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1.
Cell Rep ; 43(4): 114017, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38578827

ABSTRACT

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness, suprathreshold stimuli evoke perceptions; under anesthesia, perceptions are abolished; and during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perceptions. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia as well as during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely, in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is reliably elicited by external visual stimuli.


Subject(s)
Neurons , Wakefulness , Animals , Wakefulness/physiology , Mice , Neurons/physiology , Hallucinations/physiopathology , Male , Mice, Inbred C57BL , Ketamine/pharmacology , Photic Stimulation , Brain Waves/physiology , Visual Cortex/physiology , Brain/physiology
2.
bioRxiv ; 2023 May 23.
Article in English | MEDLINE | ID: mdl-37292587

ABSTRACT

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness stimuli evoke perceptions; under anesthesia perceptions are abolished; during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perception. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia and during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is elicited by specifically by external visual stimuli.

3.
Phys Rev Lett ; 130(24): 247401, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37390429

ABSTRACT

Contagion processes on networks, including disease spreading, information diffusion, or social behaviors propagation, can be modeled as simple contagion, i.e., as a contagion process involving one connection at a time, or as complex contagion, in which multiple interactions are needed for a contagion event. Empirical data on spreading processes, however, even when available, do not easily allow us to uncover which of these underlying contagion mechanisms is at work. We propose a strategy to discriminate between these mechanisms upon the observation of a single instance of a spreading process. The strategy is based on the observation of the order in which network nodes are infected, and on its correlations with their local topology: these correlations differ between processes of simple contagion, processes involving threshold mechanisms, and processes driven by group interactions (i.e., by "higher-order" mechanisms). Our results improve our understanding of contagion processes and provide a method using only limited information to distinguish between several possible contagion mechanisms.


Subject(s)
Reproduction , Social Behavior , Diffusion
4.
Front Chem ; 11: 1128859, 2023.
Article in English | MEDLINE | ID: mdl-36778030

ABSTRACT

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. For the virus to enter the host cell, its spike (S) protein binds to the ACE2 receptor, and the transmembrane protease serine 2 (TMPRSS2) cleaves the binding for the fusion. As part of the research on COVID-19 treatments, several Casiopeina-analogs presented here were looked at as TMPRSS2 inhibitors. Using the DFT and conceptual-DFT methods, it was found that the global reactivity indices of the optimized molecular structures of the inhibitors could be used to predict their pharmacological activity. In addition, molecular docking programs (AutoDock4, Molegro Virtual Docker, and GOLD) were used to find the best potential inhibitors by looking at how they interact with key amino acid residues (His296, Asp 345, and Ser441) in the catalytic triad. The results show that in many cases, at least one of the amino acids in the triad is involved in the interaction. In the best cases, Asp435 interacts with the terminal nitrogen atoms of the side chains in a similar way to inhibitors such as nafamostat, camostat, and gabexate. Since the copper compounds localize just above the catalytic triad, they could stop substrates from getting into it. The binding energies are in the range of other synthetic drugs already on the market. Because serine protease could be an excellent target to stop the virus from getting inside the cell, the analyzed complexes are an excellent place to start looking for new drugs to treat COVID-19.

5.
Cell Stem Cell ; 30(2): 137-152.e7, 2023 02 02.
Article in English | MEDLINE | ID: mdl-36736289

ABSTRACT

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.


Subject(s)
Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Humans , Rats , Animals , Adult , Prosencephalon , Neurons/physiology , Pluripotent Stem Cells/physiology , Retina , Organoids/metabolism , Induced Pluripotent Stem Cells/physiology , Mammals
6.
Nat Neurosci ; 26(1): 39-52, 2023 01.
Article in English | MEDLINE | ID: mdl-36424433

ABSTRACT

The brain can become transiently disconnected from the environment while maintaining vivid, internally generated experiences. This so-called 'dissociated state' can occur in pathological conditions and under the influence of psychedelics or the anesthetic ketamine (KET). The cellular and circuit mechanisms producing the dissociative state remain poorly understood. We show in mice that KET causes spontaneously active neurons to become suppressed while previously silent neurons become spontaneously activated. This switch occurs in all cortical layers and different cortical regions, is induced by both systemic and cortical application of KET and is mediated by suppression of parvalbumin and somatostatin interneuron activity and inhibition of NMDA receptors and HCN channels. Combined, our results reveal two largely non-overlapping cortical neuronal populations-one engaged in wakefulness, the other contributing to the KET-induced brain state-and may lay the foundation for understanding how the brain might become disconnected from the surrounding environment while maintaining internal subjective experiences.


Subject(s)
Ketamine , Neocortex , Mice , Animals , Ketamine/pharmacology , Neurons , Interneurons/physiology
7.
IUCrdata ; 7(Pt 6): x220627, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36339897

ABSTRACT

The title compound, (C4H12N5)4(C2H7N4O)2[V10O28]·4H2O, is a by-product obtained by reacting ammonium metavanadate(V), metformin hydro-chloride and acetic acid in the presence of sodium hypochlorite, at pH = 5. The crystal structure comprises a deca-vanadate(V) anion (V10O28)6- lying on an inversion centre in space group P , while cations and solvent water mol-ecules are placed in general positions, surrounding the anion, and forming numerous N-H⋯O and O-H⋯O hydrogen bonds. Metforminium (C4H12N5)+ and guanylurea (C2H7N4O)+ cations display the expected shape. Inter-estingly, in physiology the latter cation is known to be the main metabolite of the former one. The reported structure thus supports the role of sodium hypochlorite as an oxidizing reagent being able to degrade metformin hydro-chloride to form guanylurea.

8.
Nat Commun ; 13(1): 4754, 2022 08 13.
Article in English | MEDLINE | ID: mdl-35963850

ABSTRACT

Sensory processing is distributed among many brain regions that interact via feedforward and feedback signaling. Neuronal oscillations have been shown to mediate intercortical feedforward and feedback interactions. Yet, the macroscopic structure of the multitude of such oscillations remains unclear. Here, we show that simple visual stimuli reliably evoke two traveling waves with spatial wavelengths that cover much of the cerebral hemisphere in awake mice. 30-50 Hz feedforward waves arise in primary visual cortex (V1) and propagate rostrally, while 3-6 Hz feedback waves originate in the association cortex and flow caudally. The phase of the feedback wave modulates the amplitude of the feedforward wave and synchronizes firing between V1 and parietal cortex. Altogether, these results provide direct experimental evidence that visual evoked traveling waves percolate through the cerebral cortex and coordinate neuronal activity across broadly distributed networks mediating visual processing.


Subject(s)
Visual Cortex , Animals , Cerebral Cortex , Feedback , Mice , Photic Stimulation/methods , Visual Cortex/physiology , Visual Perception/physiology
9.
J R Soc Interface ; 19(191): 20220164, 2022 06.
Article in English | MEDLINE | ID: mdl-35730172

ABSTRACT

Computational models offer a unique setting to test strategies to mitigate the spread of infectious diseases, providing useful insights to applied public health. To be actionable, models need to be informed by data, which can be available at different levels of detail. While high-resolution data describing contacts between individuals are increasingly available, data gathering remains challenging, especially during a health emergency. Many models thus use synthetic data or coarse information to evaluate intervention protocols. Here, we evaluate how the representation of contact data might affect the impact of various strategies in models, in the realm of COVID-19 transmission in educational and work contexts. Starting from high-resolution contact data, we use detailed to coarse data representations to inform a model of SARS-CoV-2 transmission and simulate different mitigation strategies. We find that coarse data representations estimate a lower risk of superspreading events. However, the rankings of protocols according to their efficiency or cost remain coherent across representations, ensuring the consistency of model findings to inform public health advice. Caution should be taken, however, on the quantitative estimations of those benefits and costs triggering the adoption of protocols, as these may depend on data representation.


Subject(s)
COVID-19 , Communicable Diseases , COVID-19/epidemiology , Communicable Diseases/epidemiology , Humans , Models, Theoretical , SARS-CoV-2
10.
Poult Sci ; 101(7): 101903, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35580374

ABSTRACT

The objective of this study was to estimate the good-of-fitness and precision of parameters of the Gompertz-Laird, Logistic, Richards, and Von Bertalanffy growth models, using different data collection periods (DCP). Two hundred and sixty-two Mexican Creole chicks (116 females and 146 males), were individually weighed to form the following sets of data for each sex: DCP1 (weights recorded weekly from hatching to 63 d, and every 2 wk, from 63 to 133 d of age), DCP2 (weights recorded weekly from hatching to 133 d of age), DCP3 (weights recorded every third day, from hatching to 63 d, and every 14 d, from 63 to 133 d of age), and DCP4 (weights recorded every third day, from hatching to 63 d, and weekly, from 63 to 133 d of age). Data were analyzed using the NLIN procedure of SAS (Marquardt algorithm). For all growth models, the width of confidence interval (CI) of each parameter, was estimated (α = 0.05). The adjusted coefficient of determination (AR2), as well as the Akaike (AIC) and Bayesian information criteria (BIC) were used to select the best model. The higher the AR2, and the lower the width of CI, as well as the AIC and BIC values, the better the model. The Gompertz-Laird model, more frequently showed the highest AR2, and the lowest AIC and BIC values compared to the other models. Moreover, for all models, both sexes and all parameters, most confidence interval widths (all with the Gompertz-Laird model) were the lowest with DCP3 when compared to the other sets of data. In conclusion, the Gompertz-Laird model was the best provided that the chickens are weighed every third day from hatching until 63 d of age, and every 2 wk thereafter.


Subject(s)
Chickens , Models, Biological , Animals , Bayes Theorem , Body Weight , Data Collection , Female , Male
11.
Lancet Infect Dis ; 22(7): 977-989, 2022 07.
Article in English | MEDLINE | ID: mdl-35378075

ABSTRACT

BACKGROUND: Schools were closed extensively in 2020-21 to counter SARS-CoV-2 spread, impacting students' education and wellbeing. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. By estimating school-specific transmissibility, our study evaluates costs and benefits of different protocols for SARS-CoV-2 control at school. METHODS: We developed an agent-based model of SARS-CoV-2 transmission in schools. We used empirical contact data in a primary and a secondary school and data from pilot screenings in 683 schools during the alpha variant (B.1.1.7) wave in March-June, 2021, in France. We fitted the model to observed school prevalence to estimate the school-specific effective reproductive number for the alpha (Ralpha) and delta (B.1.617.2; Rdelta) variants and performed a cost-benefit analysis examining different intervention protocols. FINDINGS: We estimated Ralpha to be 1·40 (95% CI 1·35-1·45) in the primary school and 1·46 (1·41-1·51) in the secondary school during the spring wave, higher than the time-varying reproductive number estimated from community surveillance. Considering the delta variant and vaccination coverage in Europe as of mid-September, 2021, we estimated Rdelta to be 1·66 (1·60-1·71) in primary schools and 1·10 (1·06-1·14) in secondary schools. Under these conditions, weekly testing of 75% of unvaccinated students (PCR tests on saliva samples in primary schools and lateral flow tests in secondary schools), in addition to symptom-based testing, would reduce cases by 34% (95% CI 32-36) in primary schools and 36% (35-39) in secondary schools compared with symptom-based testing alone. Insufficient adherence was recorded in pilot screening (median ≤53%). Regular testing would also reduce student-days lost up to 80% compared with reactive class closures. Moderate vaccination coverage in students would still benefit from regular testing for additional control-ie, weekly testing 75% of unvaccinated students would reduce cases compared with symptom-based testing only, by 23% in primary schools when 50% of children are vaccinated. INTERPRETATION: The COVID-19 pandemic will probably continue to pose a risk to the safe and normal functioning of schools. Extending vaccination coverage in students, complemented by regular testing with good adherence, are essential steps to keep schools open when highly transmissible variants are circulating. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Horizon Europe Framework Programme, Agence Nationale de la Recherche, ANRS-Maladies Infectieuses Émergentes.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Child , Humans , Pandemics/prevention & control , SARS-CoV-2/genetics , Schools , Vaccination
12.
J Neurosci ; 41(37): 7797-7812, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34321313

ABSTRACT

The spatial organization and dynamic interactions between excitatory and inhibitory synaptic inputs that define the receptive field (RF) of simple cells in the cat primary visual cortex (V1) still raise the following paradoxical issues: (1) stimulation of simple cells in V1 with drifting gratings supports a wiring schema of spatially segregated sets of excitatory and inhibitory inputs activated in an opponent way by stimulus contrast polarity and (2) in contrast, intracellular studies using flashed bars suggest that although ON and OFF excitatory inputs are indeed segregated, inhibitory inputs span the entire RF regardless of input contrast polarity. Here, we propose a biologically detailed computational model of simple cells embedded in a V1-like network that resolves this seeming contradiction. We varied parametrically the RF-correlation-based bias for excitatory and inhibitory synapses and found that a moderate bias of excitatory neurons to synapse onto other neurons with correlated receptive fields and a weaker bias of inhibitory neurons to synapse onto other neurons with anticorrelated receptive fields can explain the conductance input, the postsynaptic membrane potential, and the spike train dynamics under both stimulation paradigms. This computational study shows that the same structural model can reproduce the functional diversity of visual processing observed during different visual contexts.SIGNIFICANCE STATEMENT Identifying generic connectivity motives in cortical circuitry encoding for specific functions is crucial for understanding the computations implemented in the cortex. Indirect evidence points to correlation-based biases in the connectivity pattern in V1 of higher mammals, whereby excitatory and inhibitory neurons preferentially synapse onto neurons respectively with correlated and anticorrelated receptive fields. A recent intracellular study questions this push-pull hypothesis, failing to find spatial anticorrelation patterns between excitation and inhibition across the receptive field. We present here a spiking model of V1 that integrates relevant anatomic and physiological constraints and shows that a more versatile motif of correlation-based connectivity with selectively tuned excitation and broadened inhibition is sufficient to account for the diversity of functional descriptions obtained for different classes of stimuli.


Subject(s)
Models, Neurological , Neural Inhibition/physiology , Neurons/physiology , Synaptic Transmission/physiology , Visual Cortex/physiology , Visual Pathways/physiology , Action Potentials/physiology , Animals , Cats , Synapses/physiology , Visual Perception/physiology
13.
Elife ; 102021 02 04.
Article in English | MEDLINE | ID: mdl-33538694

ABSTRACT

Three rules govern the connectivity between neurons in the thalamus and inhibitory neurons in the visual cortex of rabbits.


Subject(s)
Visual Cortex , Animals , Neurons , Rabbits , Thalamus
14.
Rev. chil. dermatol ; 36(3): 108-110, 2020. ilus
Article in Spanish | LILACS | ID: biblio-1400447

ABSTRACT

Una de las infecciones virales más comunes -sobretodo en personas de mayor edad- es el Herpes Zóster (HZ). Su característica clínica, hace sospechar al médico de forma temprana, para otorgar un tratamiento adecuado y oportuno. Dentro de las complicaciones más frecuentes se encuentran las sensitivas, como la neuralgia postherpética.1 Sin embargo, existen un grupo de complicaciones motoras de menor incidencia, como lo es la Pseudohernia abdominal. Ésta corresponde a una paresia segmentaria, que se manifiesta como una protrusión de la pared abdominal sin un defecto real, que aumenta con maniobras de valsalva.1 Generalmente se puede presentar en hombres, mayores de 60 años, inmunosuprimidos o con neoplasias hematológicas.1,2,3 El diagnóstico es clínico, aunque se puede confirmar con estudio imagenológico, que evidencie una musculatura de la pared abdominal adelgazada con respecto a la contralateral y que descarta un orificio herniario por un defecto estructural. 2 La electromiografía también puede jugar un rol al evidenciar anormalidades en la conducción nerviosa. 2 La pseudohernia por HZ tiene un buen pronóstico en la mayoría de los pacientes con recuperación completa: entre 2-18 meses. 3 Su principal riesgo es la pseudobstrucción intestinal, que se puede manifestar como constipación.2,4 En el siguiente reporte de caso, se analiza a la pseudohernia abdominal como complicación motora infrecuente del HZ y sus características.


One of the most common viral infections -especially in elderly- is Herpes Zoster (HZ). Its clinical characteristic makes the doctor suspect early, to grant adequate and timely treatment. Among the most frequent complications are the sensitive ones, such as postherpetic neuralgia1 . However, there is a group of motor complications of lower incidence, such as abdominal pseudohernia. This corresponds to a segmental paresis, which manifests as a protrusion of the abdominal wall without a real defect that increases with valsalva maneuvers1 . It can generally present in men, older than 60 years, immunosuppressed or with hematological neoplasms1,2,3, The diagnosis is clinical, although it can be confirmed with an imaging study, which shows a thinner abdominal wall musculature with regard to the contralateral wall, and which rules out a hernial orifice due to a structural defect2 . Electromyography can also play a role in show abnormalities in nerve conduction2 . HZ pseudohernia has a good prognosis in most patients with complete recovery: between 2-18 months.3 Its main risk is intestinal pseudoobstruction, which can manifest as constipation2,4. In the following case report, abdominal pseudohernia is analyzed as a rare motor complication of HZ and its characteristics.


Subject(s)
Humans , Male , Aged , Abdominal Wall , Herpes Zoster/complications , Herpes Zoster/diagnostic imaging
15.
Front Syst Neurosci ; 13: 19, 2019.
Article in English | MEDLINE | ID: mdl-31139058

ABSTRACT

Previous research demonstrates that the underlying state of the brain influences how sensory stimuli are processed. Canonically, the state of the brain has been defined by quantifying the spectral characteristics of spontaneous fluctuations in local field potentials (LFP). Here, we utilized isoflurane and propofol anesthesia to parametrically alter the spectral state of the murine brain. With either drug, we produce slow wave activity, with low anesthetic doses, or burst suppression, with higher doses. We find that while spontaneous LFP oscillations were similar, the average visual-evoked potential (VEP) was always smaller in amplitude and shorter in duration under propofol than under comparable doses of isoflurane. This diminished average VEP results from increased trial-to-trial variability in VEPs under propofol. One feature of single trial VEPs that was consistent in all animals was visual-evoked gamma band oscillation (20-60 Hz). This gamma band oscillation was coherent between trials in the early phase (<250 ms) of the visual evoked potential under isoflurane. Inter trial phase coherence (ITPC) of gamma oscillations was dramatically attenuated in the same propofol anesthetized mice despite similar spontaneous oscillations in the LFP. This suggests that while both anesthetics lead to loss of consciousness (LOC), elicit slow oscillations and burst suppression, only the isoflurane permits phase resetting of gamma oscillations by visual stimuli. These results demonstrate that accurate characterization of a brain state must include both spontaneous as well as stimulus-induced perturbations of brain activity.

16.
Elife ; 82019 04 29.
Article in English | MEDLINE | ID: mdl-31032799

ABSTRACT

The thalamocortical synapse of the visual system has been central to our understanding of sensory computations in the cortex. Although we have a fair understanding of the functional properties of the pre and post-synaptic populations, little is known about their synaptic properties, particularly in vivo. We used simultaneous recordings in LGN and V1 in cat in vivo to characterize the dynamic properties of thalamocortical synaptic transmission in monosynaptically connected LGN-V1 neurons. We found that thalamocortical synapses in vivo are unreliable, highly variable and exhibit short-term plasticity. Using biologically constrained models, we found that variable and unreliable synapses serve to increase cortical firing by means of increasing membrane fluctuations, similar to high conductance states. Thus, synaptic variability and unreliability, rather than acting as system noise, do serve a computational function. Our characterization of LGN-V1 synaptic properties constrains existing mathematical models, and mechanistic hypotheses, of a fundamental circuit in computational neuroscience.


Subject(s)
Synapses/physiology , Synaptic Transmission/physiology , Thalamus/physiology , Visual Cortex/physiology , Animals , Cats , Excitatory Postsynaptic Potentials/physiology , Interneurons , Male , Neuronal Plasticity/physiology , Neurons/physiology , Visual Fields
17.
J Neurophysiol ; 119(6): 2068-2081, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29488838

ABSTRACT

New devices that use targeted electrical stimulation to treat refractory localization-related epilepsy have shown great promise, although it is not well known which targets most effectively prevent the initiation and spread of seizures. To better understand how the brain transitions from healthy to seizing on a local scale, we induced focal epileptiform activity in the visual cortex of five anesthetized cats with local application of the GABAA blocker picrotoxin while simultaneously recording local field potentials on a high-resolution electrocorticography array and laminar depth probes. Epileptiform activity appeared in the form of isolated events, revealing a consistent temporal pattern of ictogenesis across animals with interictal events consistently preceding the appearance of seizures. Based on the number of spikes per event, there was a natural separation between seizures and shorter interictal events. Two distinct spatial regions were seen: an epileptic focus that grew in size as activity progressed, and an inhibitory surround that exhibited a distinct relationship with the focus both on the surface and in the depth of the cortex. Epileptiform activity in the cortical laminae was seen concomitant with activity on the surface. Focus spikes appeared earlier on electrodes deeper in the cortex, suggesting that deep cortical layers may be integral to recruiting healthy tissue into the epileptic network and could be a promising target for interventional devices. Our study may inform more effective therapies to prevent seizure generation and spread in localization-related epilepsies. NEW & NOTEWORTHY We induced local epileptiform activity and recorded continuous, high-resolution local field potentials from the surface and depth of the visual cortex in anesthetized cats. Our results reveal a consistent pattern of ictogenesis, characterize the spatial spread of the epileptic focus and its relationship with the inhibitory surround, and show that focus activity within events appears earliest in deeper cortical layers. These findings have potential implications for the monitoring and treatment of refractory epilepsy.


Subject(s)
Cortical Excitability , Drug Resistant Epilepsy/physiopathology , Neocortex/physiology , Animals , Cats , Male , Neocortex/physiopathology
18.
J Neurosci ; 38(3): 595-612, 2018 01 17.
Article in English | MEDLINE | ID: mdl-29196320

ABSTRACT

Inhibition in thalamorecipient layer 4 simple cells of primary visual cortex is believed to play important roles in establishing visual response properties and integrating visual inputs across their receptive fields (RFs). Simple cell RFs are characterized by nonoverlapping, spatially restricted subregions in which visual stimuli can either increase or decrease the firing rate of the cell, depending on contrast. Inhibition is believed to be triggered exclusively from visual stimulation of individual RF subregions. However, this view is at odds with the known anatomy of layer 4 interneurons in visual cortex and differs from recent findings in mouse visual cortex. Here we show with in vivo intracellular recordings in cats that while excitation is restricted to RF subregions, inhibition spans the width of simple cell RFs. Consequently, excitatory stimuli within a subregion concomitantly drive excitation and inhibition. Furthermore, we found that the distribution of inhibition across the RF is stronger toward OFF subregions. This inhibitory OFF-subregion bias has a functional consequence on spatial integration of inputs across the RF. A model based on the known anatomy of layer 4 demonstrates that the known proportion and connectivity of inhibitory neurons in layer 4 of primary visual cortex is sufficient to explain broad inhibition with an OFF-subregion bias while generating a variety of phase relations, including antiphase, between excitation and inhibition in response to drifting gratings.SIGNIFICANCE STATEMENT The wiring of excitatory and inhibitory neurons in cortical circuits is key to determining the response properties in sensory cortex. In the visual cortex, the first cells that receive visual input are simple cells in layer 4. The underlying circuitry responsible for the response properties of simple cells is not yet known. In this study, we challenge a long-held view concerning the pattern of inhibitory input and provide results that agree with current known anatomy. We show here that inhibition is evoked broadly across the receptive fields of simple cells, and we identify a surprising bias in inhibition within the receptive field. Our findings represent a step toward a unified view of inhibition across different species and sensory systems.


Subject(s)
Interneurons/cytology , Interneurons/physiology , Models, Neurological , Neural Inhibition/physiology , Visual Cortex/cytology , Visual Cortex/physiology , Animals , Cats , Male , Photic Stimulation
19.
J Physiol ; 596(3): 515-534, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29265375

ABSTRACT

KEY POINTS: Rodents explore their immediate environment using their whiskers. Such exploration leads to micromotions, which contain many high-frequency (50-200 Hz) components. High-frequency whisker motion is represented faithfully in the temporal structure of the spike trains of trigeminal neurons. However, the representation of high-frequency sensory inputs in cortex is not fully understood. By combining extracellular and intracellular recordings in the rat somatosensory cortex and thalamus, we show that high-frequency sensory inputs, either sinusoidal or white noise, elicit internally generated gamma (20-60 Hz) band oscillations in cortical networks. Gamma oscillations modulate cortical spike probability while preserving sub-millisecond phase relations with high-frequency sensory inputs. Consequently, our results indicate that millisecond precision stimulus-locked spiking activity and sensory-induced gamma oscillation can constitute independent multiplexed coding schemes at the single-cell level. ABSTRACT: In the natural environment, tactile exploration often leads to high-frequency vibrations at the level of the sensory organs. Single-unit recordings of cortical neurons have pointed towards either a rate or a temporal code for representing high-frequency tactile signals. In cortical networks, sensory processing results from the interaction between feedforward inputs relayed from the thalamus and internally generated activity. However, how the emergent activity represents high-frequency sensory input is not fully understood. Using multisite single-unit, local field potential and intracellular recordings in the somatosensory cortex and thalamus of lightly sedated male rats, we measured neuronal responses evoked by sinusoidal and band-pass white noise whisker stimulation at frequencies that encompass those observed during texture exploration (50-200 Hz). We found that high-frequency sensory inputs relayed from the thalamus elicit both sub-millisecond stimulus-locked responses and internally generated gamma (20-60 Hz) band oscillations in cortical networks. Gamma oscillations modulate spike probability while preserving sub-millisecond phase relations with sensory inputs. Therefore, precise stimulus-locked spiking activity and sensory-induced gamma oscillations can constitute independent multiplexed coding schemes at the single-cell level.


Subject(s)
Action Potentials , Evoked Potentials, Somatosensory , Neurons/physiology , Noise , Somatosensory Cortex/physiology , Vibrissae/physiology , Animals , Male , Neurons/cytology , Rats , Rats, Sprague-Dawley , Somatosensory Cortex/cytology , Vibration
20.
J Neurosci ; 37(21): 5250-5262, 2017 05 24.
Article in English | MEDLINE | ID: mdl-28438969

ABSTRACT

Seminal studies of the thalamocortical circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, thalamocortical synaptic properties remain poorly understood. We used paired recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex (V1), to provide the first in vivo characterization of sensory-driven thalamocortical potentials in V1. The amplitudes of EPSPs we characterized were smaller than those previously reported in vitro Consistent with prior findings, connected LGN-V1 pairs were only found when their receptive fields (RFs) overlapped, and the probability of connection increased steeply with degree of RF overlap and response similarity. However, surprisingly, we found no relationship between EPSP amplitudes and the similarity of RFs or responses, suggesting different connectivity models for intracortical and thalamocortical circuits. Putative excitatory regular-spiking (RS) and inhibitory fast-spiking (FS) V1 cells had similar EPSP characteristics, showing that in the visual system, feedforward excitation and inhibition are driven with equal strength by the thalamus. Similar to observations in the somatosensory cortex, FS V1 cells received less specific input from LGN. Finally, orientation tuning in V1 was not inherited from single presynaptic LGN cells, suggesting that it must emerge exclusively from the combined input of all presynaptic LGN cells. Our results help to decipher early visual encoding circuits and have immediate utility in providing physiological constraints to computational models of the visual system.SIGNIFICANCE STATEMENT To understand how the brain encodes the visual environment, we must understand the transfer of visual signals between various regions of the brain. Therefore, understanding synaptic dynamics is critical to our understanding of sensory encoding. This study provides the first characterization of visually evoked synaptic potentials between the visual thalamus and visual cortex in an intact animal. To record these potentials, we simultaneously recorded the extracellular potential of presynaptic thalamic cells and the intracellular potential of postsynaptic cortical cells in input layers of primary visual cortex. Our characterization of synaptic potentials in vivo disagreed with prior findings in vitro This study will increase our understanding of thalamocortical circuits and will improve computational models of visual encoding.


Subject(s)
Synapses/physiology , Thalamus/physiology , Visual Cortex/physiology , Animals , Cats , Evoked Potentials, Visual , Excitatory Postsynaptic Potentials , Male , Thalamus/cytology , Visual Cortex/cytology , Visual Fields
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