Hippocampus Flashcards
where was patient HM’s lesion that caused his epilepsy?
behind frontal lobe
what type of memory was affected in HM?
declarative / episodic memories
what is declarative/explicit memory?
events (episodic memory) and facts (semantic memory)
what is nondeclarative/implicit memory?
procedural memory, perceptual representation, classical conditioning, nonassociative learning
what does CA stand for?
Cornu amonis
what contains the hippocampal formation?
CA1-3, dentate gyrus, entorhinal cortex, subiculum, pre and Para-subiculum
what is the human hippocampus volume compared to rat and monkey?
human hippo volume is 100x bigger than a rat’s and 10x bigger than a monkey’s
what type of cells are in the dentate gyrus and CA1/3 and how many?
- DG = 1.2 million GRANULE cells, 4000 basket cells, 32 000 hilar interneurons
- CA3/1 = 330 000 to 420 000 PYRAMIDAL cells, many interneurons too
what layers of the entorhinal cortex project where?
- layer II = DG and CA3
- layer III = CA1 and subiculum
what layer of EC receives input from what region of the hippo?
EC layer 5 receives from CA1 and subiculum
what synapse is one of the largest and most powerful in the brain?
the mossy fiber synapse!
what type of connections are between DG and CA3 and CA1?
DG -> mossy fibers -> CA3 -> schaffer collaterals -> CA1
what are the 3 inputs going to CA3? how many of each?
- 50-80 mossy fibers from DG
- 3 500 perforant pathway from EC layer 2
- 12 000 recurrent collaterals from CA3
the recurrent collaterals in CA3 are separated between what?
they either go to basilar dendrites (8000) or to apical dendrites (4000)
where does CA1 get input from?
- schaffer collaterals from CA3
- from EC layer 3
where does the medial vs lateral EC projections separate and where do they each go to?
medial EC layer 3 go to proximal CA1, lateral EC layer 3 go to distal CA1
what is the hillus reciprocally connected to?
to the DG
what does inactivation of the medial septum do in rodents? how was it tested?
impairs memory! rats can’t remember where the platform is in the water maze anymore
what type of memory is encoded in the hippocampus?
episodic memory (type of declarative memory)
what kind of hippo lesions disrupt memory performance in the water maze?
mostly dorsal lesions
how did they test for how long it takes for memory to move from the hippo to the cortex?
- they shock a rat at the same time as a tone: rat associates tone with shock
- they lesion the hippo after 1, 7, 14 or 28 days
- then test if the rat freezes when it hears the tone to see if it remembers the tone-shock association
what were the results of the tone-shock pairing and hippo lesions experiment? what can we conclude?
when lesioning the hippo after 28 days, the rat remembers the tone-shock pairing (freezes when hearing the tone), meaning the memory moved to the cortex
what do you call memory that moved from hippo to the cortex?
semantic memory
what is high pass filtering used for in extracellular recordings?
filter out the frequencies below 800Hz (local field potential) to look at higher frequencies only (spikes)
where are neurons that encode the location of the animal located?
in the medial temporal lobe
name the 3 types of neurons that encoded animal’s location
grid cells, head direction cells, place cells
what hippocampal neurons fire everywhere (at any location)?
interneurons are not place specific
what happens when rat’s medial forebrain bundle MFB stimulation is paired to a specific place cell during rat’s sleep?
the rate run’s to the location encoded by the place cell!
head direction cells have been recorded in rat pups as of when?
3-4 days before they open their eyes
what part of the brain had head direction, place and grid cells?
entorhinal cortex
what type of location cells are found in the hippocampus?
only place cells
what are angular velocity cells?
cells that fire when the animal turn its head in a specific direction
head direction cells can be tuned to what?
clock wise vs counter clockwise
where are head direction cells found?
- lateral mammillary nucleus
- anterior dorsal thalamic nucleus
- postsubiculum
how is the tuning curve of head direction cells in the lateral mammillary nucleus vs the anterior dorsal thalamic nucleus?
- lateral mammillary nucleus = wide tuning curve
- anteriodorsal thalamic nucleus = narrow tuning
what is the difference between ADN (anterior dorsal thalamic nucleus) and PSC (postsubiculum) head direction cells?
ADN HD cells fire before the stimulus and anticipate the head movement.
PSC neurons fire when the head actually turns
ADN head direction depend on what? how did they test this
on vestibular inputs;
they induced vestibular system lesions with sodium arsanilate in the inner ear and it decreased the firing rate of ADN HD cells
what other brain area was lesioned to test the role of vestibular input on ADN HD cells?
dorsal tegmental nucleus, the last part of the vestibular circuit
what were the results of dorsal tegmental nucleus lesions on ADN HD cells firing?
caused least fine tuning for head direction
what did lesions to the lateral mammillary nucleus do to ADN HD cells?
almost completely decreased the firing of head direction cells
HD cells in what region required input from ADN? how did they find that?
postsubiculum; ADN partial lesion leads to big widening of presubiculum HD cells tuning curve
what brain area that connects to ADN is not necessary for ADN HD cells function?
postsubiculum (postsubiculum lesions don’t affect ADN firing)
so far the data suggests that an interaction between what brain areas is critical for generating HD cell signal?
DTN (dorsal tegmental nucleus) and LMN (lateral mammillary nucleus)
they recorded ADN HD cells activity and found that it correlated with what?
with the error the rat made finding its way back in the dark
ADN HD cell firing corresponding with heading erros means that HD cells act as what?
internal compass
what happened to HD cells (i assume ADN HD cells) when rat went upside down? what does that mean?
no more firing; rats don’t have HD cells for upside down
what are the 3 models used to explain 3D encoding of HD in bats?
- pure azimuth cell: only fire when looking in a quadrent
- pure pitch cell: only fire when looking down
- azimuth and pitch cell mix
what cells are active during sleep?
ADN HD cells
how do ADN HD cells fire during sleep?
in cycles, going around the 360°
almost all cell in hippocampus are?
place cells
how did expanding the environment affect place field cells?
the firing field of place cells expanded with the environment
the taxi driver human computer game showed evidence for the presence of what type of cells in humans?
hippocampal place cells
how did they test for rodents encoding of 3D space?
- cage experiment, making them go upside down
- staircase experiment
do rodents place cells code for 3D?
no (place cells were firing at almost every level of the staircase)
what are attractor states?
pattern completion (assuming a pattern with little info)
pattern separation (seeing the 2 possible patterns)
what information allows us to fall into pattern separation?
having a big change in input (higher difference between 2 images)
‘Remapping’ of hippocampal place cells between contexts: what is global remapping?
when presented to 2 identical rooms, the hippocampus creates 2 separate maps in which the same neuron will fire at different location
‘Remapping’ of hippocampal place cells between contexts: what is rate remapping?
when presented twice to the same room in which things have changed, the hippocampus change the rate of fire; the same neuron fires at the same location but at different intensities in each room
in what context does global vs rate remapping happen?
- small change of input between 2 environments = rate remapping
- big change in input = global remapping
what happened to animal’s place cells when they were put in different rooms that slowly changed from square to circle
the place cells fire normally until the animal realises its a new room, global remapping happens (clear cut)
why do place cells do rate remapping?
to signal memory
how was rate remapping showed in an experiment?
asking an animal to turn left or right: some place cells fired more when turning right or left
what part of the hippo generates place cells?
CA1; it generates the spatial map
how did CPP (NMDA receptor blocker that blocks LTP) affect place cells?
it abolished long-term stability of newly formed place cells (can make new place fields but can’t retain the info)
what did they find when looking at the entorhinal cortex for place field signal?
nothing
what happened when they cut the connection from CA3 to CA1? what can we conclude?
place cells were not affected, therefore place cells originate after CA1 (in CA3)
what happens in the water maze if you lesion LEA (lateral entorhinal cortex)?
the animal perfroms well in the water maze. no effect
what happens in the water maze if you lesion MEA (medial entorhinal cortex)?
the animal struggles in the water maze (place cells are affected)
after realizing that MEA lesions affect water maze experiment, they recorded MEA. what did they find?
beautiful place fields
where in MEA did they find place fields?
dorsal MEA
MEA recording found that each neuron had..?
multiple place fields
what about ventral MEC? (MEA = MEC)
neurons there had weak spatial tuning, unlike dorsal
what pattern of activity was found in MEC place field when the animal was put in a large environment?
hexagonal grid of fields; equilateral triangles between place field; from that came grid cells
what happened to the grid cells in MEC in the dark?
their place fields persist! must be keeping track of the animal’s movement
what is one different between grid cells and place cells?
grid cells will always be grid cells no matter if the environment changes. Place cells change depending on the environment.
when do grid cells form?
they immediately start forming a grid field when entering a new environment
when did they find the most activity in grid cells/entorhinal cortex?
when an animal OR HOMUAN moves at a 60° angle, in line with the lines of the grid field
how does speed affect the activity of human’s entorhinal cortex?
faster speed = more activity
what occurs at the same time as global remapping of place cells?
realignment / remapping of grid cells / shift of grid field
they made the rats run in an 18m long tunnel and found what when measuring the activity of MEC?
dorsal MEC had more and smaller place fields,
ventral MEC had less but bigger place fields
they did the same experiment in the hippocampus. what did they find?
progressive increase in place cells from dorsal to ventral hippocampus (place fields get way bigger in ventral hippo)
this link in entorhinal and hippocampus grid / place fields widening led to what conclusion?
grid cells drive hippocampal place fields
what happened to GRID CELLS in a multi-compartmental environment?
grid fields code each hallway as if it was the same… they don’t make triangles patterns anymore
what happened to PLACE CELLS in a multi-compartmental environment? (hippo)
they also code for each hallway independantly, not forming a pattern (re-listen some of that class cus what)
the fact that hippo place cells and entorhinal cortex grid cells respond the same way to a multi-compartmental environment proves what?
that the place field signal in hippocampus comes from the entorhinal cortex!
multiple grid cells with the same what project to one place cell?
they have the same center (a place field in the middle)
what other brain area acts like the hippocampus? (lesions has the same behavioral effects)
medial septum
more precisely what do lesions / inactivation of the medial septum do?
- they eliminate theta oscillations throughout the medial temporal lobe
- disrupt the triangle pattern of GRID cells
what drug did they use for medial septum inactivation?
mucimol
how did they test the model of grid cells projecting to place cells?
via septum inactivation, to see if it stops grid AND place fields
what did they find about place field when inactivating the medial septum? what does this mean?
animals can still form place fields! meaning that grid cells are not necessary for place cells :o
what are conjunctive cells?
grid cells that are also sensitive to head direction
what are boundary vector cells?
cells that fire in bands across the environment determined by the distance of the animal from a boundary in a certain direction
where are boundary vector cells and conjunctive cells found?
MEA medial entorhinal cortex
what is the now the model for place cells after boundary vector cells discovery?
boundary vector cells combine to make place cells
apart from grid cells, head direction cells, conjunctive cells, and boundary vector cells, what other localization cell type is found in the MEC?
speed cells
apart from place cells, what other memory-related cells are found in the hippocampus?
time cells (signal for WHEN)
why does it make sense for episodic memory to be located in the hippocampus?
because the main component of episodic memory is the context, including the environment (where) and timing (WHEN)
how did they find the MEC speed cells?
by letting rats run on treadmills and noticing that the firing rate of some MEC neurons followed the speed even when running sur place
how did they test for hippocampal time cells?
they made rats run on a treadmill in a delay zone and found cells that fired depending on how long the animal was running in the box
are time cells only in the hippocampus?
no ish… grid cells in EC also code for distance and time on a treadmill (animal isn’t actually moving)
give the characteristics of hippocampal theta oscillations
- 6-10 Hz oscillation in local field potential in hippocampus and related structures
- observed during exploration and attentive behaviors in rats, mive, bats, pigeon, monkeys, humans
- highly precise spike timing throughout the hippocampal structures
what is theta phase precession?
place cell has rhythmic firing that slightly precedes the theta oscillations because it oscillates faster than the extracellular recording of theta oscillation
when does the place field fire in the middle of a theta oscillation in phase precession?
when the animal is in the middle of the place field
where is phase precession observed in the brain?
in entorhinal layer II grid cells but not in layer III grid cells
how did they prove that the oscillations of the place cells come from the place cells themselves?
single cell recordings of entorinal layer II
what is the consequence of phase precession? explain
precise temporally structured call assemblies: in one theta cycle, you have info about where you are coming from and where you are going
how does the firing of the neuron changeswhen it enters its place field?
it goes from firing at 8Hz to firing at 9Hz when we enter the cell’s place field
what happens when the animal is still and sleep?
hippocampus stops firing in theta state and fires in short wave ripples + sharp waves
during what kind of sleep do sharpwave ripples occur?
slow wave sleep
what happens to place cells during sharpwave ripples?
place cells (pyramidal cells) reactivate! in the order that they were activated during the movement
why do we have sharpwave ripples in the brain?
hippocampus sequences out (replays) displacements when we are not moving to remember it and to send it to the cortex
researchers can estimate the animal’s location based on what?
on its place cell firing
sharpwave ripples trigger activity where in the brain?
in all of the cortex :o how info gets from hippo to the cortex?
they blocked the hippocampus when sharpwave ripples are about to happen and found what?
Blocking hippocampal sharpwave ripples impairs memory consolidation
