Computational Model of

Facilitation
M. Andrews & J. Ni
Overview
What is Short Term Facilitation?
Why Does Facilitation Happen?

2 Mechanisms

Spike Broadening Residual Calcium

Residual Calcium Mechanism
Residual Calcium
Ca

Ca
Ca
Ca
Ca

Ca Ca

Ca
Ca Ca
Ca Ca
Ca Ca
Ca
Building a Model
1. Need to set stimulus parameters
(Frequency, Stimulus length)

2. Need to set system parameters

(Membrane properties, Calcium
concentrations and fluxes)

3. Need functional relationship

between [Ca] and vesicle
release
(Sigmoidal function)
4. Model postsynaptic response
(Combine previous parameters into a
response function)
 Stimulus Parameters
1. Need to set stimulus parameters
(Frequency, Stimulus length)

2. Need to set system parameters

(Membrane properties, Calcium
concentrations and fluxes)

3. Need functional relationship

between [Ca] and vesicle
release
(Sigmoidal function)
4. Model postsynaptic response
(Combine previous parameters into a
response function)
 Stimulus Parameters
1. Need to set stimulus parameters
(Frequency, Stimulus length)
Sets frequency of stimulus
(like how we did in lab)
**User Controlled** i.e. 2, 10, 20, 50Hz

Period of time between stimuli

(calculated by 1/frequency)
ex. 2 Hz -> Period of 0.5 sec

The length of time that the

stimulus is applied
In lab this was controlled by
flipping the “STIM” switch
 System Parameters
1.
2. stimulusparameters
Need to set system parameters
(Frequency, properties,
(Membrane Stimulus length)
Calcium
concentrations and fluxes)

2. Need to set system parameters

(Membrane properties, Calcium
concentrations and fluxes)

3. Need functional relationship

between [Ca] and vesicle
release
(Sigmoidal function)
4. Model postsynaptic response
(Combine previous parameters into a
response function)
 System Parameters Adjusts for normalization of our
[Ca] vs. Vesicle release plot
We’ll talk about this later
2. Need to set system parameters
Sets the initial concentration of
(Membrane properties, Calcium
intracellular calcium
concentrations and fluxes)
Literature value: [Ca]in = 100 nM
-> approximated at 0 nM

**Determined based on Sets how much calcium enters

experimental results** per stimulus

Sets calcium clearance rate (by

calcium pump)

Proportionality between number

of vesicles released and EPSP
amplitude

} Membrane properties
Determined experimentally
 Sigmoid Generation
1.
3. Need functional
to set stimulus
relationship
parameters
(Frequency,
between [Ca] Stimulus
andlength)
vesicle
release
2. (Sigmoidal
Need to setfunction)
system parameters
(Membrane properties, Calcium
concentrations and fluxes)

3. Need functional relationship

between [Ca] and vesicle
release
(Sigmoidal function)
4. Model postsynaptic response
(Combine previous parameters into a
response function)
 Sigmoid Generation
3. Need functional relationship
between [Ca] and vesicle
release
(Sigmoidal function)
Sigmoids are of the form:

We used:

L = 1 (Curve’s max value)

x0 = 0.5 (Curve’s midpoint)
k = 8 (Steepness of curve)
 Modeling Response
4.
1. Model postsynaptic
Need to set stimulusresponse
parameters
(Combine previous
(Frequency, parameters
Stimulus length) into a
response function)

2. Need to set system parameters

(Membrane properties, Calcium
concentrations and fluxes)

3. Need functional relationship

between [Ca] and vesicle
release
(Sigmoidal function)
4. Model postsynaptic response
(Combine previous parameters into a
response function)
 Modeling Response
4. Model postsynaptic response
(Combine previous parameters into a
response function) Wha
t
disso in the co
nanc g
e do nitive
mea es th
n?! is
 Use Stimulus Parameters to make a loop to
Modeling Response repeat stimulus

1. Adds Influx Calcium to Internal Calcium

4. Model postsynaptic response for each stimulus
Ca
(Combine previous parameters into a
response function) 2. Calculates Transmitter Release based on
Internal Calcium using Sigmoid Function

3. Calculates EPSP Amplitude by multiplying

Transmitter Release by Proportionality
Wha
t
diss in the c
ona
Constant
nce ognitive
mea does th
n?! is
4. Uses RC Circuit Equation and Tau to
calculate Decay Profile

5. Adjusts new Internal Calcium

concentration using Calcium Clearance Ca
value

Repeat
Running the Model
Running the Model
Running the Model
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Voltage (mV)

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Voltage (mV)

The Moment of Truth (aka Science)!

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 But What About Facilitation?
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Voltage (mV)

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2 Hz Signal

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3
 Other Frequencies
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10 Hz Signal

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1 2 3 Time (s)
 Other Frequencies
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20 Hz Signal

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0 1 2 Time (s)
 Facilitation and Summation
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Voltage (mV)

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50 Hz Signal

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0 1 2 Time (s)
Assumptions and Simplifications
1. Assumed residual calcium mechanism
Residual Calcium

2. Normalized sigmoid

3. Ignored spontaneous activity

4. Assumed membrane properties and Ca

Calcium fluxes were constant

Ca
Why Are Computational Models Important?
Any Questions?