Week 4: A case study using rate neurons = Head Direction (HD) Cells Flashcards
HD Case study using
rate-coded neurons
Hippocampus and its nearby areas are important for
memory and spatial cognition/orientation
spatial cognition means….
the knowledge and processes used to represent and navigate in and through space
First hint that hippocampus important for memory formation is from famous case study H&M as… (3)
· HM had severe epilepsy that was drug resistant
· At the last resort, they cut both hippocampi (since hippocampus is typically the source of epileptic seizures)
· They figured out that HM could not form any new memories
A parallel stream of animal research (after H&M) using the Morris Water maze also revealed that the
hippocampus is fundamental for spatial navigation.
What does the Morris Water maze involve? (3)
rodents placed in a pool of water that is opaque
· The maze has a hidden escape platform that is just below the surface of the water and is in a fixed location of the maze.
· In the maze, the animals must search to locate the hidden platform
Morris Water Maze
Findings (Morris et al., 1982)
Rats who had no lesions to the hippocampus (control) took less time in swimming towards the platform , no matter what area they were dropped in the maze, as compared to rats who had bilteral lesions to the hippocampus.
Diagram of Morris Water Maze
Taube 1990 measured the neurons in the hippocampus and surrounding areas using a technique called
single cell recordings mostly with rodents
Single cell recordings methodology (3)
microdrives with electrodes are implanted chronically in rodents’ brain
·Once the animal recovered from this surgery, the rodent is allowed to remove freely from the box where there is a visual cue (e.g., white cue card) on the wall of the box which helps the animal orient itself to
The electrodes in the animal are moved slowly per day until they record spikes:
Single cell recordings technique allows us to know
what single neurons are doing in a behaving animal
Diagram of rodent single cell recordings
Cells that share characteristics of encoding both place and HDC found in
Presubicular and parasubicular cortices (Taube, 2007)
Plot of HD cells
Head directions are predominantly found in a large network of brain areas in Papez circuit (Taube 2007) such as (3)
o Entorhinal cortex
o The thalamus (lateral dorsal and anterior dorsal nuclei)
o Anterior dorsal thalamic
HD found in non-Papez circuit in brain like (3) (Taube, 2007)
Lateral dorsal thalamus
Dorsal striatum
Medial preecentral cortex
Diagram of areas where HD cells are found: what red, blue and green? (3)
Red = Pure forms of head direction cells
Green = Theta-modulated head directions
Blue = Theta-modulated structures that have no head direction cells
Reminder of theta is:
distinguished background oscillation in the membrane potential (similar to VoSC in the Lisman and Idiart model of WM)
Place cells are commonly found in the (2)
· subiculum and
in the entorhinal cortex ( Taube, 2007)
Two types of cells important for spatial cognition (2)
HD cells
Place cells
The general properties of HDC was first described by
Taube et al., 1990
HDCs can be depicted using a (2)
polar plot or
tuning curve with firing rate on ordinate axis and animal’s head represented on abscissa
Taube et al., (1990) HD cell Tuning graph (3) Example
Graph from single cell recording that is integrated over time
Animal will run around with box for 10-20 minutes where experimenters track where the animal is looking and firing rates of HD neurons
In this graph, a particular neuron emits few spikes at 90 degrees. But when animal is looking 200 degrees, every time during 20 minutes, this particular HD neuron vigorously emits more spikes (PREF DIREC)
Direction at which HDCs fire maximally is referred as the cell’s
- preferred firing direction
Place cell graph (3)
Let animal run around the box
Every time a specific place cell neuron fires AP you plot a red dot
Accumulates this data over 20 minutes of rodent running in box
Receptive fields, areas at which
which stimulation leads to response of a specific sensory neuron”
Different place cells and HD cells are distinguished by
their different receptive fields
Place cells have a receptive fields for
spatial location
HD cells have a receptive field for
head orientation
Whats the 3 uses of HD cells?
- Orientation is very important for navigation
- For grasping and pointing: If you want to reorient yourself and do some action like pointing somewhere in a specific direction
- To define a point of view = human spatial cognition
Different HD cells are distinguished by different receptive fields meaning in other words:
what direction is the preferred direction (i.e., emits most spikes)
In place cells have receptive fields meaning that a particular place cell neuron fires most
- vigorously at a particular location in the environment
From manipulations of single-cell recording of rodent (Taube, 1990), experiments found 3 main defining properties of HD cells are… (3)
Head direction cells depend on vestibular input
Cue cards control angular turning
HD drift in darkness meaning without any visual input, the animal loses its sense of orientation
Mizumori and Williams (1993) found HD cells drift in darkness as when rats are either blindedfolded or placed in complete darkness then preferred direction of HD cells
become less stable (disrupted) and begins to drift
Stackman and Taube (1997) found HDcs depend on vestibular input as
- neurotoxic lesions of vestibular labyrinth abolished HD cell signal in the AND for up to three months post lesion
vestibular input is the sensation in
changes of direction, movement and position of head
Taube demonstrated that the cue cards control angular turning (orientation)
what was the method?
Rotate cue card leads to…
This means HD is controlled by… (3)
HD cells recorded in a cylinder that contains a prominent visual cue (e.g., white cue card) attached to the box
They rotate this important visual landmark which leads to a corresponding shift in the preferred firing direction of HD cells
Thus, HD cells controlled by landmarks (Taube et al., 1990
Hypotheses from 3 main defining properities of HD cells (2)
HD used for navigation
When animal lost its way, HD cells have lost their stable directional tuning which makes them drift
Correct for drift in HD cells by
receiving feedback from visual cue
Correct for drift in HD cells by receiving feedback from visual cue
What is visual cell and seeing visual cue card ahead? (2)
- Visual cells that are somewhere in your visual cortex will provide feedback (i.e., meaning providing synaptic inputs at particular orientations to specific HD cells)
- In seeing a cue card ahead, a specific visual cell will be active and give strong synaptic input to the appropriate and correct HD cell
Diagram of visual cells feedback correcting for drift
Even in darkness, the directional firing preference of HDC was maintained - Mizumori and Williams 1993
briefly
Another property of HDcs is independent of animal’s ongoing behaviour in experiment as
The firing of a head direction cell was maximal at the preferred direction and unaffected by whether the animal was eating, grooming, earing, walking running etc..
Questions for HD cells model (2)
How is HD activity sustained when head is still at a certain heading and even without any visual inputs (i.e., darkness)
How is HD updated after each head turn?
HD sustained firing at given location
Taube (2007;1990) found HDC firing is largely unaffected by pitch/roll of animal’s head within 90 degrees of horizontal plane as
long as the animal’s head is in a given cell’s directional range, cell firing will continue whether the animal is moving or still and largely independent of the animal’s ongoing behaviour
HD cells must cover
0 to 360 degrees uniformly
We get a tuning curve of a single HD cell neuron by (2)
As the animal moves around our chosen neuron fires at varying rates depending on the heading
Summing all those activities and dividing by the total time we get a tuning curve
Diagram of tuning curve of single HD cell
In a tuning curve of HD cell it has firing rate ______ as a function of ___
Its data is ____
(2)
firing rate of a single HD neuron as a function of heading
Its data is accumulated over time
Tuning curve of all HD neurons given one heading diagram
In tuning curve of all HD neurons there is line of bunch of
neurons
In tuning curve of all HD neurons , the ___ HD neuron is active
red
Tuning curve where updating heading and turning head to another direction diagram
What happens when turning my head in another direction in tuning curve? (3
A different HD neuron is maximally active compared to other 2 graphs
Now that the heading is changed, the activity of HD cells is shifted so the red neuron is less active and gives smaller contribution to this orientation
As animal moves, tuning curve of firing rate of HDC shifts with different heading directions so different HDC get smaller or large contributions.
The defining characteristic of this case study is finding the synaptic connections that give us (tuning curve pattern, more specifically…) - (2)
sustained activity when the head is still, even in darkness (at least for a while) i.e., without sensory feedback
Able to shift the activity pattern of HDCs across the line of neurons
HDCs most active in a particular direction sustain their activity when the head is still (even in darkness) by…
short-range excitatory connections + long-range inhibitory connections (2)
It is exciting itself as well as exciting neighbouring HDC near them due to having short-range excitatory synaptic connections (recurrent connections)
Also has long-range inhibitory synaptic connections to distant HDC to suppress its activity
Diagram of HDCs having short-range excitation and long-range inhibition
There is close-range excitation and long-range inhibition for each
HDC neuron in the ring
How to shift the activity pattern of HDCs across the line of neurons? (3)
- These line of neurons active will have an offset inhibition in the direction opposite of a turn and offset excitation in the direction of a turn.
- These connections will be active only when the head is turning (dependent on velocity)
- We need double of these connections, one for clock-wise and counter-clockwise head turns.
Diagram of shifting activity packet across ring of HDC neurons
To turn clockwise we need to excite
nearby HDCs to the right (blue)
To turn anti- clockwise we need to excite
nearby HDCs to the left (purple)
Reminder: what gives us sustained activity for
symmetric short-range and long-range inhbition
Reminder: what gives us capability to turn our head and shift activity pattern across ring of HDCs neuron?
Velocity-dependent asymmetric excitation and inhibition
Paper that used firing rate model to explain spatial orientation in HDCs
Zhang et al., (1996)
In Zhang’s paper, equation is:
change of activation over time = -a + (weight * rate)
Zhang’s paper have W as a matrix
all sender/receiver combinations and r is a vector of firing rates of all neurons
Some of the wij will be 0 so meaning in Zhang will be
zero, those for sender-receiver neuron pairs that are not connected by a synapse
Zhang’s concise equation for each neuron in the network
In Zhang’s concise equation, each equation needs to be updated
separately which was the case in lamprey spinal cord and WM model
Updating orientation Zhang 1996
diagram (2)
odd weights lead to…
the asymmetric component is…
odd weights (call them asymmetric) lead to shift of the activity bump across the neurons
Recall the asymmetric component is velocity dependent
Two possible behaviours when giving external stimulus to HD ring in Zhang 1996 model
Shift and reset
Zhang found that the internal
direction maintained by HD cell networks is calibrated by external input from a local-view detector
If the activity of HD cell network is maintained at 180 degrees but the heading is 200 degrees then the
external input from the local-view detector will induce a shift in its activity towards 200
Reset is shown if the excitation of HD cells in the network is too far away from the actual orientation of heading then the
external input from the local-view detector will produce a new estimate –> this resets the heading.
Diagram of reset and shift
The HD ring network is an example of a
continuous attractor network (CAN)
HD ring network is an example of CAN because… (3)
o Place the activity anywhere you wanted in our line of neurons
o Shift it and make it come to rest at a new position
o It can sustain its activity as connectivity pattern is same for each neuron when heading is still at a certain orientation
If precise connections are perturbed? (like deleting some HDC cells) in ring of HDC then - (4)
All activity of HDCs converge to different locations and at the end only represent a subset of all possible orientations
The continous attractor becomes a discrete attractor
Certain HDC attract the activity bump
Discrete basins of attractions (circle)
Continous attractor def and example (2)
we can place the ball anywhere
(our symmetric connections maintain the activity packet in place)
Discrete attractor ball def and example (2)
Given a bit of time, the ball settles in one of
Several valleys (basins). Locations between valley are unstable.
Is this what happens to HD during aging due to neuron loss?
Benefits of this HD (4)
Best model of HD we have
Allows us to explain how internal sense of direction is coded and maintained
Don’t have to make use of spikes, let alone ion channels (assuming all info about direction is encoded in firing rate of network)
Good case of rate-coded neurons
Problems of HD CAN - (2)
- How could the brain learn and maintain such precise connections? Neurons die off, affected by biological noise (e.g., temperature etc…)
o Partial answer: see reference Cacucci
