two-pathway preparation involves stimulating two independent sets of synaptic inputs onto the same population of neurons (typically CA1 pyramidal cells) in a transverse hippocampal slice.
One pathway (e.g., via Schaffer collaterals) is given high-frequency tetanic stimulation to induce LTP, while the other is left unstimulated as a control.
This setup is used to demonstrate input specificity—showing that only the stimulated pathway exhibits synaptic strengthening, while the control pathway remains stable+
How would you demonstrate cooperativity and associativity in hebbian plasticity (Q1)
(McNaughton et al, 1978) Mcnaughton, 2003,
Barrioneuvo and brown, 1983
- Cooperativity – McNaughton et al., 1978 (revisited in McNaughton, 2003):
Preparation: Transverse hippocampal slice; Schaffer collateral inputs stimulated; recordings from CA1 pyramidal neurons.
Experiment: A single weak input (subthreshold stimulation) was unable to induce LTP on its own. However, when multiple weak inputs (from separate fibres) were stimulated simultaneously, they summated and induced LTP.
Conclusion: This showed that LTP induction requires coincident activity across multiple inputs to reach the depolarisation threshold necessary for NMDA receptor activation. This is cooperativity: “weak inputs must cooperate to induce lasting change.”
How would you demonstrate associvity in hebbian plasticity?
Associativity – Barrionuevo & Brown, 1983:
Preparation: Again, hippocampal slice; CA3–CA1 two-pathway stimulation to separate inputs onto the same CA1 neuron.
Experiment: One pathway received strong high-frequency stimulation (tetanus) to induce LTP. The second, weak pathway, was stimulated at a low frequency, which on its own would not induce LTP.
When the weak pathway was stimulated simultaneously with the strong pathway, LTP was also induced in the weak input.
Conclusion: This demonstrated associativity — a weak input becomes potentiated if it is co-active with a strong input, because the strong input depolarises the postsynaptic cell enough to relieve the Mg²⁺ block of NMDA receptors at the weak synapse, allowing Ca²⁺ influx and synaptic strengthening.
How would you measure longetivity in hebbian plasticity (Q1)
Abraham et al 2002
Induced LTP in dente gyrus of rat by many stimulations
LTP lasted for 100 days in a rat
LTP even lasted for one rat 360 days, this is half of the rats life
To demonstrate longevity, researchers induce LTP and then show that synaptic strengthening persists for days, weeks, or even months. This typically requires chronic in vivo recordings in awake, behaving animals.
Abraham et al. (2002):
Used chronically implanted electrodes in the dentate gyrus of awake rats.
Applied high-frequency stimulation (HFS) to the perforant path to induce LTP.
Recorded field excitatory postsynaptic potentials (fEPSPs) over many days to weeks after induction.
Found that LTP persisted for at least 1–2 weeks, showing that synaptic strengthening can be long-lasting and stable under naturalistic conditions.
Conclusion: This provides strong evidence that LTP is not just a short-term phenomenon, but can serve as a candidate mechanism for long-term memory storage, satisfying the longevity criterion of Hebbian plasticity.
