5.

How is the communication between brain cells

modified by previous activity (experience)?

Mechanisms of short-term
synaptic plasticity
(with emphasis on the diversity of synaptic plasticity
mechanisms at different synapses)
In general (but not always) synapses with high probability of release (e.g. cerebellar CF-PC
synapses) depress during repetitive activity, while synapses with low probability of release
(e.g. cerebellar PF-PC synapses) facilitate during repetitive activity.

Synapses with
intermediate probability of
release (e.g. hippocampal
Ca3-CA1 synapses) may
first facilitate and then
depress during repetitive
activity.

Atwood and Karunanithi (2002) Nature

Rev. Neurosci. (2002) 3 497
Even synapses formed by the same presynaptic neuron on different
postsynaptic neurons can have different STP properties
(e.g. cf synapses between cortical L2/3 pyramidal neurons and FS interneurons or
SOM interneurons)

- Target cell-dependent STP properties

Due to feedback modulation by postsynaptic neuron
The synapse between layer 2/3 pyramidal cells and FS interneurons show short-term
depression during 10 Hz AP trains in wild-type (WT) mice.

The short-term depression at this synapse is enhanced in knockin mouse models of migraine
(FHM1 KI), which carry a gain-of-fnction mutation in the CaV2.1 channel that increases the
probability of glutamate release (cf two times larger EPSP at the 1° pulse in the train)

PYR FS

WT

FHM1 KI
WT (n=16)
FHM1 KI (n=17)

WT FHM1

Tottene et al, 2009 Neuron

 The synapse between layer 2/3 pyramidal cells and SOM interneurons show short-term
facilitation during 25 Hz AP trains in wild-type (WT) mice.

The short-term facilitation is unaltered at this synapse in knockin mouse models of

migraine (FHM1 KI), which carry a gain-of-fnction mutation in the CaV2.1 channel that
increases the probability of glutamate release (cf about two times larger EPSP at the 1°
pulse in the train and also subsequent pulses)

25 10 EPSP5/EPSP1
25 Hz
20 8
EPSPi / EPSP1

EPSPi / EPSP1
15 6
PYR SOM+
EPSP2/EPSP1
10 4

5 2

0.2 mV 50 ms 15 18 15 18
0 0
WT FHM1 WT FHM1

Pilati, Forli et al.

The synapse between thalamocortical relay neurons and L4 principal excitatory (RS)
neurons show short-term depression during 10 Hz AP trains in wild-type (WT) mice.

The short-term depression is enhanced at this synapse in knockin mouse models of

migraine (FHM1 KI), which carry a gain-of-function mutation in the CaV2.1 channel that
increases the probability of glutamate release (cf about two times larger EPSC at the 1°
pulse in the train)

WT
300 1,0
FHM1
*
250
0,8

normalized EPSC
EPSC (pA)

*
-83 mV 200
File:RS_traccia_media_5P10Hz.opj **
27/02/2019 11:55:54

0,6 *
*
150
50 pA
0,4
50 ms
100

0,2
50
50 pA
50 ms

0 0,0
1 2 3 4 5 1 2 3 4 5
Stimulus number Stimulus number

1,0
600
Tottene et al. 2019, J Neurosci
500 0,8
The synapse between thalamocortical relay neurons and L4 fast-spiking (FS) interneurons
show short-term depression during 10 Hz AP trains in wild-type (WT) mice.

The short-term depression is unaltered at this synapse in knockin mouse models of

migraine (FHM1 KI), which carry a gain-of-function mutation in the CaV2.1 channel that
increases the probability of glutamate release (cf larger EPSC at the 1° pulse in the train)

VC

WT
1800 1.0
FHM1
1600

Erev 1800 0.8 1.0

normalized EPSC
1400
IPSC
(pA) (pA)

1600
1200
* 0.8

normalized EPSC
1400 0.6
EPSC

1000
1200
800 0.6
EPSC

1000 0.4
600
800
0.4
400
600
0.2
400
200 0.2

200
0 0.0
STIM 0 1 2 3 4 5 1 0.0 2 3 4 5
1 Stimulus
2 number
3 4 5 Stimulus
1 number
2 3 4 5
Stimulus number Stimulus number

200 pA
50 ms
200 pA

 Postsynaptic target cell-dependent short-term plasticity

50 ms

at thalamocortical synapses
20 mV
As a consequence of synaptic plasticity, the effect of an AP in
a presynaptic neuron on the activity of the postsynaptic
neuron can greatly vary depending on the previous sequence
of presynaptic APs.
 Irregular train of presynaptic APs (average frequency 20 Hz)
to simulate physiological activity
EPSC10/EPSC1 as a function of the
AP frequency in a regular

Low-pass filter
EPSC

High
Prelease
High-pass filter

Low
Prelease
Band-pass filter

Intermediate
Prelease

NB Neuromodulators modulate short-term synaptic plasticity!

Neuromodulators modulate short-term synaptic plasticity
and thus modulate the information processing by neural
circuits
Neuromodulators modulate short-term synaptic plasticity
and thus modulate the information processing by neural
circuits

Mutations causing neurological diseases may alter

short-term synaptic plasticity and thus alter information
processing by neural circuits
The computations taking place in the cerebral cortex depend on highly interconnected
and dynamic microcircuits composed of two broad types of neurons: (1) glutamatergic
excitatory neurons, or principal cells (PCs) (2) GABAergic inhibitory interneurons (INs).

Three main cortical microcircuits core motifs involving inhibitory interneurons

Feedback Feedforward
Disinhibition
inhibition inhibition

˗ ˗

+
Recurrent Lateral

˗
inhibition
˗
inhibition ˗

+
+ + +

Tremblay et al (2016) Neuron

 Three main cortical microcircuits core motifs involving inhibitory interneurons

Feedback Feedforward Dishinhibition

inhibition inhibition

˗ ˗

+
Recurrent Lateral

˗
inhibition
˗
inhibition ˗

+
+ + +

PV, SOM PV VIP----SOM (L2/3, L5)

SOM---PV (L4)

--Essential for the correct processing of sensory information

(e.g. gain control and dynamic range modulation, sensory feature selectivity, surround
suppression, synchronization, cell assemblies formation and competition)

--Essential to maintain a dynamic cellular excitatory-inhibitory (E/I)

balance necessary for the transfer of information while preventing runaway
excitation
Tremblay et al (2016) Neuron