Experience Dependence of Alpha Rhythms and Neural Dynamics in the Mouse Visual Cortex.

The role of experience in the development and maintenance of emergent network properties such as cortical oscillations and states is poorly understood. To define how early-life experience affects cortical dynamics in the visual cortex of adult, head-fixed mice, we examined the effects of two forms of blindness initiated before eye opening and continuing through recording: (1) bilateral loss of retinal input (enucleation) and (2) degradation of visual input (eyelid suture). Neither form of deprivation fundamentally altered the state-dependent regulation of firing rates or local field potentials. However, each deprivation caused unique changes in network behavior. Laminar analysis revealed two different generative mechanisms for low-frequency synchronization: one prevalent during movement and the other during quiet wakefulness. The former was absent in enucleated mice, suggesting a mouse homolog of human alpha oscillations. In addition, neurons in enucleated animals were less correlated and fired more regularly, but no change in mean firing rate. Eyelid suture decreased firing rates during quiet wakefulness, but not during movement, with no effect on neural correlations or regularity. Sutured animals showed a broadband increase in depth EEG power and an increased occurrence, but reduced central frequency, of narrowband gamma oscillations. The complementary-rather than additive-effects of lid suture and enucleation suggest that the development of emergent network properties does not require vision but is plastic to modified input. Our results suggest a complex interaction of internal set points and experience determines mature cortical activity, with low-frequency synchronization being particularly susceptible to early deprivation.

Homeostatic regulation through strengthening of neuronal network-correlated synaptic inputs.

Homeostatic regulation is essential for stable neuronal function. Several synaptic mechanisms of homeostatic plasticity have been described, but the functional properties of synapses involved in homeostasis are unknown. We used longitudinal two-photon functional imaging of dendritic spine calcium signals in visual and retrosplenial cortices of awake adult mice to quantify the sensory deprivation-induced changes in the responses of functionally identified spines. We found that spines whose activity selectively correlated with intrinsic network activity underwent tumor necrosis factor alpha (TNF-α)-dependent homeostatic increases in their response amplitudes, but spines identified as responsive to sensory stimulation did not. We observed an increase in the global sensory-evoked responses following sensory deprivation, despite the fact that the identified sensory inputs did not strengthen. Instead, global sensory-evoked responses correlated with the strength of network-correlated inputs. Our results suggest that homeostatic regulation of global responses is mediated through changes to intrinsic network-correlated inputs rather than changes to identified sensory inputs thought to drive sensory processing.

Ocular dominance plasticity: Molecular mechanisms revisited.

Ocular dominance plasticity (ODP) is a type of cortical plasticity operating in visual cortex of mammals that are endowed with binocular vision based on the competition-driven disparity. Earlier, a molecular mechanism was proposed that catecholamines play an important role in the maintenance of ODP in kittens. Having survived the initial test, the hypothesis was further advanced to identify noradrenaline (NA) as a key factor that regulates ODP in the immature cortex. Later, the ODP-promoting effect of NA is extended to the adult with age-related limitations. Following the enhanced NA availability, the chain events downstream lead to the ß-adrenoreceptor-induced cAMP accumulation, which in turn activates the protein kinase A. Eventually, the protein kinase translocates to the cell nucleus to activate cAMP responsive element binding protein (CREB). CREB is a cellular transcription factor that controls the transcription of various genes, underpinning neuronal plasticity and long-term memory. In the advent of molecular genetics in that various types of new tools have become available with relative ease, ODP research has lightly adopted in the rodent model the original concepts and methodologies. Here, after briefly tracing the strategic maturation of our quest, the review moves to the later development of the field, with the emphasis placed around the following issues: (a) Are we testing ODP per se? (b) What does monocular deprivation deprive of the immature cortex? (c) The critical importance of binocular competition, (d) What is the adult plasticity? (e) Excitation-Inhibition balance in local circuits, and (f) Species differences in the animal models.

The effect of optic nerve section on form deprivation myopia in the guinea pig.

Myopia is induced when a growing eye wears a diffuser that deprives it of detailed spatial vision (form deprivation, FD). In chickens with optic nerve section (ONS), FD myopia still occurs, suggesting that the signals underlying myopia reside within the eye. As avian eyes differ from mammals, we asked whether local mechanisms also underlie FD myopia in a mammalian model. Young guinea pigs underwent either sham surgery followed by FD (SHAM + FD, n = 7); or ONS followed by FD (ONS + FD, n = 7); or ONS without FD (ONS, n = 9). FD was initiated 3 days after surgery with a diffuser that was worn on the surgically treated eye for 14 days. Animals with ONS + FD developed -8.9 D of relative myopia and elongated by 135 µm more than in their untreated eyes after 2 weeks of FD. These changes were significantly greater than those in SHAM + FD animals (-5.5 D and 40 µm of elongation after 14 days of FD), and reflected exaggerated elongation of the posterior vitreous chamber. The myopia reversed when FD was discontinued, despite ONS, but eyes did not recover back to normal (30 days after surgery, ONS + FD eyes still retained -3 D of relative myopia when SHAM+FD animals had returned to normal). No long-term residual myopia was present after ONS alone, ruling out a surgical artifact. Although the gross mechanism signaling myopic ocular growth and its recovery in the young mammalian eye does not require an intact optic nerve, its fine-tuning is disrupted by ONS.

Dark exposure affects plasticity-related molecules and interneurons throughout the visual system during adulthood.

Several experimental manipulations, including visual deprivation, are able to induce critical period-like plasticity in the visual cortex of adult animals. In this regard, many studies have analyzed the effects of dark exposure in adult animals, but still little is known about the role of interneurons and plasticity-related molecules on such mechanisms. In this study, we analyzed the effects of 10 days of dark exposure on the connectivity and structure of interneurons, both in the primary visual cortex and in the rest of cerebral regions implicated in the transmission of visual stimulus. We found that this environmental manipulation induces changes in the expression of synaptic molecules throughout the visual pathway and in the structure of interneurons in the primary visual cortex. Moreover, we found altered expression in the polysialylated form of the neural cell adhesion molecule and in perineuronal nets surrounding parvalbumin expressing interneurons, suggesting that these plasticity-related molecules may be involved in the changes produced by dark exposure. Together, our findings indicate that dark exposure produces an important alteration of inhibitory circuits and molecules related to their plasticity, not only in the visual cortex but throughout the visual pathway.

Neuregulin and ErbB expression is regulated by development and sensory experience in mouse visual cortex.

Neuregulins (NRGs) are protein ligands that impact neural development and circuit function. NRGs signal through the ErbB receptor tyrosine kinase family. NRG1/ErbB4 signaling in parvalbumin-expressing (PV) inhibitory interneurons is critical for visual cortical plasticity. There are multiple types of NRGs and ErbBs that can potentially contribute to visual cortical plasticity at different developmental stages. Thus, it is important to understand the normal developmental expression profiles of NRGs and ErbBs in specific neuron types in the visual cortex, and to study whether and how their expression changes in PV inhibitory neurons and excitatory neurons track with sensory perturbation. Cell type-specific translating ribosome affinity purification and qPCR was used to compare mRNA expression of nrg1,2,3,4 and erbB1,2,3,4 in PV and excitatory neurons in mouse visual cortex. We show that the expression of nrg1 and nrg3 decreases in PV neurons at the critical period peak, postnatal day 28 (P28) after monocular deprivation and dark rearing, and in the adult cortex (at P104) after 2-week long dark exposure. In contrast, nrg1 expression by excitatory neurons is unchanged at P28 and P104 following sensory deprivation, whereas nrg3 expression by excitatory neurons shows changes depending on the age and the mode of sensory deprivation. ErbB4 expression in PV neurons remains consistently high and does not appear to change in response to sensory deprivation. These data provide new important details of cell type-specific NRG/ErbB expression in the visual cortex and support that NRG1/ErbB4 signaling is implicated in both critical period and adult visual cortical plasticity.

Therapeutic effect of vasoactive intestinal peptide on form-deprived amblyopic kittens.

BACKGROUND: Exploring the role of vasoactive intestinal peptide (VIP) in the lateral geniculate body (LGBd) in visual development and studying the therapeutic effect of VIP on amblyopic kittens. METHODS: Three-week-old domestic cats were divided into a control group (n = 10) and a monocular deprivation group (n = 20), with an eye mask covering the right eye of those in the deprived group. After pattern visual evoked potential (PVEP) recording confirmed the formation of monocular amblyopia, the left LGBd was isolated from 5 kittens in each group. The remaining control kittens continued to be raised, and the remaining deprivation group was divided into a VIP intervention group (n = 5), Sefsol (caprylic acid monoglyceride, VIP solution) intervention group (n = 5) and amblyopia non-intervention group (n = 5) after removal of the eye mask. Three weeks later, PVEPs, VIP immunohistochemistry and VIP mRNA expression in the left LGBd were compared across groups. RESULTS: At 6 weeks of age, there were significant differences in P100 wave latency and amplitude and VIP immunohistochemistry and in situ hybridization between the control group and the deprivation group (P < 0.05). After 3 weeks of the corresponding interventions, the latency and amplitude in the VIP intervention group were better than that in the Sefsol intervention group and amblyopia non-intervention group (P < 0.05). Furthermore, VIP treatment increased the number of immunohistochemical VIP-positive cells (P < 0.05) and the average optical density of positive cells (P > 0.05), as well as the number (P < 0.05) and average optical density of VIP mRNA-positive cells (P < 0.05). CONCLUSIONS: VIP plays an important role in visual development. Nasal administration of VIP can improve the function of neurons in the LGBd of kittens and has a certain therapeutic effect on amblyopia.

Short and long-term visual deprivation leads to adapted use of audiovisual information for face-voice recognition.

Person identification is essential for everyday social interactions. We quickly identify people from cues such as a person's face or the sound of their voice. A change in sensory input, such as losing one's vision, can alter how one uses sensory information. We asked how people with only one eye, who have had reduced visual input during postnatal maturation of the visual system, use faces and voices for person identity recognition. We used an old/new paradigm to investigate unimodal (visual or auditory) and bimodal (audiovisual) identity recognition of people (face, voice and face-voice) and a control category, objects (car, horn and car-horn). Participants learned the identity of 10 pairs of faces and voices (Experiment 1) and 10 cars and horns (Experiment 2) and were asked to identify the learned face/voice or car/horn among 20 distractors. People with one eye were more sensitive to voice identification compared to controls viewing binocularly or with an eye-patch. However, both people with one eye and eye-patched viewing controls use combined audiovisual information for person identification more equally than binocular viewing controls, who favour vision. People with one eye were no different from controls at object identification. The observed visual dominance for binocular controls is larger for person compared to object identification, indicating that faces (vision) play a larger role in person identification and that person identity processing is unique from that for objects. People with long-term visual deprivation from the loss of one eye may have adaptive strategies, such as placing less reliance on vision to achieve intact performance, particularly for face processing.

Role of Cyclic Adenosine Monophosphate in Myopic Scleral Remodeling in Guinea Pigs: A Microarray Analysis.

Purpose: Myopia induction accompanies increased scleral cyclic adenosine phosphate (cAMP) levels and collagen degradation in mammalian models. We compared the scleral gene expression changes following monocular form deprivation (FD) with those induced by adenylate cyclase activation with forskolin (FSK) in guinea pigs. Methods: Guinea pigs were assigned to FD, FSK-treated, and age-matched (AM) control groups. FSK was injected monocularly into the inferior palpebral subconjunctiva daily for 4 days. After scleral RNA extraction, a gene microarray scanner and software were used to evaluate the gene expression patterns, followed by pathway analysis using Gene Ontology tools. Quantitative PCR (qPCR) was used to analyze the expression of 10 candidate genes in separate sets of form-deprived, vehicle-injected, and AM animals. Results: FSK injections differentially regulated 13 collagen subtypes compared to AM and FD groups. FSK also downregulated Acta2 and Tgf-ß2 compared to the AM eyes. Collagen subtypes and Acta2 underwent larger downregulation in the FSK group than during FD. FSK differentially regulated Rarb, Rxrg, Fzd5, Ctnnd2, Dkk2, and Dkk3, which have been linked to ocular growth. Only a few genes were differentially expressed between the FD and AM groups. There was 80% agreement in the direction of gene regulation between microarray and qPCR results. No significant differences were identified between vehicle-injected and AM eyes. Conclusions: Collagen, a major scleral extracellular matrix component, is degraded during myopia. Given that FSK and FD both promote myopia through increased collagen degradation, targeting cAMP signaling pathway genes could suppress myopia development.

Surgical timing for bilateral simultaneous cochlear implants: When is best?

INTRODUCTION: Hearing loss is considered the most common congenital disease and the prevalence of neonatal deafness can be estimated between 1 and 2 cases per 1000 live births. Infant deafness must be diagnosed as early as possible and an effective therapeutic intervention needs to be carried out in order to avoid the serious consequences of hearing deprivation during the evolutionary period: alterations in the development of central auditory pathways and lack of language acquisition. The cochlear implant (CI) has proved to be the best instrument to solve the problem of auditory deprivation. In particular, the bilateral CI gives the patient access to binaural hearing which results in benefits in terms of sound localisation and discrimination. The optimal age of application of the CI is a widely discussed topic in the scientific community and the current guidelines indicate a period between 12 and 24 months of age, even though the supporters of the application before 12 months of age are nowadays increasing. MATERIALS AND METHODS: The study is observational, retrospective, monocentric. 49 paediatric patients (<18 years) with simultaneous bilateral CIs were included. The audiometric threshold and speech tests were carried out during the follow-up 3, 6 and 12 months after the CIs activation and when the patient reached 2 years of age. RESULTS: The statistical analysis showed that undergoing bilateral implantation surgery before 2 years of age allows a satisfactory audiometric performance, while there are no particular benefits in performing the surgery before 1 year of age. As far as the speech outcome is concerned, the statistical analysis didn't show significant correlation between the earlier age of implantation and better speech performance if the operation is carried out before 2.5 years of age. CONCLUSIONS: The results of the study indicate that the optimal age to perform the simultaneous bilateral CIs surgery is between 12 and 24 months, without demonstrating any particular benefit in carrying out the procedure before 1 year of age. This may be clinically relevant in terms of avoiding the risks of diagnostic mistakes and reducing the related surgical risk in children under 1 year of age.

Transient and localized optogenetic activation of somatostatin-interneurons in mouse visual cortex abolishes long-term cortical plasticity due to vision loss.

Unilateral vision loss through monocular enucleation (ME) results in partial reallocation of visual cortical territory to another sense in adult mice. The functional recovery of the visual cortex occurs through a combination of spared-eye potentiation and cross-modal reactivation driven by whisker-related, somatosensory inputs. Brain region-specific intracortical inhibition was recently recognized as a crucial regulator of the cross-modal component, yet the contribution of specific inhibitory neuron subpopulations remains poorly understood. Somatostatin (SST)-interneurons are ideally located within the cortical circuit to modulate sensory integration. Here we demonstrate that optogenetic stimulation of visual cortex SST-interneurons prior to eye removal decreases ME-induced cross-modal recovery at the stimulation site. Our results suggest that SST-interneurons act as local hubs, which are able to control the influx and extent of cortical cross-modal inputs into the deprived cortex. These insights critically expand our understanding of SST-interneuron-specific regulation of cortical plasticity induced by sensory loss.

Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss.

Synaptic scaling is a key homeostatic plasticity mechanism and is thought to be involved in the regulation of cortical activity levels. Here we investigated the spatial scale of homeostatic changes in spine size following sensory deprivation in a subset of inhibitory (layer 2/3 GAD65-positive) and excitatory (layer 5 Thy1-positive) neurons in mouse visual cortex. Using repeated in vivo two-photon imaging, we find that increases in spine size are tumor necrosis factor alpha (TNF-α) dependent and thus are likely associated with synaptic scaling. Rather than occurring at all spines, the observed increases in spine size are spatially localized to a subset of dendritic branches and are correlated with the degree of recent local spine loss within that branch. Using simulations, we show that such a compartmentalized form of synaptic scaling has computational benefits over cell-wide scaling for information processing within the cell.

Rehabilitation modality and onset differentially influence whisker sensory hypersensitivity after diffuse traumatic brain injury in the rat.

BACKGROUND: As rehabilitation strategies advance as therapeutic interventions, the modality and onset of rehabilitation after traumatic brain injury (TBI) are critical to optimize treatment. Our laboratory has detected and characterized a late-onset, long-lasting sensory hypersensitivity to whisker stimulation in diffuse brain-injured rats; a deficit that is comparable to visual or auditory sensory hypersensitivity in humans with an acquired brain injury. OBJECTIVE: We hypothesize that the modality and onset of rehabilitation therapies will differentially influence sensory hypersensitivity in response to the Whisker Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response in diffuse brain-injured rats and shams. METHODS: After midline fluid percussion brain injury (FPI) or sham surgery, rats were assigned to one of four rehabilitative interventions: (1) whisker sensory deprivation during week one or (2) week two or (3) whisker stimulation during week one or (4) week two. At 28 days following FPI and sham procedures, sensory hypersensitivity was assessed using the WNT. Plasma CORT was evaluated immediately following the WNT (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non-aggravated levels). RESULTS: Deprivation therapy during week two elicited significantly greater sensory hypersensitivity to the WNT compared to week one (p < 0.05), and aggravated CORT levels in FPI rats were significantly lower than sham levels. Stimulation therapy during week one resulted in low levels of sensory hypersensitivity to the WNT, similar to deprivation therapy and naïve controls, however, non-aggravated CORT levels in FPI rats were significantly higher than sham. CONCLUSION: These data indicate that modality and onset of sensory rehabilitation can differentially influence FPI and sham rats, having a lasting impact on behavioral and stress responses to the WNT, emphasizing the necessity for continued evaluation of modality and onset of rehabilitation after TBI.

Trunk sway in idiopathic normal pressure hydrocephalus-Quantitative assessment in clinical practice.

BACKGROUND: In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body-worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)). METHODS: Trunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group. RESULTS: Preoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p<0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p<0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p<0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture. CONCLUSIONS: INPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up.

Interictal abnormal fMRI activation of visual areas during a motor task cued by visual stimuli in migraine / Ativação interictal anormal de áreas visuais por ressonância magnética funcional durante uma tarefa visuo-motora em indivíduos com enxaqueca

ABSTRACT Objective To assess changes in blood-oxygen-level-dependent activity after light deprivation compared to regular light exposure in subjects with migraine in the interictal state and in controls. Methods Ten subjects with migraine and ten controls participated in two sessions of functional magnetic resonance imaging. In each session, they performed a finger-tapping task with the right hand, cued by visual stimuli. They were scanned before and after 30 minutes of light deprivation or light exposure. In subjects with migraine, functional magnetic resonance imaging was performed interictally. Analysis of variance was made with the factors time (before or after), session (light deprivation or exposure), and group (migraine or control). Results There were significant “group” effects in a cluster in the bilateral cuneus encompassing the superior border of the calcarine sulcus and extrastriate cortex. There were no significant effects of “time”, “session”, or interactions between these factors. Conclusion The main result of this study is consistent with aberrant interictal processing of visual information in migraine. Light deprivation did not modulate functional magnetic resonance imaging activity in subjects with or without migraine.

RESUMO Objetivo Avaliar mudanças na atividade cerebral por meio de ressonância magnética funcional após privação luminosa comparada à exposição à luz, em indivíduos com enxaqueca no estado interictal e em controles. Métodos Dez indivíduos com enxaqueca e dez controles participaram de duas sessões de ressonância magnética funcional. Em cada sessão, realizaram uma tarefa motora com a mão direita guiada por estímulos visuais. Foram colhidas imagens antes e após 30 minutos de privação luminosa ou exposição à luz. Em indivíduos com enxaqueca, a ressonância funcional foi realizada no período interictal. Foi feita a análise de variância com fatores tempo (antes ou depois), sessão (privação ou exposição à luz) e grupo (enxaqueca ou controle). Resultados Houve efeitos significativos de “grupo” em uma área no cúneo bilateral, incluindo a borda superior do sulco calcarino e o córtex extraestriado. Não houve efeitos significativos de “tempo”, “sessão” ou interações entre estes fatores. Conclusão O principal resultado deste estudo sugere um processamento interictal anormal das informações visuais em indivíduos com enxaqueca. A privação luminosa não modulou a atividade na ressonância magnética funcional em indivíduos com ou sem enxaqueca.

c-FOS expression in the visual system of tree shrews after monocular inactivation.

Tree shrews possess an unusual segregation of ocular inputs to sublayers rather than columns in the primary visual cortex (V1). In this study, the lateral geniculate nucleus (LGN), superior colliculus (SC), pulvinar, and V1 were examined for changes in c-FOS, an immediate-early gene, expression after 1 or 24 hours of monocular inactivation with tetrodotoxin (TTX) in tree shrews. Monocular inactivation greatly reduced gene expression in LGN layers related to the blocked eye, whereas normally high to moderate levels were maintained in the layers that receive inputs from the intact eye. The SC and caudal pulvinar contralateral to the blocked eye had greatly (SC) or moderately (pulvinar) reduced gene expressions reflective of dependence on the contralateral eye. c-FOS expression in V1 was greatly reduced contralateral to the blocked eye, with most of the expression that remained in upper layer 4a and lower 4b and lower layer 6 regions. In contrast, much of V1 contralateral to the active eye showed normal levels of c-FOS expression, including the inner parts of sublayers 4a and 4b and layers 2, 3, and 6. In some cases, upper layer 4a and lower 4b showed a reduction of gene expression. Layers 5 and sublayer 3c had normally low levels of gene expression. The results reveal the functional dominance of the contralateral eye in activating the SC, pulvinar, and V1, and the results from V1 suggest that the sublaminar organization of layer 4 is more complex than previously realized. J. Comp. Neurol. 525:151-165, 2017. © 2016 Wiley Periodicals, Inc.

ß-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity.

The over-production of ß-amyloid (Aß) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer's disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function. Here, we report that during HSP by neuronal activity deprivation, application of Aß results in an aberrant over-response of the up-regulation of AMPA receptor (AMPAR)-mediated synaptic currents and cell-surface AMPAR expression. In the visual cortex, in vivo HSP induced by visual deprivation shows a similar over-response following an Aß local injection. Aß increases the expression of GluA2-lacking, calcium permeable AMPARs (CP-AMPARs), which are required for the initiation, but not maintenance of HSP. Both GluA2-lacking and GluA2-containing AMPARs contribute to the Aß-mediated over-scaling of HSP. We also find that Aß induces the dissociation of HDAC1 from the miR124 transcription factor EVI1, leading to an up-regulation of miR124 expression and increased amount of CP-AMPARs. Thus, via aberrant stimulation of miR124 expression and biogenesis of CP-AMPARs, Aß is able to induce an over response in HSP. This Aß-mediated dysregulation in homeostatic plasticity may play an important role in the pathogenesis of altered neural function and memory deficits in the early stages of AD.

Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity.

Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear. Here we show that brief monocular deprivation during the critical period downregulates neuregulin-1(NRG1)/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons. Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells through downstream PKC-dependent activation and AMPA receptor exocytosis, thus enhancing PV neuronal inhibition to excitatory neurons. NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo. Our findings reveal molecular, cellular, and circuit mechanisms of NRG1/ErbB4 in regulating the initiation of critical period visual cortical plasticity.

[Wulst Activation in Pied Flycatcher Nestlings in Feeding Behavior Induced by Patterned Visual Stimulus].

Immunohistochemical detection of c-Fos was used to study the transcriptional activation in two higher visual centers (Wulst area and Entopallium) of 12-day-old pied flycatcher (Ficedula hypoleuca) during the realization of feeding behavior guided by patterned visual stimulus, simulating the species-specific one. Activation was compared in 4 groups of nestlings. Control group was not subjected to any experimental influence. In binocular, right-field (deprivation of the left eye) and left-filed (deprivation of the right eye) groups the vision feeding responses were provoked, reinforced and evaluated. It was shown that the visual afferentation from the right eye was more significant for the organization of early feeding behavior guided by a moving patterned visual stimulus as compared with the afferentation from the left eye. Feeding behavior induced activation of c-Fos expression only in neurons of the higher center of thalamofugal system--Wulst area. The comparison of transcriptional activation in different groups revealed the significant increase of c-Fos induction related with feeding behavior only in the left hemisphere and only in binocular and right-field groups.