Neuroscience s

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 trouve un modèle de type « feedforward » où les connexions corticales locales ne jouent pas un rôle dominant et l’activité est dictée majoritairement par les entrées thalamiques (Hubel et Weisel).

A l’autre extrême se trouve le point de vue selon lequel l’information venant du thalamus ne fait que perturberl’activi té spontanée déjà présente dans un réseau cortical fortement interconnecté.

Les deux positions dans ce débat
Perceptron dépourvu d’activité spontanée Activité spontanée déjà présente dans un réseau cortical fortement interconnecté

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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 3 reticular formation; TRN, thalamic reticular

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 extérieur comporte des règles fixes; il précède l’image qu’il projette sur le système cognitif dont la tâche est de saisir – le monde – de manière A Lejeune appropriée (que

Le système cognitif crée son propre monde, et toute son apparente solidité repose sur les lois internes de l’organisme
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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  A Lejeune guanylyl cyclase receptors .

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First transmission 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 sensoriel thalamique A (le CGL par exemple).
  

Drivers et Modulators

First transmission to cortex from the periphery=DRIV ER

(Reichova et Sherman, 2004)

(A) Les aires corticales 1, 2 et 3 sont aussi LGN : Lateral Geniculate Nucleus VP : Ventral Posterior Nucleus reliées par des projections cortico-corticales First liant leurs couches 1-3 transmission to et 6. cortex from the Le noyau thalamique A periphery =DRIVER reçoit aussi des projections en retour de l’aire corticale 1, qui sont issues de sa couche 6

Les inputs cholinergiques du niveau 5

Drivers et Modulators (

Le noyau B représente par exemple une partie du pulvinar. Il ne reçoit aucune information sensorielle, mais il est la cible de connexions projetées par les neurones des couches 4 et 5 de l’aire corticale 1. Il est aussi connecté avec l’aire 2, projetant sur sa

DRIVER

(A)

(B)

niveau 5 est limitée àla morphologie (Flowery) – Li et al. (2003)

Drivers et Modulators (

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 ): groupe avec - Un ‘ synaptic depression ’ inhibiteur ; un groupe avec - ‘ synaptic facilitation ’ stimulation … sans toutefois identifier On la donc activer les axones des couches 5 et 6 sur une va source corticale ( niveau 5 OU 6? ) couche thalamocorticale et enregistrer les réponses sur le

noyau ventral postérieur ( 1er ordre FO ) et le noyau médial postérieur ( HO )

Design de recherche

First-order relays represent the first transmission to la cortex of particular type of information from the periphe Higher-order relays serve to transmit information between cortical areas via a cortico-thalamo-cortical route

comparaison avec 1st O HO
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In v e s tig a te s y n a p tic p ro p e rtie s o f 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
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methods

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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 nuclei.

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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.

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Rappel: A receptor antagonist is…

D e s a n ta g o n i s so n t u ti i s su r l s ste l sé e ré ce p te u rs G A B A ( a e t b ), A M PA , m G l R , m G l R 5 u u
1] In pharmacology

A receptor  antagonist is a type of receptor  ligand or  drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist -mediated A Lejeune responses.[

,antagonists have affinity  but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or  inverse agonist at receptors. Antagonists mediate their effects by binding to the active site or to allosteric sites on receptors, or they may interact at unique binding sites not normally 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

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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
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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.
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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

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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 To i l te exci to ry p o stsyn a p ti p o te n ti l so a ta c as located in the ventral ( EPSPs ) in allrecordings , we used GABA receptor posterior and posterior a n ta g o n i sts medial A Lejeune 19 nuclei.

Synaptic inputs to cells of the lateral geniculate nucleus
W e th u s e l ctri l y sti u l te d e ca l m a th e o p ti tra ct a n d ra d i ti n s w h i e c a o l re co rd i g fro m n g e n i l te re l y ce l s. cu a a l

ra t: G ra n se th a n d Li d stro ¨ m 2 0 0 3 ; Tu rn e r n a n d S a l 1 9 9 8 ; m o u se : C h e n a n d R e g e h r t 2 0 00 ; C hen et al 20 0 2 ; gui ea pi : . n g M cC o rm i a n d V o n K ro si k 1 9 9 2 ; ca t: ck g Li d stro ¨ m a n d W ro ´ e l1 9 9 0 ; a l o u r o w n n b so u n p u b l sh e d o b se rva ti n s i o A Lejeune

To h e l e sta b l sh syn a p ti p ro p e rti s o f p i c e d ri rs a n d co n tra st th e m w i l ye r 6 ve th a m o d u l to r p ro p e rti s w i o u r te ch n i u e s, w e a e th q fi re co rd e d fro m th e l te ra lg e n i l te rst a cu a n u cl u s. e
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FIG. 2. Drivers and modulators in the mouse lateral geniculate nucleus

sh o w i g exci to ry p o stsyn a p ti p o te n ti l n ta c as ( EPSPs ) evoked from stimulation of re ti o g e n i l te a ffe re n ts vi th e o p ti tra ct n cu a a c ( 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 pairedpulse facilitation evoked from corticogeniculate stimulation (Aii). A Lejeune  B, i and ii: increasing

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FIG. 2. Drivers and modulators in the mouse lateral geniculate nucleus

sh o w i g exci to ry p o stsyn a p ti p o te n ti l n ta c as ( EPSPs ) evoked from stimulation of re ti o g e n i l te a ffe re n ts vi th e o p ti tra ct n cu a a c (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 Nmethyl-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

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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
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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

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of the corticothalamic pathway

C o rti th a l m i a xo n s fro m l ye rs 5 co a c a a n d 6 a re o rth o g ra d e l l b e l d b y y a e b i cyti i n to p h o re si i to th e b a rre l o n o s n 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 A Lejeune thalamic reticular

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corticothalamic pathway

C o rti th a l m i a xo n s fro m l ye rs 5 co a c a a n d 6 a re o rth o g ra d e l l b e l d b y y a e b i cyti i n to p h o re si i to th e b a rre l o n o s n 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.

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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

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subcortical stimulation in a cell in the ventral posterior medial nucleus 

The EPSPs evoked 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 the drug application.

A : e x a m p le o f e v o k e d E P S P s. B : p a ire d - p u lse fa cilita tio n a n d g ra d e d re sp o n se o f E P S P s C : e v id e n ce o f a n m G lu R 1 co m p o n e n t. 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 p o te n tia l

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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

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EPSPs evoked from stimulation of layer 6 of barrel cortex in a cell of the posterior medial nucleus 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 : e xa m p l o f e vo ke d E P S Ps e B : p a i d - p u l fa ci i ti n a n d g ra d e d re se l ta o re sp o n se o f E P S Ps C : e vi e n ce o f a n m G l R 1 co m p o n e n t d u

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stimulation of layer 5 of barrel cortex in a cell of the posterior medial nucleus

A : e x a m p le o f e v o k e d E P S P s B : p a ire d - p u lse d e p re ssio n 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 fro m re sp o n se s to in cre a sin g stim u la tio n 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)

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of graded and allor-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 )

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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: pairedpulse effects, showing depression for layer 5 stimulation (Ai) and facilitation for layer 6 stimulation (Aii). B, i and ii: recruitment properties, showing allor-none response for layer 5 stimulation (Bi) and graded responses A Lejeune for layer 6 stimulation

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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

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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

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cortico-thalamocortical 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

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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 ro 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 A Lejeune co rtico co rtica l p a th w a y s a s d riv e r o r

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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.

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Questions ??
Somatosensory Corticothalamic Projections: Distinguishing Drivers from Modulators
  

par

Iva Reichova et S. Murray Sherman Journal of Neurophysiolog y, 2004
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