Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Em roedores, as vibrissas são detectores táteis que desempenham papel importante na exploração espacial do ambiente e na discriminação de texturas. No córtex somatosensorial, os campos receptivos de cada uma das vibrissas estão organizados no hemisfério contralateral em colunas discretas denominadas barris. A lesão unilateral dos barris produz um comportamento assimétrico caracterizado pela redução no uso da vibrissa contralateral à lesão na exploração do ambiente, assimetria esta que diminui progressivamente na medida em que os animais são repetidamente testados. Em ratos, este comportamento, normalmente medido pelo número de vezes que os animais encostam as vibrissas na parede de um campo aberto, tem se mostrado uma ferramenta importante em estudos de plasticidade e recuperação funcional após lesões corticais. Contudo, em camundongos com lesões unilaterais dos barris, o registro dos toques das vibrissas na parede tem levado a resultados contraditórios. Esse trabalho tem por objetivo principal o estabelecimento de um modelo comportamental para avaliação da recuperação funcional após lesões unilaterais dos barris do córtex somatosensorial em camundongos. Para tanto, o sentido dos deslocamentos realizados próximos às quinas do campo aberto foi registrado em camundongos Suíços machos submetidos à criolesão unilateral dos barris foi avaliado em três estudos independentes. No primeiro estudo, demonstramos que no grupo Criolesado houve um predomínio dos deslocamentos em sentido contralateral na primeira vez em que foram testados no campo aberto e este resultado foi independente do fato de na primeira sessão ter sido realizada um ou nove dias após a cirurgia. Além disso, demonstramos que o predomínio de deslocamentos em sentido contralateral foi diminuindo na medida em que os animais eram repetidamente testados no campo aberto. No segundo estudo, demonstramos que os animais do grupo Criolesado que foram previamente submetidos a cinco sessões experimentais no campo aberto não apresentaram, após a cirurgia, diferenças entre os deslocamentos realizados em sentido ipsolateral e contralateral à lesão. Já no terceiro estudo, demonstramos que os animais do grupo Criolesado que não foram previamente testados no campo aberto apresentam um predomínio de deslocamentos em sentido contralateral, mesmo quando o teste foi realizado 48 dias após a lesão unilateral dos barris. Nossos dados sugerem que o sentido dos deslocamentos próximo às quinas do campo aberto pode ser uma ferramenta importante para avaliar a recuperação das lesões unilaterais nos barris do córtex somatosensorial. Além disso, para avaliar a recuperação funcional após a lesão unilateral dos barris do córtex somatossensorial, sem o viés da habituação à situação do teste, os animais devem ser testados apenas uma vez / In rodents, the vibrissae are tactile detectors that have an important role in the spatial exploration of the environment and in texture discrimination. In the somatosensory cortex, the receptive fields of each of the vibrissae are organized into discrete columns, known as barrels, in the contralateral hemisphere. The unilateral lesions of the barrels results in an asymmetric behavior characterized by the reduction in the use of the vibrissae contralateral to the lesion during the exploration of the environment. This asymmetry progressively diminishes as the animal is repeatedly tested in the same environment. In rats, this behavior, usually assessed by the number of times the animals touch the walls of an open field arena with their vibrissae, has been considered a useful tool in studies addressing plasticity and functional recovery after cortical lesions. However, in mice with unilateral lesions of the barrels, the analysis of the number of times that the vibrissae touch the walls have lead to contradictory results. The present work aims to establish a behavioral model for the evaluation of functional recovery after unilateral lesions of the barrel field located in the somatosensory cortex of the mouse. To that end, the direction of movement near the corners of the open field of Swiss male mice subjected to unilateral cryolesion of the barrel was analyzed in three independent studies. In the first study, we demonstrated that the cryolesioned animals displayed a predominance of contralateral movements in the first time that they were tested in the open field and that this result was present whether the animals was first tested one or nine days after the lesion. Furthermore, we demonstrated that the predominance of movements toward the contralateral side of the lesion diminished as the animals were repeatedly tested in the open field. In the second study, we demonstrated that the cryolesioned animals that were, prior to barrel field lesioning, subjected to five sessions in the open field did not display, after lesioning, differences between the number of ipso and contralateral movements. In the third study, we demonstrated that the cryolesioned animals that were not previously tested in the open field displayed a predominance of contralateral movements even if the first test was carried out forty eight days after the unilateral lesion of the barrels. Our data suggest that the analysis of the direction of movement near the corners of the open field can be an important tool in the assessment of functional recovery after unilateral lesions of the barrels located in the somatosensory cortex of mice. Moreover, in order to properly assess functional recovery after unilateral lesion of the barrel field without the confounding factor of habituation, animals must be tested only once

Rett syndrome (RTT), a severe neurodevelopmental disorder, affects females resulting from loss-of-function mutations in the X-linked transcription factor methyl-CpG-binding protein 2 (MECP2). RTT patients show severe verbal, motor, respiratory, and intellectual impairments. We studied two forms of activity-dependent plasticity in Mecp2 mutant mice to better understand the loss of MECP2 function in neuronal circuit and sensory processing. Sensory deprivation was applied by trimming one whisker to 3 mm to study long-term cortical plasticity in Mecp2-/y mice. Intrinsic optical signaling (IOS) imaging showed the neuronal response to wiggling a non-trimmed was consistent from day 0 to 14 but reduced for the trimmed whisker by 49.0 ± 4.3% in wild type (WT) and 22.7 ± 4.6% (p=0.0135) in RTT mice. Primary hindlimb (HL) somatosensory cortical responses to vibratory stimulation were assessed by IOS and intracortical local field potential (LFP). Responses were assessed before, during and, after 1 hour of repeated HL vibratory stimulation (100Hz,1sec, ISI 6 sec) in symptomatic male (4-6 week), female (10-12 month) and pre-symptomatic young female (4 week) RTT model mice. After 1-hour, cortical responses to test vibrations were reduced by approximately 40% in RTT and WT mice as assessed by both methods. Recovery of the IOS responses (1 sec vibration at 100Hz) and LFP (300µm below pia, 7 stimuli, 100mse ISI) were tested at 15 min intervals for 1 hour after ceasing the repeated stimulation. Reduced responses persisted for at least 60 min in WT but recovered to 90-100% of normal within 15-30 min in RTT. Analysis of the LFP responses within the test train indicated that the reduced cortical sensitivity during and after continuous stimulation resulted primarily from an increase in adaptation during the 7-stimulus test train rather than a reduction in the response to a single vibratory stimulus in all groups. Retention of this increased STA is the primary cause of the persistently reduced tactile response in young WT female mice, while in RTT mice the rapid recovery of tactile sensitivity was due to the return of STA to lower, baseline levels. Male RTT mice exhibited a marked increased excitability to the first stimulus in the test train resulting in hypersensitivity to a single vibration by 45 minutes. Old females exhibited the same pattern of adaptation and recovery but retention of adaptation was less pronounced in both WT and RTT compared to younger animals suggesting an age-dependent reduction in neural plasticity may mask deficits specific to RTT. Recording sciatic nerve sensory afferent activity did not reveal any STA, persistent adaptation or sensitization of peripheral afferent endings in any groups. I propose persistent sensory adaptation mediated by increased short-term adaptation may reflect enhanced feedback by inhibitory elements of circuits within the sensory pathway. The rapid recovery of responsiveness in young female RTT mice may therefore reflect a deficit in the capacity for activity dependent plasticity to consolidate and thus could provide a platform to understand the causes of learning and cognitive deficits in RTT patients. / Graduate

Recent evidence indicates that the mature neocortex retains a higher degree of plasticity than traditionally assumed. Up- and down-regulation of synaptic strength, long-term potentiation (LTP) and long-term depression (LTD), is thought to be the primary mechanism mediating experience-dependent plasticity of cortical networks. The present thesis investigate factors that regulate adult cortical plasticity, focusing on the role of neuromodulators, recent sensory experience, and different anatomical divisions of the cortex in influencing synaptic strength. First, I investigated the role of the neuromodulator histamine in gating plasticity in the primary visual cortex (V1) of urethane anesthetized adult rats. Histamine applied locally in V1 produced an enhancement of LTP elicited by theta burst stimulation (TBS) of dorsal lateral geniculate nucleus (dLGN) and allowed a sub-threshold TBS to produce stable LTP. Second, the impact of visual deprivation on LTP in V1 was assessed. Animals that received 2 and 5 hr dark exposure showed greater potentiation of field potentials when stimulated though retinal light flashes or weak TBS of the dLGN, which failed to induce LTP in control animals kept in continuous light. Third, I performed a detailed characterization of LTP induced by different TBS protocols, recording in either the monocular or binocular segment of both V1 hemispheres (i.e., ipsi- and contralateral to the stimulated dLGN). Stronger, NMDA receptor-independent LTP was found in the contralateral V1. Interestingly, weak TBS induced LTD that was NMDA receptor-dependent in the ipsilateral V1. Furthermore, a lower LTP induction threshold was observed in the binocular than the monocular segment of ipsilateral V1. Lastly, I investigated cholinergic modulation of sensory-induced activity in the barrel cortex. Basal forebrain stimulation enhanced multi-unit activity elicited by whisker deflection, an effect that was more pronounced for weaker response driven by a secondary whisker than principal whisker deflection. This thesis demonstrates that neocortical plasticity consists of multiple forms of synaptic modification. Adult cortical plasticity is greatly influenced by preceding activity of the synapse by various neuromodulator systems, and by anatomical subdivisions within primary sensory cortex fields. Together, these mechanisms may facilitate the detection, amplification, and storage of inputs to primary sensory fields of the neocortex. / Thesis (Ph.D, Psychology) -- Queen's University, 2010-04-29 14:02:30.742

Les vibrisses ou moustaches, sont représentées de façon très précise au niveau cortical. Cette représentation forme une carte qui peut varier selon l’expérience ou l’apprentissage. La plasticité corticale est parfois altérée dans des maladies. C’est le cas du syndrome de l’X-fragile où la protéine FMRP n’est plus produite. Notre hypothèse est double : 1- La plasticité opérant dans le cortex somato-sensoriel primaire lors d’un conditionnement associatif est primordiale pour l’apprentissage. 2- FMRP peut perturber cette plasticité et altérer l’acquisition de la mémoire. Mon travail de thèse s’est déroulé sous la direction du Dr Ingrid Bureau, dans l’Institut de neurobiologie de la Méditerranée UMR901, laboratoire de l’INSERM, sur le campus universitaire de Luminy (Aix-Marseille Université).Après un protocole de conditionnement, les souris ayant appris l’association présentent des réorganisations de la carte corticale sélective manifestées par une surreprésentation des vibrisses appariées au dépend des vibrisses voisines.L’étude a ensuite montré que déjà en condition naïve l’excitabilité des neurones glutamatergiques de la couche 4 est plus importante que chez les souris mutantes, dans lequel la synthèse de FMRP n’est inactivée que dans la couche 4 du cortex somato-sensoriel. Ceci est couplé à une baisse de la probabilité de libération de neurotransmetteur et une baisse de connectivité. Les cartes corticales sauvages et mutantes en condition naïve sont donc en apparence similaires. Après altération de l’expérience sensorielle, nous avons observé une forte augmentation de la force des projections ascendantes de la couche 4 vers la couche 2/3 chez les individus mutants / Whiskers representation is well defined at cortical level. This representation designs a map which can be modified with sensory experiece or learning. Cortical plasticity is sometime affected by diseases such as the fragile-X syndrome where protein FMRP is lacking. Two hypothesis : 1- Plasticity in primary somatosensory cortex play a major role in learning. 2- FMRP can disturb that plasticity and so memory acquisition.After playing an associtiative conditionning protocol, some mice learn the association and cortical map changes in a selective way with a gain of representation for the paired whiskers vs whiskers in neighbourghood.We’ve after shown that in naive conditions, layer 4 glutamatergic neurons present an increase of excitability in mutant mice, in which FMRP synthesis is inactivated only in layer 4 of somatosensory cortex. This phenotype comes with a decrease in neurotransmetor release probability and a decrease in connectivity. This way, WT and mutant cortical maps appear similar in naive conditions. But after sensory alteration we’ve seen a huge increase in strenght of ascending projections from layer 4 to layer 2/3 in mutants. We don’t know yet how to explain thoose deregulations.

Prenatal alcohol exposure (PAE) alters limb development that may lead to structural and functional abnormalities of the limb reported in children diagnosed with Fetal Alcohol Spectrum Disorder. To determine whether PAE alters the central representation of the forelimb we used the rodent barrel cortex as our model system where it was possible to visualize and quantitatively measure the size of the forepaw representation in the forepaw barrel subfield (FBS) in first somatosensory cortex. In the present study, we examined the effects of PAE on pattern and size of the forepaw and forepaw representation in FBS in neonatal rats at gestational day 32 that corresponds to postnatal day 9. Pregnant Sprague-Dawley rats were chronically intubated with binge doses of ethanol (6 g/kg) from gestational day 1 through gestational day 20. The offspring of the ethanol treated dams comprised the ethanol (EtOH) group. The effect of PAE on the EtOH group was compared with a nutritional-controlled pairfed (PF) group and a normal chowfed (CF) group. The ventral (glabrous) surface area of the forepaw digits, length of digit 2 through digit 5, and the corresponding glabrous forepaw digit representations in the FBS were measured and compared between treatment groups. In rats exposed to in utero alcohol, the sizes of the overall glabrous forepaw and forepaw digits were significantly reduced in EtOH pups compared to CF and PF pups; overall glabrous forepaw area was 11% smaller than CF controls. Glabrous digit lengths were also smaller in EtOH rats compared to CF controls and significantly smaller in digit 2 through digit 4. The glabrous digit representation in FBS was 18% smaller in the EtOH group when compared to the CF treatment. However, PAE did not produce malformations in the forepaw or alter the pattern of the forepaw representation in FBS; instead, PAE significantly reduced both body and brain weights compared to controls. Unexpectedly, little or no correlation was observed between the size of the glabrous forepaw compared to the size of the glabrous forepaw representation in the FBS for any of the treatment groups. The present findings of PAE-related alterations in sensory periphery and the central cortical representation may underlie deficits in sensorimotor integration reported among children with Fetal Alcohol Spectrum Disorder.

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L'objectif de ce projet est l’étude de la plasticité des circuits corticaux dans le contexte de l'apprentissage des souris « sauvages » et modèles du syndrome de l’X fragile. Des études sur l'efficacité de la combinaison d'enregistrement des potentiels de champ locaux extracellulaires avec la stimulation laser UV (LSPS) pour cartographier les réseaux ont été réalisées. Nous avons trouvé des enregistrements de champs extracellulaires qui pourraient être utilisés pour détecter les réponses synaptiques évoquées par LSPS. Nos résultats indiquent une méthode alternative pour obtenir des cartes complètes de réseaux intracorticaux excitateurs. Ensuite, nous avons développé un paradigme d'apprentissage associatif sensoriel et étudié ses effets sur les réseaux intracorticaux excitateurs du cortex baril. Ex vivo un affaiblissement des projections excitatrices entre les couches 4 et 2/3 qui dans les colonnes de vibrisses C a été observée. Enfin, nous avons utilisé ces mêmes approches dans une souris modèle du syndrome de l'X fragile (FXS). Pour étudier les liens entre les déficits sensoriels, l'apprentissage associatif et les altérations fonctionnelles des réseaux sensoriels, nous avons utilisé un modèle de souris mutantes dans lequel la pathologie FXS était ciblée sur la couche 4 du cortex somatosensoriel. Il a été constaté que les souris WT présentaient une dépression similaire, alors qu'elle était absente FXS. En conclusion, les études sur les mutants sensoriels de type sauvage ont mis en lumière les conséquences de l'apprentissage sur les réseaux corticaux sensoriels et les liens entre la plasticité des réseaux corticaux sensoriels et les capacités cognitives. / The aim of this project is to study the plasticity of the cortical circuits in the context of the learning of wild type mice and models of Fragile X Syndrome. First, investigations into the efficacy of recording combination of extracellular local field potentials with UV laser stimulation (LSPS) to map networks were performed. We found extracellular field records could be used to detect the synaptic responses evoked by LSPS. Our results indicate an alternative method for obtaining complete maps of excitatory intracortical networks. Next, we developed a sensory associative learning paradigm and studied its effects on excitatory intracortical networks the barrel cortex. Ex vivo a weakening of the excitatory projections between layers 4 and 2/3 which in the columns of vibrissae C was observed and declined function of the speed of the behavioural response. Finally, we used these same approaches in a Fragile X Syndrome (FXS) model mouse. To study the links between sensory deficits, associative learning, and functional alterations of sensory networks, we used a model of mutant mice in which the FXS pathology was targeted to the layer 4 of the somatosensory cortex. Our hypotheses were that behavioural conditioning would change the cortical sensory circuits of the FXS sensory mutant and that the abnormal plasticity of these circuits would in turn affect the performance. It was found the WT mice exhibited a similar depression, whereas it was absent FXS. In conclusion, wild type mouse and FXS sensory mutant studies shed light on the consequences of learning on sensory cortical networks and on the links between plasticity of sensory cortical networks and cognitive abilities.

Lorsque les rongeurs explorent leur environnement, ils contactent activement les objets environnants avec leurs vibrisses qui sont ainsi défléchies selon des séquences spatiotemporelles complexes. Le système vibrissal est néanmoins capable d'extraire des informations pertinentes de ces stimulations pour générer un comportement tactile-dépendant. Une question se pose alors: Comment l’information multivibrissale globale est-elle encodée? La représentation corticale des vibrisses au sein du cortex somatosensoriel primaire (S1) du rongeur est dotée de structures anatomiquement remarquables, nommées "tonneaux", au niveau de la couche IV, qui sont organisées de la même manière que les vibrisses sur le museau de l’animal. A chaque "tonneau" correspond une colonne corticale, unité de traitement de l’information, qui reçoit en priorité les informations provenant la vibrisse principale (VP) correspondante. Des enregistrements extracellulaires réalisés dans notre équipe chez le rat ont révélé que les réponses des neurones du cortex S1 et du thalamus sont non seulement sensibles à la direction de déflection locale de leur VP, mais aussi à la direction d'un mouvement global de l’ensemble de leurs vibrisses. Afin de mieux comprendre la manière dont le réseau cortical traite ces scènes tactiles globales, nous avons construit un poste expérimental permettant d’enregistrer en temps réel l’activité du cortex S1 chez la souris par imagerie sensible au potentiel, tout en appliquant des stimuli tactiles complexes à l'aide d'une matrice de 24-stimulateurs vibrissaux. Nous avons de plus développé une méthode permettant d’aligner les données fonctionnelles ainsi obtenues par rapport la carte cytoarchitecturale du réseau cortical sous-jacent. Nous avons ainsi étudié premièrement la distribution spatiale de la sélectivité à la direction de déflection locale d’une vibrisse au niveau d’une colonne corticale. Les réponses aux différentes directions étaient localisées de manière légèrement distincte, autour du centre de la colonne, mais selon une organisation différente de celle précédemment décrite chez le rat. Nous avons montré par la suite que la sélectivité à la direction globale est spatialement organisée dans le cortex "en tonneaux" à l’échelle supra-colonnaire. Les colonnes correspondant aux vibrisses rostrales étant plus sélectives à la direction globale que les colonnes associées aux vibrisses caudales. En outre, les colonnes correspondant aux vibrisses dorsales répondent préférentiellement aux directions globales ventrales, tandis que les colonnes associées aux vibrisses ventrales répondent préférentiellement aux directions globales caudales. Enfin, les réponses induites par des directions globales caudo-ventrales étaient en moyenne les plus fortes pour toutes les colonnes. Nous avons montré que la répartition spatiale de la sélectivité à la direction globale peut être expliquée ni par la saillance prédominante de la position de départ de la séquence de stimulation multivibrissale (effet de bord), ni par la sommation linéaire des réponses aux déflections de quelques vibrisses. Les réponses aux stimulations globales de l'ensemble des vibrisses sont en effet fortement sous-linéaires, indépendamment de la direction de la stimulation. Brièvement, nous montrons ici que sortir de la vision classique du système vibrissal permet une meilleure compréhension de la façon dont les différentes caractéristiques des stimuli complexes sont traitées et de la manière dont les propriétés émergentes du cortex, comme la sélectivité à la direction globale, sont construites. / While rodents explore their environment they actively contact surrounding objects with their array of whiskers, resulting in a complex pattern of multiwhisker deflections. Despite this complexity, the whisker system is able to extract relevant information from the spatiotemporal sequence of deflections to generate touch-dependent behavior. The question that arises is: How is global multiwhisker information encoded? Whiskers are mapped onto layer 4 of the primary somatosensory cortex (S1) as discrete units named “barrels”. Each barrel-related vertical column processes information coming primarily from its corresponding principal whisker (PW). Previous experiments in our lab done with extracellular recordings have revealed that neurons in the rat S1 and thalamus not only show a preferred direction for the local deflection of the PW but also for the direction of a global motion across the whisker pad. To further understand how the cortical network processes global tactile scenes, we built a set-up that enables to perform voltage sensitive dye imaging of the mouse barrel cortex while applying precise tactile stimuli using a 24-multi-whisker stimulator. We further developed a technical method to map the recorded functional data onto the cortical structure. We first studied whether local direction selectivity is spatially distributed within the barrel-related column. Responses to different directions were slightly segregated on space close to the barrel center, but the distribution differed from the one previously described in rat S1, namely a pinwheel-like structure. We then showed that global direction selectivity is spatially organized in the barrel cortex. Columns related to rostral whiskers were more selective to the global direction than columns related to caudal whiskers. Moreover, the columns related to dorsal whiskers preferred ventral global directions, while the columns related to ventral whiskers preferred caudal global directions. Overall the responses to the caudo-ventral global directions were the strongest in average for all the columns. We showed that the spatial distribution of the global direction selectivity can be explained neither by the high salience of the starting position of the deflections on the whiskerpad (a border effect), nor by the linear summation of the responses to deflections of several whiskers. Responses to the global motion of the whisker array are indeed highly sublinear independently of the direction of stimulation. In conclusion, we show here that stepping aside from the classical view of the whisker-to-barrel cortex system allows a better understanding of how different features of complex stimuli are processed and how the emergent properties of the cortex, like the global direction selectivity, are built-up.

Neuroligine (NL) sind vorwiegend postsynaptisch lokalisierte transmembrane Adhäsionsmoleküle, die in Wechselwirkung mit dem präsynaptisch lokalisierten Protein Neurexin eine wichtige Rolle in der Reifung und Funktion von Synapsen spielen. Es existieren verschiedene NL-Isoproteine (NL-1 – NL-4), die sich in ihrer Assoziation zu exzitatorischen und inhibitorischen Synapsen unterscheiden. Die funktionelle und klinische Relevanz der Neuroligine belegen beispielhaft Mutationen des Isotyps NL 4, welche mit neuropsychiatrischen Erkrankungen wie Autismus-Spektrum-Störungen assoziiert vorkommen. Anhand eines durch Ausschalten des human-orthologen NL-4-Gens generierten Mausmodells (NL 4 Knockout, NL 4 KO) konnte in vorhergehenden Studien die Bedeutung einer immunhistochemisch beobachteten Lokalisation von NL 4 an glycinergen Synapsen der Retina für die inhibitorische synaptische Übertragung nachgewiesen werden. Im Unterschied dazu konnte kein Zusammenhang zwischen einer in Schicht IV des Barrel-Kortex nachweisbaren Lokalisation von NL-4 mit inhibitorischen Synapsen hergestellt werden. Deshalb, und aufgrund der in Schicht IV dominierenden exzitatorischen Verschaltung von thalamischen Projektionen und den kolumnenassoziierten Rückverschaltungen aus dem Neokortex, lässt sich eine Interaktion von NL-4 mit exzitatorischen Synapsen in diesem Areal vermuten. Im Rahmen der vorliegenden Arbeit wurde anhand der NL-4-KO-Modellmaus der Frage nachgegangen, inwiefern NL-4 die exzitatorische synaptische Übertragung im Barrel-Kortex beeinflusst. Dafür wurden mit Hilfe der Patch-Clamp-Technik abgeleitete AMPA-Rezeptor-vermittelte exzitatorische postsynaptische Ströme (EPSC) von bedornten Sternzellen, Sternpyramiden- und Pyramidenzellen der Schicht IV ausgewertet und zwischen NL-4-Wildtyp- (NL 4-WT) und NL 4 KO-Neuronen verglichen. Dabei zeigten NL 4-KO-Neurone signifikant veränderte Parameter der EPSC-Kinetik. Die Abfallszeit war in NL 4 KO-Neuronen signifikant länger, das maximale Gefälle und die maximale Steigung signifikant flacher gegenüber NL-4-WT-Kontrollen. Diese Veränderungen sprechen für eine funktionelle Relevanz von NL-4 für die AMPA-Rezeptor-vermittelte synaptische Übertragung auf exzitatorische Neurone in Schicht IV des Barrel-Kortex. Das Muster der in NL-4-KO-Neuronen veränderten EPSC-Kinetik weist dabei auf eine Modulation der biophysikalischen AMPA-Rezeptoreigenschaften hin und könnte mit Veränderungen der synaptisch exprimierten AMPA-Rezeptor-TARP-Subtypen in Zusammenhang stehen, die über Proteine der postsynaptischen Dichte (wie PSD-95 und S SCAM) mit Neuroliginen interagieren.