Brain network mechanisms and Behaviour Flashcards
Hippocampus is important for episodic and spatial memory. How? What are the network mechanisms that underlie memory?
- Hippocampus contains ‘place cells’
- ‘Phase precession’ and ‘theta sequences. Hippocampal theta oscillations beautifully organize the activity of place cells.
- This beautiful organization is ‘replayed’ after learning to consolidate memories.
What are place fields?
- Hippocampus creates place fields to map our environment.
- Place fields are specific areas in an environment where place cells (neurons in the hippocampus) fire when you are in that location.
- Each place cell corresponds to a specific part of the environment- together, they create a neural map.
- Temporal organization: place cells fire in a sequence that reflects the order in which you move through a space - this helps organize spatial and episodic memories over time.
Patient HM
- HM had severe epilepsy -> doctors removed his hippocampus at age 27.
- Could not form new memories from age 27–84 (anterograde amnesia).
- He could recall old memories formed before surgery because these were stored in the cortex.
- The hippocampus is not important for long-term storage — it’s important for creating new memories.
- After memories are made, they are transferred to the cortex for storage.
- HM’s cortex was intact, so he retained previously stored knowledge (semantic memory).
What type of memories does the hippocampus help create?
- Declarative memories (things you can state).
- Example; knowing the capital of France is Paris.
- Hippocampus acquires episodic memories (events) quickly -> overtime, these memories are transferred to the cortex for LT storage.
(semantic knowledge (facts) is stored in the cortex after being processed by the hippocampus)
What test was used for animal studies to study Hippocampal Lesions?
-> Water Maze test (used to study spatial memory in rats).
- Rat placed in a pool with a hidden platform.
- Over repeated trials, rat remembers the location and swims directly to the platform (spatial learning).
Hippocampal lesion effects:
1. Remove ventral hippocampus → memory intact → rat finds platform.
2. Remove dorsal hippocampus → memory disrupted → rat swims randomly.
3. Remove entire hippocampus → complete loss of memory → rat swims randomly.
What results were obtained from Context Fear Conditioning Test?
- animal placed in a chamber -> receives a mild shock -> forms a memory of the environment.
- test: brings animal back into the same chamber the next day.
- If memory is intact -> animal shows freezing behaviour (fear response).
Hippocampal lesion timing:
- Remove hippocampus immediately after shock → no memory of the context → no freezing.
- Remove hippocampus days later → memory already transferred to cortex → animal still freezes.
- X-axis in data = number of days before lesion → shows how memory strength changes over time.
Who discovered Place Cells?
- John O’ Keefe
- Used extracellular recordings in awake, behaving rodents.
- Four microwires twisted into a bundle.
- Different neurons will have different amplitudes on the four wires.
- Implanted microelectrodes into hippocampus to measure neuron activity.
- Raw data = spikes from many neurons (use high-pass filtering to isolate action potentials from individual neurons) - local field potential is primarily at low frequencies, spikes are at higher frequencies, so use a high pass filter - around 800hz cutoff.
- Place cells fire when the animal is in a specific location.
- Explicit memory creation during sleep demonstrates a causal role of place cells in navigation.
What part of stimulation of the brain is highly reward for rats?
- Place cells are recorded from the hippocampus in rats to study spatial memory.
- Stimulation of MFB (Medial Forebrain Bundle) is highly rewarding for rats (even more rewarding than food or drugs like cocaine)
- This stimulation makes rats willing to do almost anything to receive the reward.
Pairing place cell firing with rewards:
- By pairing the activation of place cells with a rewarding stimulus, rats learn to associate certain locations with rewards.
- After this association, the rat will return to the same location to receive the same reward.
What is the connection between sleep and a rat receiving a reward?
- When the rat is asleep, the place cell that was associated with the reward spontaneously activates.
- The rat is then stimulated with the reward while it sleeps.
- When the rat wakes up and returns to the environment, it immediately runs to the location of the place field, showing memory of the location.
What is the affect of CPP drug?
- NMDA receptor blockade (using CPP drug) abolishes long-term stability of place cells.
- Long-term potentiation (LTP) is not required to generate place fields, but it is needed to remember them over the long term.
- Without LTP, place cells will remap and change their tuning properties the next day.
What are the input pathways to the hippocampus? How did they figure out where place cells were being generated?
- Entorhinal Cortex (EC): Pathway through which information enters the hippocampus.
- To main pathways to CA1 (the area of the hippocampus where place cells are record)
- Direct input to CA1 from EC.
- Indirect input via DG (Dentate Gyrus) -> CA3 -> CA1.
DG -> CA3: A feedback loop where CA3 projects to itself.
- Lesioning the indirect pathway (DG → CA3 → CA1) did not disrupt place fields.
- This suggests that place cells are not generated from the DG, and place fields still appear in CA1.
What is the role of the Entorhinal Cortex (EC)?
- Divided into two regions.
- Lateral EC (LEC): No significant impact on spatial memory (no effect on water maze performance).
- Medial EC (MEC): Important for spatial processing and place cell generation.
Therefore,
MEC lesions significantly impact spatial memory and the formation of place cells.
Where were grid cells discovered?
- MEC
- These cells have multiple small fields organized in equilateral triangles.
- In larger environments, the grid pattern forms a hexagonal grid.
- Grid cells are involved in spatial navigation and self-motion processing.
- Grid cells persist in complete darkness, suggesting they rely on self-motion cues to generate spatial maps of the environment.
- Grid cells help integrate self-motion cues (tracking movement in all directions) to map out environments.
- Grid cells form immediately when a rat enters a new environment, helping it to build a spatial map.
What is the evidence for Grid Cells in Humans?
- Studies using fMRI have shown that grid cells are involved in spatial memory and navigation in humans.
- In Alzheimer’s disease (AZ), patients often get lost due to disruptions in grid and place cells.
- fMRI studies have shown impaired grid cell activity in AZ patients, further linking grid cells to spatial memory.
Where are the neurons that are encoding location?
Medial Temporal Lobe
- Hippocampal theta oscillations occur in the brain, reflecting highly precise neural firing.
- Seen in mammals.
- Rhythmic oscillation that tracks neural spikes.
- As long as animal is not asleep, it remains in theta state.
- Theta oscillations can be plotted alongside individual neuron spikes, and they follow each other rhythmically.
What is Theta Phase Precession?
- Phase Precession refers to how the spiking of neurons changes within the theta rhythm.
- When a neuron enters its place field, its spiking begins at the peak of the theta oscillation.
- The neuron spikes slightly earlier with each burst, gradually shifting until it spikes at the trough of the theta wave as the animal moves through the place field.
- This is called phase precession — a shift in timing that helps encode the animal’s position as it moves through the environment.
Why is Phase Precession Important?
(1) Mouse experiment setup:
- The mouse head is fixed on a running wheel for precise experiments.
- The mouse runs on a ball, navigating through a virtual reality (VR) environment.
- Intracellular recordings measure the neuron activity while the mouse is in the VR environment.
(2) Findings:
- Before entering the place field, the neuron’s membrane potential oscillates at theta frequency.
- When the mouse enters the place field, the theta frequency speeds up.
- Phase precession occurs because the neuron’s oscillation becomes faster than the external theta oscillation recorded from outside the neuron.
Why Study Phase Precession?
- As the animal moves through the environment, it doesn’t just experience one place field. Instead:
–> Thousands of cells each have their own place fields.
–> Each neuron is phase precessing in a slightly different way.
–> The sequence of activity within each theta cycle is preserved (e.g., green, magenta, yellow), representing the animal’s movement in space. - The brain compresses information about past and future locations within each small chunk of time (about 125ms per theta cycle).
- The sequence of place fields helps to encode both past and future locations efficiently.
Theta vs Sharp Wave Ripples
- When animals stop moving:
- The theta oscillations stop.
- Sharp wave ripples take over during resting or SWS (slow-wave sleep). - During sharp wave ripples
- Pyramidal cells (from hippocampus) fire in clusters.
- These clusters are synchronized around sharp wave ripples, which may play a role in memory consolidation.
- Sharp-wave ripple events are conserved across species.
- They occur during slow wave sleep and resting.
- Place cells reactivate during sharpwave ripples.
Hippocampal theta oscillations
- 6-10 Hz oscillations in local field potential in hippocampus and related structures.
- Observed during exploratory and attentive behaviour.
- Seen in rats, mice, gerbils, rabbits, bats, pigeons, monkeys and humans.
- Reflects highly precise spike timing throughout the hippocampal structures.
What is phase precession a result of? What is the consequence of it?
- The neuron oscillating faster than the extracellularly recorded theta oscillation.
- Temporally structured cell assemblies.
- Representation of past, current, future, locations.
What were the results when recording of place cell activity in a linear track?
- theta oscillations when animal is running.
- sharp wave ripples when animal is resting.
(before running, during rest, sharp wave ripples activate all the place fields the animal will soon pass through). - after the run, when the animal reaches the end, the same place fields are activated again.
- replay: The place cells fire in the same order as they did during the run.
- reverse replay: At the end of the run, the place cells fire in the reverse order of the original run.
How can you use decoding analysis technique to interpret the data from from linear mouse track?
- Use the spiking patterns from the place cells to train a model.
- Test the model on a different dataset.
- The model will try to guess the animal’s position from the place cell activity.
- If the model is working well → The guess (triangle) will match the animal’s actual position when it is moving and firing place cells.
- When the animal is resting (during sharp wave ripples):
- The model can still guess the animal’s position based on the firing sequence.
- This shows that the hippocampus is replaying previous trajectories the animal experienced on the track.
Does ‘Replay and Reserve’ Replay in Humans?
yes
Hippocampal sharp wave ripples:
Trigger activity throughout the cortex.
Blocking sharp wave ripples -> impaired memory consolidation.
An experiment showed that when replay is disrupted, memory formation is weakened.
