Theoretical and Computational Neuroscience

(Lecture 6)
 What We Have Learned!
Saltatory conduction down a myelinated axon. Action potentials are generated only at the nodes of Ranvier; between the
nodes, there is passive spread of potential.

2
 What We Have Learned!

Passive current:

Membrane conductances is
not dependent on voltage

Active current (The Hodgkin–Huxley Equations):

Sodium
Potassium
voltage gated
channels voltage gated
channels

m n
m n
m n
Membrane conductances is h n
dependent on voltage

3
 What We Have Learned!

Membrane potential
changes with time

4
Part 1 : Simple Models of Neurons

https://persistentself.net/neuro-needlework-2/
What We Have Learned!

and
What We Have Learned!

Different notations for membrane

potential
What We Have Learned!
 What We Have Learned!
applied current
dV
C  gK n 4 (V  VK )  gNa m 3 h(V  VNa )  gL (V  VL )  Iapp  0 Note that n∞ and m∞ are increasing functions
that approach 0 for hyperpolarizing currents and
dt approach 1 for depolarizing currents. Hence, n
dn and m become activated when the membrane is
 n (V )  n (V )  n depolarized. On the other hand, h∞ is a
dt generic leak decreasing function, so the Na channels
inactivate when the membrane is depolarized.
dm dh
 m (V )  m (V )  m,  h (V )  h (V )  h
dt dt It is also important to note that time constant for
m is considerably smaller than for n or h. Hence,
Na channels activate much faster than they
inactivate or K channels open.
inactivation
 (decreases with V)

much smaller than

the others
activation
(increases with V)
 What We Have Learned!

τm is so fast that m changes essentially instantaneously to follow m∞(V), i.e. that m(t)=m∞(V(t)). This eliminates the differential
equation for dm/dt=0. Note that the time scale of m is fast compared to the membrane time constant τ=RC of a passive
membrane, which characterizes the evolution of the membrane voltage when all channels are closed.
 Three Simple Models of Neurons in Rodent Brains
Hodgkin and Huxley modeled the giant axon of the squid. Since then, many similar models of neurons in
mammalian brains have been proposed. Here, we list three examples, which will be used throughout the
course. The models discussed here are called the RTM model, WB, and Erisir models.
Chapter 5
 Three Simple Models of Neurons in Rodent Brains

All three are of the form of the classical Hodgkin-Huxley model, but with different parameter values, different functions
α x and βx (remember that α x and βx determine the functions x ∞ and τ x ), and with the assumption that “ τ m=0 ,” that
is, m∞ (v )=m . Thus m is not a dependent variable any more, but a direct function of v .

τ m is very small for all v :

m∞ (v )=m
Three Simple Models of Neurons in Rodent Brains

Physical units used throughout the Borger book.

Three Simple Models of Neurons in Rodent Brains
 Three Simple Models of Neurons in Rodent Brains
RTM Model: Reduced Traub-Miles Model of a Pyramidal Neuron in Rat Hippocampus. This is a substantial simplification
of a model of a pyramidal excitatory cell in rat hippocampus due to Traub and Miles.

Types Of Neurons

Hodgkin and Huxley’s formulas are:

Source: https://www.vectorstock.com/royalty-free-vector/types-
neurons-structure-sensory-motor-neuron-vector-21218406
 Three Simple Models of Neurons in Rodent Brains
RTM Model:
 Three Simple Models of Neurons in Rodent Brains
RTM: Reduced Traub-Miles Model of a Pyramidal Neuron in Rat Hippocampus. This is a substantial simplification of a
model of a pyramidal excitatory cell in rat hippocampus due to Traub and Miles.

Types Of Neurons

Hodgkin and Huxley’s formulas are:

Source: https://www.vectorstock.com/royalty-free-vector/types-
neurons-structure-sensory-motor-neuron-vector-21218406
 Three Simple Models of Neurons in Rodent Brains

WB Model: Wang and Buzs aki proposed a model of an inhibitory basket cell in rat hippocampus. Basket cells are
inhibitory GABAergic interneurons of the brain, found throughout different regions of the cortex and cerebellum. Basket cells
derive their name from the fact that the branches of their axonal arbors form basket-like structures surrounding the cell bodies
of other cells.

Two different classes of inhibitory basket cells are

ubiquitous in the brain, the parvalbumin-positive
(PV+) basket cells, which contain the protein
parvalbumin, and the cholecystokinin-positive
(CCK+) basket cells, which contain the hor-
mone cholecystokinin. The PV+ basket cells are
called fast-firing because they are capable of
sustained high-frequency firing, and are known
to play a central role in the generation of gamma
frequency (30–80 Hz) oscillations. It is thought
that gamma rhythms are important for sensory
processing, attention, and working memory. The
WB model is patterned after the fast-firing PV+
basket cells.
Source:
https://www.researchgate.net/publication/12870505_Mutatio
Source: G. Gonzalez-Burgos and D. A. Lewis, NMDA Receptor Hypofunction, Parvalbumin-Positive ns_in_the_KCNA1_gene_associated_with_episodic_ataxia_typ
Neurons, and Cortical Gamma Oscillations in Schizophrenia, Schizophrenia Bulletin, 2012. e-1_syndrome_impair_heteromeric_voltage-
gated_K_channel_function/figures?
lo=1&utm_source=google&utm_medium=organic
 Three Simple Models of Neurons in Rodent Brains

WB Model:
 Three Simple Models of Neurons in Rodent Brains
A comparison between RTM and WB Models:
The most striking difference is that the spike afterhyperpolarization, i.e., the
hyperpolarization following an action potential, is far less deep in the WB
model than in the RTM model. The difference between the lowest value of v
and the firing threshold is about 15 mV in the WB model. This is in agreement
with experimental results for fast-firing inhibitory interneurons.

The spike afterhyperpolarization is less pronounced for the WB model than for
the RTM model because the maximal conductance densities and are
smaller.

Deeper afterhyperpolarization would be obtained if they were raised (exercise

5), or h and n made slower (exercise 6). In fact, the Wang-Buzs aki model
included a scaling factor φ in front of the formulas for α n , βh , α h and βn .
Wang and Buzs aki chose φ = 5. This choice is built into the equations as
stated above. However, they pointed out that reducing φ, which amounts to
reducing α , β , α , and βh , i.e., to slowing down h and n, makes
n n h
spike afterhyperpolarization more pronounced.
 Three Simple Models of Neurons in Rodent Brains

Erisir Model: Erisir et al proposed a model of an inhibitory interneuron in mouse somatosensory cortex.
With minor modifications the model takes the same form as the RTM and WB models, except that the
potassium conductance is , not .

Sodium
voltage gated Potassium
channels voltage gated
channels

m n
m n
m n
h n

21
 Three Simple Models of Neurons in Rodent Brains

Note that and are quite large in the Erisir model, even larger
than in the RTM model. As a result, the voltage rises almost to v Na
during an action potential, and falls almost to v K immediately
following an action potential. The leak conductance density is large
as well.
 Three Simple Models of Neurons in Rodent Brains
What is the significance of taking the potassium
conductance to be , not ? The main
answer is that it does not appear to matter very much.
In detail, but it has the following effects, which one
can see when comparing the figures:

1. As n rises to values near 1 during a spike, the

potassium conductance responds more rapidly
when the exponent is 2, not 4. Therefore the spike
termination mechanism becomes faster, and the spikes
become narrower.

2. As n falls to values near 0 following a spike, the

potassium conductance follows less rapidly when the
exponent is 2, not 4. This has the effect that the
hyperpolarization following a spike is deeper.

3. Surprisingly, even though the potassium current is

hyperpolarizing, and is greater than for
0 < n < 1, firing is slightly faster with than
With . In essence, this is explained by the fact
that the narrower action potentials in Fig. 5.4 allow
less time for deep inactivation of the sodium current
(Exercise 8).
Part 2 : Derivation OF The
Nernst Equation

EX
 Equilibrium Potentials For Ions!

If we insert K+-selective channels in the membrane, when the electrical gradient exactly balances the chemical gradient, K+ is said to be at
electrochemical equilibrium.
 Derivation OF The Nernst Equation

Chemical equilibrium:
 Derivation OF The Nernst Equation

The partition function for N molecules in an ideal gas is given by:

,
 Derivation OF The Nernst Equation

Our goal is to define the total chemical potential for ionic species X on each side of the membrane. Therefore, we will define for the total
chemical potential of X inside the cell, and for the total chemical potential of X outside of the cell. In isothermal diffusion we will have:

X X
μi −μ o =KT ln ( Pi / P o ) =KT ln ( n i / n o )

inside the cell

Outside of the cell

 Derivation OF The Nernst Equation

In isothermal diffusion we will have:

If the particle x is neutral then in equilibrium we will have and

inside the cell

Outside of the cell

 Derivation OF The Nernst Equation

EX
EX
 Nernst And GHK Equations

Nernst Equation and equilibrium potential GHK Equation and resting membrane potential