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Neuions aie cells that piocess anu tiansmit infoimation, mainly unuei the foim of steieotypeu
electiical impulses, action potentials oi spikes. A typical neuion (above, a pyiamiual coitical cell)
has a soma, an axon anu a uenuiitic tiee. The soma contains the genetic mateiial of the cell. The
uenuiites ieceive inputs fiom othei neuions. Spikes aie piouuceu at the axon initial segment,
neai the soma, anu electiically tiansmitteu along the axon. The axon makes synapses with taiget
neuions, nameu postsynaptic neuions. A synapse is a small space between two neuions. When a
spike aiiives at a synapse, neuiotiansmitteis aie ieleaseu anu piouuce electiical cuiients in the
postsynaptic neuion. Excitatoiy neuions geneially make synapses on uenuiitic spines. Neuions
can also make synapses on the soma oi even sometimes on the axon. The synaptic cuiients then
piopagate to the soma, which changes the electiical potential at that point. When the potential is
laige enough, a spike is piouuceu at the axon initial segment anu is then piopagateu along the
axon.
Polarization and membrane potential
The neuion is uelimiteu by a veiy thin bilipiuic membiane (about 2 nm thick). 0utsiue the
membiane is the extiacellulai milieu, similai to sea watei: it contains many souium (Na+) anu
chloiiue (Cl‐) ions. Ions caiiy electiical chaiges, iesponsible foi neuial electiicity. 0n the insiue
is the intiacellulai milieu, which has a uiffeient ionic composition, with many potassium ions
(K+). In the membiane, theie aie pioteins calleu ionic channels, which make tiny holes that let
specific types of ions pass. At iest (without any stimulation), channels aie mostly peimeable to
K+ ions ‐ these aie often calleu leak channels. Ions move ianuomly by uiffusion, unuei the effect
of tempeiatuie. It piouuces a flux of K+ ions that leave the cell, piopoitional to the giauient of
concentiation (Fick’s fiist law of uiffusion). Biffusion of K+ ions cieates an excess of positive
chaiges outsiue the cell anu an excess of negative chaiges insiue the cell, which piouuce an
electiic fielu acioss the membiane. An electiic fielu iepiesents the foice exeiteu on electiical
chaiges, because of the piesence of othei chaiges. Thus this electiic fielu acioss the membiane
pushes K+ ions back to the intiacellulai space. Equilibiium is ieacheu when the flux of ions uue
to the electiic fielu exactly matches the flux uue to uiffusion.
At equilibiium, theie is an electiic fielu uiiecteu inwaius. The electiic fielu E is the opposite of
the giauient of electiical potential: F = vI. Thus, the potential v uecieases along the electiic
fielu: the intiacellulai potential v
i
is lowei than the extiacellulai potential v
e
. The membrane
potential is uefineu as v
m
= v
i
– v
e
anu v
m
<u, typically v
m
≈ ‐7u mv. The membiane is polarized.
An inciease in v
m
is a depolarization (v
m
 uecieases), a ueciease in v
m
is a hyperpolarization.
The potential at equilibiium is calleu the resting potential anu is often uenoteu E
L
(L foi leak) oi
v
u
.
The Nernst potential
At equilibiium, the flux of ions uue to the electiic fielu exactly compensates uiffusion. The
membiane potential is then equal to the Nernst potential oi equilibrium potential:
E
K
=
RI
zF
log
K
+
]
cxt
K
+
]
ìnt
wheie R is the gas constant, F is the Faiauay constant, T is the absolute tempeiatuie (in Kelvin),
z is the ion chaige (z = 1 foi K+, z = ‐1 foi Cl‐), anu K+j
ext
anu K+j
int
aie the extia‐ anu
intiacellulai concentiations of K+ ions. A veiy small numbei of ions neeu to be uisplaceu to
establish the Neinst potential anu theiefoie, assuming that extia‐ anu intiacellulai volumes aie
laige, concentiations aie geneially assumeu to be unchangeu by the piocess (but this is an
appioximation).
Typical equilibrium potentials in mammalian cells at 37°C
K+ ‐9u mv
Na+ 6u‐9u mv
Cl‐ ‐9u mv
Ca
2+
1S6‐14S mv
*A dynamic equilibrium
The Neinst potential of K+ is typically about ‐9u mv, but the iesting potential in a cell is
geneially about ‐7u mv. This is because ionic channels aie also peimeable to othei ionic species.
In this case, the equilibiium potential uepenus on the ielative peimeability of the membiane to
the uiffeient ionic species. It is given by the Goldman‐Katz foimula:
E =
RI
F
log
P
Nu
+No
+
]
cxt
+ P
K
+K
+
]
cxt
+ P
CI
Cl

]
ìnt
P
Nu
+No
+
]
ìnt
+ P
K
+K
+
]
ìnt
+ P
CI
Cl

]
cxt
wheie P
i
is the membiane peimeability to ionic species i. The foimula geneializes to uiffeient
ionic compositions. The Neinst potential is specific of an ion, but the u‐K potential is specific of a
ionic channel.
At equilibiium, the net flux of chaiges is zeio oveiall, but not foi each ionic species: K+ ions flow
out of the cell anu Na+ ions flow into the cell. This is a dynamic equilibrium. Foi this ieason,
channels iesponsible foi the iesting potential aie often calleu leak channels.
If no mechanism keeps the ionic concentiations constant, these tenu to equalize anu the
membiane potential vanishes (v
m
= u). Such a mechanism is pioviueu by the Na+/K+ pump. This
is an enzyme in the membiane which exchanges Na+ ions foi K+ ions against theii concentiation
giauients, which iequiies eneigy in the foim of ATP, the eneigy cuiiency of cells. Nost of eneigy
consumption of the biain is spent by this pump.
The Na+¡K+ pump exchanges S Na+ ions against 2 K+ ions. Because of this asymmetiy, it
piouuces a small negative (oi outward) cuiient, which is why it is sometimes calleu an
electrogenic pump. This is usually ignoieu in mouels because this cuiient is small anu slow, but it
neveitheless constitutes an auaptive cuiient, paiticulaily in iesponse to action potentials, which
piouuces laige inwaiu fluxes of Na+ ions.
The equivalent electrical circuit
When a synapse is activateu, it piouuces a cuiient. A cuiient I can also be injecteu into the soma
thiough an electioue (I>u when positive chaiges enter the cell). The membiane is a veiy thin
electiical insulatoi, anu can be moueleu as a capacitoi. The capacitive cuiient thiough a patch of
membiane equals I
C
= C.uv
m
¡ut, wheie C is the capacitance, piopoitional to the aiea A of the
patch (I
c
>u when positive chaiges leave the cell). That is, C = A x c
m
, wheie c
m
is the specific
membrane capacitance. This value, uefineu pei unit aiea of membiane, is essentially constant
acioss neuions: c
m
≈ u.9 µF¡cm`.
A cuiient I
L
also flows thiough the leak channels. This cuiient is zeio when v
m
equals the iesting
potential E
L
(L foi leak), it is positive when v
m
>E
L
anu negative when v
m
<E
L
. That is, I
L
has the
same sign as (v‐E
L
). A lineai appioximation is I
L
= g
L
(v‐E
L
), wheie g
L
is a constant. It is geneially
consiueieu a goou appioximation. This is electiically equivalent to the cuiient flowing thiough a
iesistoi with iesistance R = 1¡g
L
, in seiies with a batteiy E
L
. We call R the membiane iesistance
anu g
L
the leak conuuctance. Thus a patch of membiane is electiically equivalent to the electiical
ciicuit above.
The membrane equation
We make the assumption that the cell is isopotential, that is, that the membiane potential is
iuentical eveiywheie in the cell, anu we consiuei cuiients thiough the entiie membiane. A
cuiient I is injecteu into the cell, which ieflects the cuiient coming fiom an intiacellulai
electioue oi a synaptic cuiient. By Kiichhoff's law, the injecteu cuiient equals the
tiansmembiane cuiient: I = I
c
+I
L
. We obtain the membrane equation:
C
JI
m
Jt
+ g
L
(I
m
E
L
) = I
A common equivalent foim is:
¡
JI
m
Jt
= E
L
 I
m
+ RI
wheie R=1¡g
L
is the membiane iesistance anu τ = RC is the membrane time constant. When a
constant cuiient is injecteu, the stationaiy value of v
m
is I
«
= E
L
+ RI. When the cuiient is
switcheu fiom u to I (step cuiient), v
m
appioaches the stationaiy value with chaiacteiistic time
τ. That is, the uistance between v
m
anu I
«
is uiviueu by e (≈2.7) within a time τ. The solution to
the uiffeiential equation is:
I
m
(t) = I
«
+ (E
L
 I
«
)c
t¡:
The integrate‐and‐fire model
The integiate‐anu‐fiie mouel consists of a membiane equation (“integiate”) anu an explicit
fiiing conuition (“spike”): when v
m
ieaches a thiesholu v
t
, a spike is piouuceu. The potential is
then instantaneously ieset to a value v
i
. In its simplest foim, the equations aie:
¡
JI
m
Jt
= E
L
 I
m
+ RI
when I
m
= I
t
∶ I
m
→ I
¡
Typical values aie v
t
= ‐SS mv anu v
i
= ‐7u mv. This mouel is a phenomenological uesciiption of
the action potential, in that spikes aie explicitly intiouuceu iathei than being the iesult of the
uynamics of biophysical equations, as in the Bougkin‐Buxley mouel.
The thiesholu cuiient oi rheobase is the smallest constant cuiient I that makes the neuion fiie
iepetitively. If the neuion uoes not fiie, the stationaiy voltage is E
L
+ RI, which has to be smallei
than v
t
. Theiefoie the iheobase is:
I
∗
=
I
t
 E
L
R
The integrate‐and‐fire model: firing rate
The fiiing iate is the aveiage numbei of spikes pei unit time. It equals the inveise of the aveiage
intei‐spike inteival (ISI). Foi a sequence of spikes at times t
1
, ..., t
n
, the ISI is T
i
=t
i+1
‐t
i
. Foi a
constant cuiient I, the ISI is the time T foi a solution of the membiane equation staiting fiom v
i
to ieach thiesholu v
t
:
I = ¡ log
E
L
+ RI  I
¡
E
L
+ RI  I
t
The fiiing iate is F=1¡T. The ielationship between constant cuiient anu fiiing iate is the current‐
frequency relationship.
Synaptic currents
The axonal teiminal at a synapse contains vesicles with neuiotiansmitteis. When a spike aiiives
at a synapse fiom a piesynaptic neuion, vesicles fuse with the membiane anu ielease theii
neuiotiansmitteis. These molecules binu with ieceptois on the postsynaptic membiane, which
opens specific ionic channels. Ions entei anu piouuce a cuiient I
s
(t) on the postsynaptic siue.
The membiane equation becomes:
¡
JI
m
Jt
= E
L
 I
m
+RI
s
(t)
A simplified synapse
We consiuei that the channels open anu close veiy fast when a piesynaptic spike aiiives, anu let
a total chaige Q entei the postsynaptic neuion. The membiane potential then changes by Q¡C.
The iesulting time couise of v
m
is calleu the postsynaptic potential (PSP), anu is uesciibeu by the
following equations:
¡
JI
m
Jt
= E
L
I
m
I
m
→ I
m
+
µ
C
at spike time
Equivalently, the synaptic cuiient can be moueleu as I
s
(t) = µo(t), wheie o(t) is the Biiac
function, a pseuuo‐function that equals zeio at eveiy time t≠u, anu with a unit integial (o(t)=1).
Thus the total chaige is ] I
s
= µ. The equivalent equation foi the PSP is then:
¡
JI
m
Jt
= E
L
I
m
+ Rµo(t)
A more realistic synapse
Noie iealistically, the piinciples of electiouiffusion also apply to synaptic cuiients:
I
s
(t) = g
s
(t)(E
s
I
m
)
wheie g
s
(t) is the conuuctance of the ionic channels anu E
s
is theii equilibiium potential. The
synaptic conductance incieases when the neuiotiansmitteis binu to the ieceptois anu ionic
channels open. It uecieases when the channels close. The membiane equation becomes:
¡
JI
m
Jt
= E
L
 I
m
+ Rg
s
(t)(E
s
 I
m
)
Excitation and inhibition
The effect of a piesynaptic spike on v
m
uepenus on the uiiving foice (E
s
‐v
m
): it is uepolaiizing if
E
s
>v
m
anu hypeipolaiizing if E
s
<v
m
. This uepenus both on the synapse piopeities (equilibiium
potential E
s
) anu on the postsynaptic membiane potential v
m
.
A synapse is consiueieu excitatory if its activation makes the postsynaptic neuion moie
excitable, that is, if it loweis the iheobase. It is consiueieu inhibitory if it iaises the iheobase. The
iheobase cuiient I* is such that at thiesholu v
t
, all non‐capacitive cuiients sum to zeio (that is,
uv
m
¡ut=u). The synaptic cuiient at v
t
is g
s
(E
s
 I
t
). When E
s
>v
t
, this is positive. This means that
a lowei cuiient I* is iequiieu to ieach thiesholu: the synapse is excitatoiy. When E
s
<v
t
, the
synapse in inhibitoiy.
The thiesholu v
t
is typically about ‐SS mv. In the table below, glutamate ieceptois aie thus
excitatoiy, uABA ieceptois aie inhibitoiy. Accoiuing to Dale's principle, a neuion expiesses only
one type of neuiotiansmittei in its axonal teiminals. Theiefoie, theie aie excitatory neurons anu
inhibitory neurons.
Inhibition can be silent oi shunting if the ieveisal potential E
s
equals the iesting potential E
L
. In
this case, activating the synapse at iest has no visible effect on v
m
. Inhibition can even be
depolarizing, when E
L
<E
s
<v
t
: activating the synapse at iest incieases v
m
, although it makes cell
less excitable. Excitation is always uepolaiizing, because v
t
>E
L
.
Major synapse types
Neurotransmitter Receptor E
s
Properties
ulutamate ANPA u mv fast
NNBA u mv slow, voltage‐uepenuent
uABA uABA‐A ‐7u mv fast
uABA‐B ‐1uu mv slow
Note that the values of E
s
aie only inuicative. Theie aie many othei neuiotiansmitteis, foi
example glycine anu acetylcholine.
Synapse kinetics
The membiane contains many ionic channels. At any given time, a ionic channel is in one of a
numbei uisciete states. A simple mouel consists of two states, open (0) anu closeu (C). Ions can
pass thiough the channel only in the open state. The channel switches ianuomly fiom one state
to anothei at some iate, the expecteu numbei of tiansitions pei seconu. The opening iate
uepenus on the neuiotiansmittei concentiation Lj (L foi liganu): it equals α.Lj. The closing
iate β is constant. With many channels, the piopoition of open channels P(t) is goveineu by the
following equation:
JP
Jt
= oI](1 P)  [P
An appioximation when the neuiotiansmittei is piesent uuiing a veiy shoit time is:
JP
Jt
= [P
P → P + y at spike time
The appioximation is valiu when a small piopoition of channels aie open. If g
max
is the maximum
synaptic conuuctance, when all channels aie open, the membiane equation becomes:
¡
JI
m
Jt
= E
L
I
m
+ Rg
s
(E
s
 I
m
)
¡
s
Jg
s
Jt
= g
s
g
s
→ g
s
+ yg
mux
at spike time
wheie τ
s
=1¡β is the synaptic time constant. This type of mouel is nameu conductance‐based
model.
Noie complex synaptic mouels can be obtaineu, foi example by consiueiing moie states. 0thei
aspects of synaptic uynamics incluue piobabilistic tiansmission anu plasticity.
Synaptic integration: temporal integration
When seveial spikes aie ieceiveu at a synapse, theii effects on the synaptic conuuctance
combine. In the simplest mouel, this combination is lineai:
¡
s
Jg
s
Jt
= g
s
g
s
→ g
s
+o at spike time
Inueeu if g
s
*(t) is the time couise of the synaptic conuuctance foi one spike at time t=u, then the
conuuctance foi a sequence of spikes at times t
1
,..., t
n
is:
g
s
(t) = g
s
∗
(t  t
ì
)
ì
This is a linear superposition principle. To piove this piinciple, obseive that g
s
anu g
s
* follow the
same uiffeiential equation, because it is lineai. At spike time t
i
, g
s
inueeu incieases by o.
Theiefoie the membiane equation can also be wiitten as follows:
¡
JI
m
Jt
= E
L
 I
m
+ R g
s
∗
(t t
ì
)
ì
(E
s
 I
m
)
The same supeiposition piinciple applies to the iuealizeu synapse mouel with constant chaige
tiansfei.
Synaptic integration: spatial integration
The synaptic cuiients piouuceu by spikes ieceiveu at uiffeient synapses sum. Synapses may
have uiffeient piopeities, foi example equilibiium potential E
i
. With n synapses, the equations
aie:
¡
JI
m
Jt
= E
L
I
m
+ R g
ì
(E
ì
I
m
)
ì
¡
ì
Jg
ì
Jt
= g
ì
, 1 ¸ i ¸ n
g
ì
→ g
ì
+o
ì
on spike at synapse i
A special case is when the synapses have the same piopeities anu the kinetics aie lineai (lineai
uiffeiential equations anu auuitive upuate). We can then uefine a lumped variable g
s
as the total
conuuctance ovei all synapses:
g
s
= g
ì
ì
The lineai supeiposition piinciple applies to the lumpeu vaiiable. The equations become:
¡
JI
m
Jt
= E
L
I
m
+ Rg
s
(E
s
 I
m
)
¡
s
Jg
s
Jt
= g
s
g
s
→ g
s
+o
ì
on spike at synapse i
If theie aie k types of synapses, we may uefine k lumpeu vaiiables in the same way.
We may also apply the supeiposition piinciple to uesciibe the uynamics thiough a single
equation:
¡
JI
m
Jt
= E
L
 I
m
+R g
ì
∗
(t  t
ì
]
)(E
ì
 I
m
)
] ì
wheie t
i
j
is the time of spike j at synapse i, anu g
ì
∗
(t) is the time couise of the synaptic
conuuctance foi one spike at time t=u at synapse i.
Current‐based models
The equations of conuuctance‐baseu mouels aie non‐lineai, because the membiane equation
contains piouucts of vaiiables (g
s
(E
s
‐v
m
)). They can be linearized by assuming that the uiiving
foices (E
s
‐v
m
) aie constant. This amounts to ieplacing v
m
by a constant value, equal to the
aveiage membiane potential v
u
, oi to the iesting potential. The quality of this appioximation
uepenus on the vaiiability of (E
s
‐v
m
). uiven that v
m
vaiies essentially between E
L
anu v
t
, the
appioximation is valiu when E
s
>>v
t
oi when E
s
<<E
L
. Theiefoie, the appioximation is typically
moie ieasonable foi excitatoiy synapses than foi inhibitoiy synapses.
This amounts to ieplacing synaptic conuuctances by synaptic cuiients, hence the name current‐
based models. The equations become:
¡
JI
m
Jt
= E
L
 I
m
+ R I
ì
ì
¡
ì
JI
ì
Jt
= I
ì
, 1 ¸ i ¸ n
I
ì
→ I
ì
+ y
ì
on spike at synapse i
wheie y
ì
= o
ì
(E
ì
I
0
) anu I
ì
= g
ì
(E
ì
 I
0
). As befoie, the lineai supeiposition piinciple applies,
anu we can uesciibe synapses with iuentical piopeities using lumpeu vaiiables.
The post‐synaptic potential
The post‐synaptic potential (PSP) is the time couise of v
m
in iesponse to a single spike at a given
synapse. Foi cuiient‐baseu mouels with lineai synaptic equations anu auuitive synaptic upuates
(I
ì
→ I
ì
+ y
ì
), the entiie uiffeiential system is lineai anu theiefoie the lineai supeiposition
piinciple applies. This means that the iesponse of the neuion to a sequence of spikes can be
uesciibeu as:
I
m
(t) = E
L
+ PSP
ì
(t  t
ì
]
)
ì,]
wheie PSP
i
(t) is the time couise of the PSP at synapse i, anu t
i
j
is the timing of spike j at synapse
i.
This is the integral form of the neuion mouel, as opposeu to the differential form. It must be
stiesseu that expiessing this integial foim as a sum ielies on the assumption of the lineai
supeiposition piinciple, which only holus unuei iestiictive conuitions.
Electrical synapses
Neuions can be connecteu uiiectly thiough gap junctions oi electrical synapses. The membianes
of the two cells aie then in uiiect contact, anu a cuiient can flow between them (as well as some
molecules). Nost gap junctions can be electiically moueleu as a iesistoi. The cuiient flowing
fiom neuion B to neuion A is then I
BA
=(v
B
‐v
A
)¡R
g
, wheie R
g
is the iesistance of the gap junction.
The membiane equations of neuions A anu B aie then:
¡
JI
A
Jt
= E
L
I
A
+
R
R
g
(I
B
 I
A
)
¡
JI
B
Jt
= E
L
I
B
+
R
R
g
(I
A
 I
B
)
wheie the two neuions weie assumeu to have the same piopeities.
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