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Neuroscience

Il existe un

vieux débat en
neurosciences
sur les
contributions
relatives du
thalamus et du
cortex dans le
processus qui
produit
l’activité
cérébrale
présente dans
le cortex
sensoriel
primaire
Les deux positions dans ce débat

 A un extrême se  A l’autre extrême


trouve un modèle se trouve le
de type « feed- point de vue
forward » où les selon lequel
connexions l’information
corticales venant du
locales ne jouent thalamus ne fait
pas un rôle que
dominant et perturberl’activi
l’activité est té spontanée déjà
dictée présente dans un
majoritairement réseau cortical
par les entrées fortement
thalamiques interconnecté.
(Hubel et Weisel). 
Les deux positions dans ce débat

Perceptron dépourvu d’activité Activité spontanée déjà présente


spontanée dans un réseau cortical fortement
interconnecté

Schematic diagram of circuitry for the lateral


geniculate nucleus. The inputs to relay cells
are shown along with the relevant
neurotransmitters and postsynaptic receptors
(ionotropic and metabotropic ) Abbreviations :
LGN, lateral geniculate nucleus ; BRF, brainstem
A Lejeune reticular formation; TRN, thalamic reticular 3
Les deux positions dans ce débat
étendu à l ’ ensemble des sciences
cognitives ( Varela , 1992 )
La position de la poule La position de l ’ oeuf

 Le monde  Le système
extérieur cognitif crée son
comporte des propre monde, et
règles fixes; il toute son
précède l’image apparente
qu’il projette sur solidité repose
le système sur les lois
cognitif dont la internes de
tâche est de l’organisme
saisir – le monde
– de manière
appropriée
A Lejeune (que 4
Somatosensory Corticothalamic
Projections: Distinguishing
Drivers from Modulators

par

Iva Reichova et S. Murray


Sherman
Journal of Neurophysiology, 2004

Présentation d’un article au


professeur Thomas Gisiger
dans le cadre du cours
Introduction
Rappel: les récepteurs ioniques et métabotropiques
Rappel: les effets inhibiteur ou exitant

The ion channel is regulated by a ligand and is usually very


selective to one or more ions likeNa+, K+, Ca2+ , or Cl-. Such
receptors located at synapses convert the chemical signal of
presynaptically released neurotransmitter directly and very
quickly into a postsynaptic electrical signal.
  In contrast to the latter ,
metabotropic receptors do not
form an  ion channel pore; rather ,
they are indirectly linked with
ion - channels on the plasma
membrane of the cell through 
signal transduction  mechanisms ,
often  G proteins. Hence , they are
a type of 
G protein - coupled receptor.
Others are  tyrosine kinases or 
guanylyl cyclase receptors
A Lejeune . 6
First transmission

Drivers et Modulators
to cortex from the
periphery
=DRIVER

L’aire corticale 1
étant une aire
sensorielle primaire, sa
couche 4
est la cible de

projections du noyau First (Reichova et Sherman, 2004)


sensoriel thalamique A transmission to
cortex from the
(le CGL par periphery=DRIV
exemple).
ER

Les aires corticales 1, (A)


2 et 3 sont aussi LGN : Lateral Geniculate Nucleus
reliées par des VP : Ventral Posterior Nucleus
projections
cortico-corticales

liant leurs couches 1-3 First


et 6. transmission to
Le noyau thalamique A
cortex from the
reçoit aussi des periphery =DRIVER
projections en retour
de l’aire
corticale 1, qui sont

issues de sa couche 6
Les inputs
cholinergiques Drivers et Modulators (
du niveau 5

Le noyau B représente


par exemple
une partie du

pulvinar.
Il ne reçoit aucune

information
DRIVER
sensorielle,
mais il est la cible

de
connexions projetées
(A) (B)
par
les neurones des

couches 4 et 5 de
l’aire corticale 1.
Il est aussi connecté

avec l’aire 2,
projetant sur sa
niveau 5 est

Drivers et Modulators (
limitée àla
morphologie
(Flowery) – Li et al.
(2003)
Le
 but de cette
recherche est
d ’ approfondir cette
hypothèse de Li et al .
( 2003 ) qui distinguent –
sur des bases
morphologiques – deux
groupes d ’ inputs sur le
Lateral Posterior
Thalamus ( LPT ):
- Un groupe avec
‘ synaptic depression ’
inhibiteur ;
- - un groupe avec
‘ synaptic
facilitation ’
stimulation … sans
toutefois identifier
On la va donc
source activer les axones des couches 5 et 6 sur une
corticale
couche( niveau 5 OU 6? )
thalamocorticale et enregistrer les réponses sur le
noyau ventral postérieur ( 1er ordre FO ) et le noyau médial

postérieur ( HO )
First-order relays represent the first transmission
Design de lato cortex of particular type of information from the periphe
recherche Higher-order relays serve to transmit information between
cortical areas via a cortico-thalamo-cortical route

comparaison avec

1st O HO

In v e s tig a te s y n a p tic p ro p e rtie s o f 8 cells


co rtico th a la m ic in p u ts
9 8 ce lls

Retinogeniculate activation evoked large, all-or-none excitatory postsynaptic potentials


(EPSPs) that showed paired-pulse depression antagonized by N-methyl-D-aspartate (NMDA)
and AMPA receptor blockers but with no sign of a metabotropic glutamate receptor (mGluR)
component.
Corticogeniculate activation evoked small, graded EPSPs showing paired-pulse

facilitation, and the EPSPs showed both NMDA and AMPA receptor component plus an
mGluR1 component
A Lejeune 10
methods

A Lejeune 11
FIG. 1. Mouse
thalamocortical
slice preparation
as
seen in recording
chamber
A: lower-power view of
slice. Barrel cortex (BC)

can be clearly identified


as
well as the external

and internal capsules


(EC, IC) and
the ventral posterior

(medial and lateral) and


posterior
medial nuclei (VP,

POm). The stimulating


electrode is
shown in the barrel

cortex and recording


electrodes are
located in the ventral

posterior and posterior


medial
A Lejeune 12
nuclei.
Stimulation and
recording (2)
Recordings from geniculate cells were

performed under visual control.


Electrical stimulation was performed in


the
optic tract, which lies ventral to the

lateral geniculate nucleus, and in the


optic radiations, which lie dorsal.

A Lejeune 13
Rappel: D e s a n ta g o n iste s so n t u tilisé s su r le s
A receptor ré ce p te u rs G A B A ( a e t b ),
antagonist is… A M PA , m G lu R , m G lu R 5

A receptor  1] In pharmacology
antagonist is a ,antagonists have affinity
type of receptor   but no efficacy for their
ligand or cognate receptors, and
 drug that does binding will disrupt the
not provoke a interaction and inhibit the
biological
function of an agonist or 
inverse agonist at receptors.
response itself Antagonists mediate their
upon binding to effects by binding to the
a receptor, but active site or to allosteric
blocks or sites on receptors, or they
dampens agonist may interact at unique
-mediated binding sites not normally
responses.[ A Lejeune
involved in the biological 14
Rappel:
A receptor
antagonist is…
(2)

. Antagonist activity
may be reversible or
irreversible
depending on the
longevity of the
antagonist–receptor
complex, which, in
turn, depends on the
nature of antagonist
receptor binding.
The majority of drug
antagonists achieve
their potency by
competing with
endogenous ligands
or substrates at
structurally-definedA Lejeune 15
Paired-pulse facilitation:
definition
 When a presynaptic neuron receives
two stimuli in rapid succession, the
postsynaptic response will commonly
be larger for the second than for the
first pulse — a phenomenon known as
paired-pulse facilitation (PPF). Now
here's an easy question for every
neurophysiologist: what is the
mechanism responsible for PPF?
Although most people will quickly
point in the direction of 'residual
A Lejeune 16
Paired-pulse depression

 When two depolarizing stimuli are


delivered in close succession to a
group of axons, their average
response to the second one is
sometimes smaller than to the
first. This form of short-term
plasticity is more common at
inhibitory than at excitatory
synapses.
A Lejeune 17
results
EPSPs showing the modulator signature :paired-pulse

facilitation, graded response, mGluR component ; the driver


signature : paired-pulse depression, all-or none response,
no mGluR component

A Lejeune 18
FIG. 1. Mouse
thalamocortical
slice preparation
as
seen in recording
chamber
A: lower-power view of
slice. Barrel cortex (BC)

can be clearly identified


as
well as the external

and internal capsules


(EC, IC) and
the ventral posterior

(medial and lateral) and


posterior
medial nuclei (VP,

POm). The stimulating


electrode is
shown in the barrel

cortex and recording


electrodes are
located in the ventral To iso la te excita to ry p o stsyn a p tic p o te n tia ls
posterior and posterior ( EPSPs ) in allrecordings , we used GABA receptor
medial a n ta g o n ists
A Lejeune 19
nuclei.
Synaptic inputs to cells of
the lateral geniculate
nucleus
W e th u s e le ctrica lly stim u la te d
th e o p tic tra ct a n d ra d ia tio n s w h ile
re co rd in g fro m
g e n icu la te re la y ce lls.

ra t: G ra n se th a n d Lin d stro ¨ m 2 0 0 3 ; Tu rn e r To h e lp e sta b lish syn a p tic p ro p e rtie s o f


a n d S a lt 1 9 9 8 ; m o u se : C h e n a n d R e g e h r d rive rs a n d co n tra st th e m w ith la ye r 6
2 0 0 0 ; C h e n e t a l. 2 0 0 2 ; g u in e a p ig :
M cC o rm ick a n d V o n K ro sig k 1 9 9 2 ; ca t: m o d u la to r p ro p e rtie s w ith o u r te ch n iq u e s, w e
Lin d stro ¨ m a n d W ro ´b e l1 9 9 0 ; a lso o u r o w n first re co rd e d fro m th e la te ra lg e n icu la te
u n p u b lish e d o b se rva tio n s
n u cle u s.
A Lejeune 20
FIG. 2. Drivers
and modulators in sh o w in g excita to ry p o stsyn a p tic p o te n tia ls
the mouse lateral ( EPSPs ) evoked from stimulation of
geniculate re tin o g e n icu la te a ffe re n ts via th e o p tic tra ct
nucleus ( Ai–Di) or corticogeniculate afferents via
the optic radiation (Aii–Dii)
In this and all subsequent
figures
showing evoked EPSPs,

inhibition was blocked by


application of SR95531 (a
GABAA antagonist, 20 M) and
CGP46381 (a GABAB
antagonist, 40 M).
 A, i and ii: large EPSP
showing paired-pulse
depression evoked
from retinogeniculate
stimulation (Ai)
contrasts with small
EPSP showing paired-
pulse facilitation
evoked from
corticogeniculate
stimulation (Aii).
A Lejeune 21
 B, i and ii: increasing
FIG. 2. Drivers
and modulators in sh o w in g excita to ry p o stsyn a p tic p o te n tia ls
the mouse lateral ( EPSPs ) evoked from stimulation of
geniculate re tin o g e n icu la te a ffe re n ts via th e o p tic tra ct
nucleus (Ai–Di) or corticogeniculate afferents via the
optic radiation (Aii–Dii)
 C, i and ii: EPSPs evoked
by low-frequency
stimulation (10 Hz) from
both sites completely
blocked by AMPA and N-
methyl-D-aspartate (NMDA)
receptor antagonists (DNQX,
50 M, and MK-801, 50 M,
respectively).
 D, i and ii: high-frequency
stimulation (HFS, 110 Hz)
of retinogeniculate
afferents evokes no
further response with
continued application of
AMPA and NMDA
antagonists (Di).
 Low-frequency stimulation
(LFS, 10 Hz) of
corticogeniculate afferents in
the presence of continued
AMPA and NMDA antagonists
A Lejeune 22
Synaptic inputs to cells of the
ventral posterior medial and
posterior medial nuclei
We focused on two thalamic relays.
One is the ventral posterior ( VP – 1 st order )
medial nucleus, which is a first order relay, like
the lateral geniculate nucleus, and thus receives
only a layer 6 input from cortex. The other is the
posterior medial ( POm – High Order ) nucleus,
which is mostly a higher-order relay, like the
pulvinar, and thus receives inputs from both layer 5
and layer 6 of cortex.

Corticothalamic connections in the slice


Synaptic properties of layer 6 inputs to
the ventral posterior medial nucleus ( VP –
1 st Order )
Cortical inputs to the posterior medial
A Lejeune 23
Corticothalamic
connections in the
slice
EPSPs showing the modulator signature :paired-pulse

facilitation, graded response, mGluR component ; the driver


signature : paired-pulse depression, all-or none response,
no mGluR component

A Lejeune 24
of the
corticothalamic C o rtico th a la m ic a xo n s fro m la ye rs 5
pathway a n d 6 a re o rth o g ra d e ly la b e le d b y
b io cytin io n to p h o re sis in to th e b a rre l
co rtex
A: injection site
(arrow) in BC.
Also visible is the
IC. The lettered
boxes refer to the
higher power views
in B–D.
B: labeled axons

running between
external and
internal capsules.
C: terminal

boutons of
cortical fibers in
thalamic reticular A Lejeune 25
corticothalamic C o rtico th a la m ic a xo n s fro m la ye rs 5
pathway
a n d 6 a re o rth o g ra d e ly la b e le d b y
b io cytin io n to p h o re sis in to th e b a rre l
co rtex
Many axons ramify in
the thalamic reticular
and ventral posterior
nuclei and terminate
there, but a few
continue further to the
posterior medial
nucleus.
D: terminal boutons

of cortical axons in
the ventral posterior
medial nucleus and
POm.
Several of the larger

boutons in the
posterior medial

nucleus are circled.


A Lejeune 26
layer 6 inputs to the
ventral posterior (VP – 1st
Order) medial nucleus
EPSPs showing the modulator signature :paired-pulse

facilitation, graded response, mGluR component ; the driver


signature : paired-pulse depression, all-or none response,
no mGluR component

A Lejeune 27
subcortical A : e x a m p le o f e v o k e d E P S P s.
stimulation in a cell B : p a ire d - p u lse fa cilita tio n a n d g ra d e d
in the ventral re sp o n se o f E P S P s
posterior medial C : e v id e n ce o f a n m G lu R 1 co m p o n e n t.
nucleus D : co n tro l. LY 3 6 7 3 8 5 ( 5 0 M ) a p p lie d to th e
ce ll d o e s n o t sh o w a n y e ffe ct o n its m e m b ra n e
 The EPSPs evoked p o te n tia l
by low frequency
stimulation (LFS 400 A,

14 Hz for 800 ms)


are blocked with

application of MK-801
and DNQX
(top). With these

antagonists present,
high-frequency
stimulation (HFS, 125

Hz for 800 ms) evoked


a sustained
EPSP (middle) that is

blocked by the mGluR1


antagonist, LY367385

(50 M, bottom).
The line below the

trace marks the time of


A Lejeune 28
the drug application.
Cortical inputs to the
posterior medial (POm
HO) nucleus
EPSPs showing the modulator signature :paired-pulse

facilitation, graded response, mGluR component ; the driver


signature : paired-pulse depression, all-or none response,
no mGluR component

A Lejeune 29
EPSPs evoked from
stimulation of layer A : e xa m p le o f e vo ke d E P S Ps
6 of barrel cortex in B : p a ire d - p u lse fa cilita tio n a n d g ra d e d
a cell of the
posterior medial re sp o n se o f E P S Ps
nucleus C : e vid e n ce o f a n m G lu R 1 co m p o n e n t
The EPSPs
evoked by LFS (13 Hz

for 600 ms; for all


traces, stimulation

intensity was 150 A) are


blocked with application

of MK-801 and
DNQX (top). With these

antagonists present,
HFS (125 Hz for 600 ms)

evoked a sustained
EPSP (2nd trace) that is

not blocked by MPEP,


an mGluR5 antagonist

(30 M, 3rd trace) but


is blocked by LY367385,

an mGluR1 antagonist
(50 M, bottom).

A Lejeune 30
stimulation of layer A : e x a m p le o f e v o k e d E P S P s
5 of barrel cortex in B : p a ire d - p u lse d e p re ssio n
a cell of the C : a ll- o r- n o n e re sp o n se o f E P S P s is a p p a re n t
posterior medial fro m re sp o n se s to in cre a sin g stim u la tio n
nucleus in te n sitie s
D : la ck o f m G lu R co m p o n e n t
After
blocking
EPSPs with
DNQX
and MK-801,

neither LFS
(50 Hz for
855 ms, top)
nor HFS
(125 Hz for

855 ms,
bottom)
A Lejeune 31
of graded and all-
or-none EPSPs
from cells of the
posterior medial
nucleus

The 3
examples of
all-or-none
responses (—
and ) reflect
stimulation
from layer 5,
whereas the 5
examples of
graded
responses
(- - - and )
A Lejeune 32
EPSPs evoked from
separate stimulation of
layers 5 and 6 of barrel
cortex in the same cell
of the posterior medial
nucleus
A, i and ii: paired-
pulse effects, showing
depression for layer 5
stimulation (Ai) and
facilitation for layer 6
stimulation (Aii).
B, i and ii:

recruitment
properties, showing all-
or-none response for
layer 5 stimulation (Bi)
and graded responses
for layer 6 stimulation
A Lejeune 33
EPSPs evoked from
separate stimulation of
layers 5 and 6 of barrel
cortex in the same
cellof the posterior
medial nucleus
C, i and ii:
contribution of
mGluRs. Application of
DNQX and MK-801
blocks EPSPs to LFS (9
Hz for 755 ms) both
from layer 5 (Ci, top)
and
from layer 6 (Cii, top).

HFS (125 Hz for 755 ms)


evokes nothing further
from layer 5 (Ci, bottom)
but evokes a
prolonged EPSP from

layer 6 (Cii, middle), and


A Lejeune 34
discussion
EPSPs showing the modulator signature :paired-pulse

facilitation, graded response, mGluR component ; the driver


signature : paired-pulse depression, all-or none response,
no mGluR component

A Lejeune 35
cortico-thalamo-
cortical
communication
involving
higher-order
thalamic relays.
This hypothesis suggests
that information arrives
initially at the cortical
level after transmission
through a 1rst-order (FO)
thalamic relay such as the
lateral geniculate nucleus,
ventral division of the
medial geniculate nucleus
(MGNv), or medial or
lateral VP. Further
corticocortical
communication in addition

to or perhaps instead of
direct pathways
involves transmission via

higher-order (HO)
thalamic relays, such as
the pulvinar (Pul),
magnocellular division of
the medial geniculate
nucleus or the POm. A
remaining issue is the
identity of direct
corticocortical pathways A Lejeune 36
Discussion
T h is h y p o th e sis su g g e sts th a t in fo rm a tio n
a rriv e s in itia lly a t th e co rtica l le v e l a fte r
tra n sm issio n th ro u g h a 1 rst- o rd e r ( F O )
th a la m ic re la y su ch a s th e la te ra l g e n icu la te
n u cle u s , v e n tra l d iv isio n o f th e m e d ia l
g e n icu la te n u cle u s ( M G N v ) , o r m e d ia l o r
la te ra l V P .
F u rth e r co rtico co rtica l co m m u n ica tio n in
a d d itio n to o r p e rh a p s in ste a d o f d ire ct
p a th w a y s in v o lv e s tra n sm issio n v ia h ig h e r-
o rd e r ( H O ) th a la m ic re la y s , su ch a s th e
p u lv in a r ( P u l) , m a g n o ce llu la r d iv isio n o f th e
m e d ia l g e n icu la te n u cle u s o r th e P O m .
A re m a in in g issu e is th e id e n tity o f d ire ct
co rtico co rtica l p a th w a y s a s d riv e r o r
A Lejeune 37
Une image
vaut mille
mots…

Review
Thalamic Relay Functions
and Their Role in
Corticocortical
Communication:
Generalizations from the
Visual System
R.W. Guillery1 and

S.Murray Sherman2, ,
1Department of Anatomy,

University of Wisconsin
School of Medicine, 1300
University Avenue,
Madison, WI 53706 USA
2
Department of
Neurobiology, State
University of New York,
Stony Brook, NY 11794
USA

Available online 22
January 2002.
 A Lejeune 38
Questions
??

Somatosensory

Corticothalamic
Projections:
Distinguishing
Drivers from
Modulators

 par

Iva Reichova et

S. Murray
Sherman
Journal of

Neurophysiolog
y, 2004

A Lejeune 39