Borges Book Summary chapter 1-2-3-5-9

1.1. Biological vocabulary

NEURON→ fundamental unit of brain (100billions)
➔ consist of: Soma (cell body) and branching projections: dendrites→input -axon
→output.
➔ Filled and surrounded by solutions (water + dissolved ions) called intra-
extracellular fluids
o [𝑁𝑎+ ]𝑒𝑥 ≫ [𝑁𝑎+ ]𝑖𝑛 , [𝐾 + ]𝑒𝑥 ≪ [𝑘 + ]𝑖𝑛 , [𝐶𝑙 − ]𝑒𝑥 ≫ [𝐶𝑙 − ]𝑖𝑛 , [𝐶𝑎2+ ]𝑒𝑥 ≫ [𝐶𝑎2+ ]𝑖𝑛
Some ions are not capable to cross the cell membrane
Cell Membrane contains→ Ion specific channels allow a specific type of ions to pass
through it
→Active pumps → Sodium-potassium pumps(most famous)
actively transport 3 𝑁𝑎+ out of the cell and brings 2 𝑘 + inside
the cell
Membrane potential (v)→ Difference in electrical potential between interior- exterior of the
membrane
➔ Equilibrium potential of a nerve cell→ -70 mV (millivolt)
➔ Hyperpolarization of v → v more negative than the equilibrium→ inhibitory input
➔ Depolarization of v → v more positive than the equilibrium→ excitatory input
Action potentials → brief surges in the membrane potential generated by excitation of nerves and
muscles
➔ Spikes or fires → when a neurons generates an action potential
➔ Inter-spikes intervals → intervals between 2 action potentials
➔ Action potentials are sodium-based (most) or calcium-based (some)
➔ Sodium-based action potentials:
o The membrane open the sodium cannels (input from other nerve cells)→
Na+ ions (positive charge) enters the cell (because more outside than
inside)→ increase the membrane potential (often above 0mV)→sodium
channels start inactive-closing (within 1-2 ms)→ elevate value of v causes K+
channels to open→ K+ (positive charge) leaves the cell ( because more inside
than outside)→ v falls.
o Delayed rectifier current→ is a current carried by the K+
▪ Delayed→ because the K+ channels open with a delay.
▪ Rectifier→ because the K current results in the return of v to its
equilibrium
➔ Firing threshold→ voltage threshold at which the neuron voltage rises, then rises
rapidly.
➔ Axon hillock→ spatial location in which the voltage spike is originated→near the
cell body on the axonal side.
➔ Axonal terminals→ Tips of the branches of the axon at which the spike arrives
travelling down to the axon. It is very close to the membranes of other neurons
 ➔ Synapses → locations of contacts between 2 neurons
➔ Synaptic cleft→ is the space between the presynaptic (order of 20nm)
➔ Neurotransmitter→ chemical released by the synapses at the axon terminal caused
by the action potential arrivals.
o When released they diffuses across the synaptic cleft to the post-synaptic
membrane, where it binds to specialized receptors→ leads to the opening of
ion channels→ change the v of the post-synaptic neuron.
➔ Types of neurotransmitters (released by different type of neurons):
1. Glutamate → excitatory neurotransmitter→ when binds to a receptor the effect is a
depolarization of the post-synaptic membrane (rise the membrane potential)
- Neurons that released an excitatory neurotransmitter → called excitatory neurons
- Neurons that release glutamate→ called glutamatergic
- Excitatory neurons in the brain have a cell body of pyramidal shape → pyramidal
neurons
- Two important Glutamate receptors classes:
o AMPA receptors and NMDA receptors.
AMPA and NMDA are ionotropic→ the receptor itself is an ion channel which
opens when the glutamate bind to it
2. GABA (gamma-aminobutyric acid)→ inhibitory neurotransmitter→ when binds to a
receptor the effect is a hyperpolarization of the post-synaptic membrane.
- Neurons that released an inhibitory neurotransmitter→ called inhibitory
neurons
- They are typically interneurons→ neurons whose axons connect only to nearby
neurons
- Neurons that release GABA→ called GABAergic
- GABA receptors:
o GABAA receptors→ When GABA binds them→ chloride channels open→
since [𝐶𝑙 − ]𝑒𝑥 ≫ [𝐶𝑙 − ]𝑖𝑛 → influx of chloride (negative charged)→
hyperpolarizing of the post-synaptic cell
o GABAB receptors→ are metabotropic → when GABA binds to it→ second
messenger cascade (is a signaling cascade) is set in motion→ indirectly leads
to the opening to the K+ channels→ result in flow of K+ out of the cell→
hyperpolarizing of the post-synaptic cell
➔ Neurotransmitters can act in both excitatory and inhibitory ways
➔ Single neuron can release both glutamate and GABA
➔ Post-synaptic currents→ are the ion currents triggered by the binding of the
neurotransmitter to the receptor in the post-synaptic membrane. Transient currents
➔ The ion channels that open due to neurotransmitter binding to the receptors close
after a brief time.
➔ Post-synaptic currents time:
o AMPA receptor-mediated → only few ms
o NMDA receptor-mediated → last for 10s-100s ms
o GABAA receptor-mediated→ 10s or less ms
o GABAB receptor-mediated→ 10s or 100s ms
 ➔ Major mechanism of neuronal communication in the brain→ Action potential-
triggered released of neurotransmitters→ called Synaptic or chemical
communication
➔ Second important mechanism→ called gap-junctional or electrical communication
o Involves gap junctions→ openings in both neuronal membranes allows the
direct flow of ions from one neuron into the other

➔ Synaptic plasticity→ is the strengthening or wakening of synaptic connections

o Mechanism of synaptic plasticity include→ changes in the quantity of
neurotransmitter released and changes in the number of post-synaptic
receptors

1.2. Mathematical Notation

Mathematical background on exponential and logarithmic functions

1.3. Physical Units

2. The Nernst Equilibrium

Electro-diffusion theory
➔ Ion concentrations and electrical potential are different inside and outside the cell
membrane
➔ Convention: electrical potential in the extracellular fluid is zero
o Potential difference is what have meaning
o Membrane potential 𝑣 is the electrical potential on the interior side
➔ Assume:
o a membrane potential 𝑣 imposed artificially→ es. attaching a battery to a cell
o ions of some species X could diffuse through the membrane through
channels
o There aren’t ion pumps actively transporting X-ions across the membrane
→ If 𝑣=0→ [𝑋]𝑒𝑥 = [𝑋]𝑖𝑛
→If 𝑣≠ 0→ electrical forces come into play
→Denote z is the number of unit charges carried by one X-ion
▪ if z> 0 and 𝑣<0 and X-ions are attracted into the cell→ [𝑋]𝑖𝑛 rise→ but
increase cannot continue indefinitely
→Denote 𝑊𝑒 amount of work done against the electrical field when moving one
ion from outside to inside of a cell
▪ Definition: 𝑊𝑒 = 𝑧𝑞𝑣 where q is a unit charge i.e charge of a
positron
 → Denote 𝑊𝑑 amount of work done against the concentration jump when
moving one ion from the outside to inside.
▪ Diffusional effect is proportional to the temperature.
(higher temperature→ higher diffusion)
[𝑋]
▪ 𝑊𝑑 increases the ratio [𝑋] 𝑖𝑛 increases
𝑒𝑥
[𝑋]𝑖𝑛
▪ Formula: 𝑊𝑒 = 𝑘𝑇𝑙𝑛( ) where k denotes the Boltzmann’s
[𝑋]𝑒𝑥
constant

→Diffusional and electrical effect are in equilibrium if

• 𝑊𝑒 + 𝑊𝑑 = 0
➔ Using the previous equation → substituted in the equilibrium
o Becomes 𝑣 = 𝑣𝑥
𝑘𝑇 [𝑋]𝑖𝑛
• 𝑣𝑥 = 𝑙𝑛( )
𝑧𝑞 [𝑋]𝑒𝑥
This equation is called Nernst equilibrium potential of ion species X
➔ Typical value of Nernst potential:
o 𝑣 never gets high as 𝑣𝑁𝑎 → sodium will flow into the cell when sodium channels
are open. The same holds for calcium

➔ If 𝑣 ≠ 𝑣𝑥 and there are X-channels open, there is a flow of X-ions across the cell
membrane, and therefore an electrical current, 𝐼𝑥 , carried by the ions.
➔ This current is assumed to follow Ohm’s law:
𝐼𝑥 = 𝑔𝑥 ( 𝑣𝑥 − 𝑣)
o Where 𝑔𝑥 is a conductance (reciprocal of resistance) → proportional to the
number of the open channels.
o 𝐼𝑥 > 0 if the current is inward, 𝐼𝑥 < 0 if the current is outward.

3. The Classical Hodgkin-Huxley (H-H) ODEs

Physical mechanism of→ electrical impulses generated by nerve cells and its travel along
axons.
➔ Space clamp technique→ threaded a silver wire along the axon to eliminate the
spatial variations in the membrane potential v
➔ Assumption→ nerve cell membrane acts as capacitor→ separating 2 charge layers.
o Cv=Q Where Q is the separated charge and C is the capacitance
(constant)
➔ If Q and v depend on time t
𝑑𝑣
o 𝐶 = 𝐼𝑡𝑜𝑡𝑎𝑙
𝑑𝑡
➔ H-H hypothesis→ 𝐼𝑡𝑜𝑡𝑎𝑙 = 𝐼𝑁𝑎 + 𝐼𝐾 + 𝐼𝐿 + 𝐼→ I= sodium-potassium-leak- injected
currents
➔ Assume 𝐼𝑁𝑎 , 𝐼𝐾 , 𝐼𝐿 obey to Ohm’s law→ 𝐼𝑥 = 𝑔𝑥 (𝑣𝑥 − 𝑣) where x= Na, K, L
➔ 𝑣𝑁𝑎 , 𝑣𝐾 , 𝑣𝐿 called also reversal potentials
➔ Conductance 𝑔𝑁𝑎 and 𝑔𝐾 track changes in v →
o And are constant conductance
o m, h and n are time-dependent dimensionless quantities varying between 0
and 1
o m and h denote the sodium open m- and h-gates (independent from each
other)
▪ 3 gates of one type m and 1 gates of type h→ in series
o n is the number of in series gates for a potassium channels→ 4 independent
gates 𝑛4
o n, h and n are called gating variables when , = largest possible
conductances
➔ in H-H model, m, h and h→ obey simple first order ODEs as
𝑑𝑥 𝑥 (𝑣)
▪ = ∞ where x= m, h, n
𝑑𝑡 𝜏𝑥 (𝑣)
➔ If 𝑥∞ and 𝜏𝑥 were constant
−𝑡 −𝑡
▪ 𝑥(𝑡) = 𝑥(0)𝑒 + 𝑥∞ (1 − 𝑒 )
𝜏𝑥 𝜏𝑥

o Assume 𝜏𝑥 always positive

o x(0) starts weighted by 1 when t=0, then decays to 0 exponentially fast
o 𝑥∞ its weight starts at 0 when t=1, then converges to 1 exponentially fast
o x(t) moves from x(0) to 𝑥∞ exponentially fast
o the time it takes is 𝜏𝑥
➔ x(t) converges to 𝑥∞ exponentially with time constant 𝜏𝑥
➔ means m, h, n move towards 𝑚∞ , ℎ∞ , 𝑛∞ exponentially with time constants
𝜏𝑚 , 𝜏ℎ , 𝜏𝑛
➔ m, h, n respond to changes in v → the response velocity is measure by their 𝜏𝑥
➔ Observation based on the graph of m, h, n and their 𝜏𝑥 in the H-H model
 1. 𝜏𝑚 approximately 10 times smaller than 𝜏ℎ and 𝜏𝑛 → m responds to changes in v
much faster than h and n→ H-H equations are a slow-fast system (different time
scales)
2. 𝑚∞ and 𝑛∞ are increasing functions of v→ m and n are activation variable
i. As v rises→m-gates open→ n-gates open, 10 times slower than m-gates
ii. m and n are activation gates
3. ℎ∞ is a decreasing function of v→ h is an inactivation variable
i. As v rises→ h-gates close, 10 time slower than m-gates open
ii. H-gate is an inactivation gate
➔ Leak conductance 𝑔𝐿 is constant →
➔ Summarize H-H model of space clamped squid axon:

➔ System of 4 Odes unknown function v, m, h and n.

➔ Dividing both sides by the total membrane area→ obtain capacitance, conductance
and current per unit membrane area
➔ The constants are:

o is very much smaller than the other two

o The leak conductance is crucial for the behaviour of the model→ reason:
▪ Between 2 voltage spikes, is not very small in comparison with
• → sodium and potassium are closed between voltage
spikes, while the leak channel remain open
𝑑𝑥
➔ The ODE can be rewritten as = 𝛼𝑥 (𝑣)(1 − 𝑥) − 𝛽𝑥 (𝑣)𝑥
𝑑𝑡
➔ Relation between the parameters 𝑥∞ (𝑣) and 𝜏𝑥 (𝑣) with 𝛼𝑥 (𝑣)and 𝛽𝑥 (𝑣)
o and or and

➔ Interpretation→ 𝛼𝑥 as the time rate at which closed gates open, 𝛽𝑥 as the time rate
at which the open gate close.
➔ 𝛼𝑥 and 𝛽𝑥 are easier to fit with simple formulas because they are monotonic
functions of v.
H-H model for action potential
➔ Action potentials are generated when m-gates open in response to an initial
depolarization→ causing sodium current into the cell→ which rises further v → the
rise of v is terminated when h-gates close→ end of inflow of sodium→ n-gates
open, leading to an outflow of potassium
3.2. Activation, Inactivation, De-activation and De-inactivation
 ➔ m and n are activation variables→ an increase in them as result of depolarization→
causes activation of the current→ decrease in them as result of hyperpolarization→
causes de-activation of the current
➔ h is an inactivation variable→ a decrease in it as result of depolarization causes
inactivation of the current → an increase in it as a result of hyperpolarization causes
de-inactivation of the current
➔ De-activation in not the same as inactivation and de-inactivation is not the same as
activation

Software Experiment 0 Assignment- Nernst & Rest Potentials

1. Explain the theory behind the Nernst Potential, i.e., using the basic laws
➔ Consider two solution with different concentration of an ionic species with an open channel between
them that allow that type of ions to pass through the semi-permeable membrane.
➔ By diffusion law, ions will diffuse from the compartment at higher concentration to the one at lower
concentration.
➔ As the diffusion continues, will have developed across the semi-permeable membrane an electrical
charges that contrast the diffusion process by applying an electrostatic forces against the electrical
field, by the electrostatic law.
➔ The Nernst potential is indeed the equilibrium voltage for that specific ions across the membrane at
which diffusion forces are balanced by the electrostatic forces→ resulting in a net ionic flux equal to
zero.

2. What are the approximate Nernst potentials for K+, Na+, and Cl in a neuronal cell? What do they
depend on?
➔ 𝑣𝐾 = −90 𝑚𝑉, 𝑣𝑁𝑎 = 60 𝑚𝑉, 𝑣𝐶𝑙 = −70 𝑚𝑉.
𝑘𝑇 [𝑋]𝑖𝑛
➔ As a Nernst potential is defined as 𝑣𝑥 = 𝑙𝑛( ). The main difference between a Nernst potential
𝑧𝑞 [𝑋]𝑒𝑥
for one specific ion and another is the concentration of that ion inside and outside the cell.
o [𝑁𝑎 + ]𝑒𝑥 ≫ [𝑁𝑎+ ]𝑖𝑛 , [𝐾 + ]𝑒𝑥 ≪ [𝑘 + ]𝑖𝑛 , [𝐶𝑙 − ]𝑒𝑥 ≫ [𝐶𝑙 − ]𝑖𝑛 (ex= extracellular, in= intracellular)
o As for convention it is assumed that the electrical potential in the extracellular fluid zero
o Na has positive charge and more concentrate insiede the cell so 𝑣𝑁𝑎 is positive
o K has positive charge but more concentrate outside the cell so 𝑣𝐾 is negative
o Cl has negative charge and more concentrate insiede the cell so 𝑣𝐶𝑙 is negative

3. Write the equation for calculating the Nernst potential.

𝑘𝑇 [𝑋]𝑖𝑛
𝑣𝑥 = 𝑙𝑛( ).
𝑧𝑞 [𝑋]𝑒𝑥
➔ The Nernst potential is directly proportional to T, the Temperature and to the logarithm of
concentration of that ion x inside and outside the cell membrane.
o Where k denotes the Boltzmann’s constant k= 1.38 × 10−23 J/K ,
o z is the number of unit charges carried by one X-ion
o q is a unit charge i.e charge of a positron

4. What will decreasing the internal concentration of K+ do to its Nernst potential?

𝑘𝑇 [𝐾]𝑖𝑛
𝑣𝐾 =
𝑙𝑛( )
𝑧𝑞 [𝐾]𝑒𝑥
➔ As the internal concentration of K+ decrease inside the cell the Nernst potential for the potassium
will be more negative because the logarithm will be more negative.
5. How do the individual Nernst potentials determine the resting membrane potential?
Assuming that only one ionic species is present in the system, and/or channels for only one ionic species
are present, then Nernst potentials for these ionic species is also be the membrane resting potential

6. What is the GHK equation?

➔ Is Goldman Hodgkin Katz Equation that define that the resting, Vm, depends on the concentration
gradients and on the relative permeabilities (Pi) to Na, K and Cl

7. If the permeability to Na+ is increased, how would this affect its Nernst potential?
➔ The Nernst potential does not depend on the degree of permeability of the membrane to the ion, but
on the concentration between inside and outside of ions

8. If the permeability to Na+ was increased, how about the resting potential of the cell?
➔ The concentration of Na+ is more outside than inside the cell, so if the permeability to Na+ increase,
the resting potential will increase as well because it will be more Na+ going inside the cell rising the
membrane potential. As is visible in the GHK equation, the permeability multiplied both
concentrations (inside and outside), with higher concentration outside it will give a higher value of
the multiplication than the permeability multiplied by the concentration of Na+ inside the cell.

9. Of the major ions contributing to the resting membrane potential, which is the one that has a larger
intracellular concentration compared to its concentration outside?
➔ The type of ions that has larger intracellular concentration are potassium ions, K+, which are
[𝐾 + ]𝑒𝑥 = 150 mM and [𝑘 + ]𝑖𝑛 = 15 mM (in a squid axon)

10. If the external concentration of Na+ is increased, what will happen to the resting potential of the cell?
What if the external concentration of K+ is increased?
As shown in this figure (from Dr.Nair Slides) the resting potential is largely independent of the external
Na+ concentration, while it strongly depends on the external concentration of K+→ so it the external
concentration of K+ increase the membrane resting potential will strongly increase (exponentially)
Three Simple Models of Neurons in Rodent Brains
Description of 3 model neurons→ RTM model, WB, and Erisir models.
→Different parameter values, different functions αx and βx

5.1 Reduced Traub-Miles Model of a Pyramidal Neuron in Rat Hippocampus (RTM)

→ A pyramidal excitatory cell in rat hippocampus due to Traub and Miles

5.2 Wang-Buzsaki Model of an Inhibitory Interneuron in Rat Hippocampus

➔ model of an inhibitory basket cell in rat hippocampus

➔ basket due to the branches of their axonal arbors form basket-like structures
➔ different classes of inhibitory basket cells are ubiquitous in the brain:
 o the parvalbumin-positive (PV+) basket cells→ contain the protein parvalbumin→ fast
firing→ they have a central role in the generation of gamma frequency (30–80 Hz)
oscillations→ gamma importance→ for sensory processing, attention and memory
o cholecystokinin-positive (CCK+) basket cells → contain the hormone cholecystokinin.

➔ hyperpolarization following an action potential, is far less deep in the WB model than in the
RTM model
➔ The spike afterhyperpolarization is less pronounced for the WB model than for the RTM model
because the maximal conductance densities gNa,max and gK,max are smaller

5.3 Erisir Model of an Inhibitory Interneuron in Mouse Cortex

➔ model of an inhibitory interneuron in mouse somatosensory cortex
➔ Potassium conductance is 𝑔𝐾 𝑛2, not 𝑔𝐾 𝑛4→ but it doesn’t matter very much
➔ n rises to values near 1 during a spike, the potassium conductance responds more rapidly
when the exponent is 2, not 4. →spike termination mechanism becomes faster, and the spikes
become narrower.
➔ n falls to values near 0 following a spike the potassium conductance follows less rapidly when
the exponent is 2, not 4→has the effect that the hyperpolarization following a spike is deeper
Chapter 9- Spike Frequency Adaptation
➔ excitatory pyramidal cells→ have spike frequency adaptation currents→ hyperpolarizing currents,
activated when the membrane potential is high→ de-activated, slowly, when membrane is low
→ many neurons cannot rapid firing over a long time
➔ two kinds of adaptation currents, called M current and calcium-dependent
afterhyperpolarization (AHP) currents
➔ M-currents are active even before the neuron fires
➔ Calcium-dependent AHP currents are firing-activated

9.1 A Model M-Current

➔ M-current are depolarization-activated, slowly decaying, hyperpolarizing potassium currents
➔ Down-regulated by activation of the muscarinic acetylcholine receptors (M=muscarin)

➔ Im as a current density non a current

➔ at rest, the M-current→ gives rise to a weak but significant tonic (constant) potassium current.

9.2 Calcium-Dependent AHP Currents

➔ Calcium-dependent AHP currents→ are activated by influx of calcium that results from firing
➔ are therefore strictly spiking activated