RESUMO
The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of saccades toward a visual target. On the basis of the organization of their efferences to the premotor burst neurons and the bilateral control of saccades, the hypothesis was proposed that the same unbalanced activity accounts for the dysmetria of all saccades during cFN unilateral inactivation, regardless of whether the saccade is horizontal, oblique, or vertical. We further tested this hypothesis by studying, in two head-restrained macaques, the effects of unilaterally inactivating the caudal fastigial nucleus on saccades toward a target moving vertically with a constant, increasing or decreasing speed. After local muscimol injection, vertical saccades were deviated horizontally toward the injected side with a magnitude that increased with saccade size. The ipsipulsion indeed depended on the tested target speed but not its instantaneous value because it did not increase (decrease) when the target accelerated (decelerated). By subtracting the effect on contralesional horizontal saccades from the effect on ipsilesional ones, we found that the net bilateral effect on horizontal saccades was strongly correlated with the effect on vertical saccades. We explain how this correlation corroborates the bilateral hypothesis and provide arguments against the suggestion that the instantaneous saccade velocity would somehow be "encoded" by the discharge of Purkinje cells in the oculomotor vermis.NEW & NOTEWORTHY Besides causing dysmetric horizontal saccades, unilateral inactivation of caudal fastigial nucleus causes an ipsipulsion of vertical saccades. This study is the first to quantitatively describe this ipsipulsion during saccades toward a moving target. By subtracting the effects on contralesional (hypometric) and ipsilesional (hypermetric) horizontal saccades, we find that this net bilateral effect is strongly correlated with the ipsipulsion of vertical saccades, corroborating the suggestion that a common disorder affects all saccades.
Assuntos
Núcleos Cerebelares/fisiologia , Agonistas de Receptores de GABA-A/farmacologia , Percepção de Movimento/fisiologia , Muscimol/farmacologia , Transtornos da Motilidade Ocular/fisiopatologia , Movimentos Sacádicos/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Núcleos Cerebelares/efeitos dos fármacos , Modelos Animais de Doenças , Tecnologia de Rastreamento Ocular , Agonistas de Receptores de GABA-A/administração & dosagem , Macaca mulatta , Masculino , Percepção de Movimento/efeitos dos fármacos , Muscimol/administração & dosagem , Transtornos da Motilidade Ocular/induzido quimicamente , Movimentos Sacádicos/efeitos dos fármacosRESUMO
How neurons filter and integrate their complex patterns of synaptic inputs is central to their role in neural information processing. Synaptic filtering and integration are shaped by the frequency-dependent neuronal membrane impedance. Using single and dual dendritic recordings in vivo, pharmacology, and computational modeling, we characterized the membrane impedance of a collision detection neuron in the grasshopper Schistocerca americana. This neuron, the lobula giant movement detector (LGMD), exhibits consistent impedance properties across frequencies and membrane potentials. Two common active conductances gH and gM, mediated respectively by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and by muscarine-sensitive M-type K+ channels, promote broadband integration with high temporal precision over the LGMD's natural range of membrane potentials and synaptic input frequencies. Additionally, we found that a model based on the LGMD's branching morphology increased the gain and decreased the delay associated with the mapping of synaptic input currents to membrane potential. More generally, this was true for a wide range of model neuron morphologies, including those of neocortical pyramidal neurons and cerebellar Purkinje cells. These findings show the unexpected role played by two widespread active conductances and by dendritic morphology in shaping synaptic integration.NEW & NOTEWORTHY Neuronal filtering and integration of synaptic input patterns depend on the electrochemical properties of dendrites. We used an identified collision detection neuron in grasshoppers to examine how its morphology and two conductances affect its membrane impedance in relation to the computations it performs. The neuronal properties examined are ubiquitous and therefore promote a general understanding of neuronal computations, including those in the human brain.
Assuntos
Dendritos/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Percepção de Movimento/fisiologia , Neurônios/fisiologia , Animais , Impedância Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Gafanhotos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/antagonistas & inibidores , Modelos Biológicos , Percepção de Movimento/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologiaRESUMO
While neonicotinoid insecticides impair visually guided behaviours, the effects of their metabolites are unknown and measurements of environmental concentrations of neonicotinoids, typically lower than those required to elicit toxic effects, tend to exclude metabolites. Here we examined the contributions of imidacloprid and two of its metabolites, imidacloprid-olefin and 5-hydroxy-imidacloprid, on neural conduction velocity, visual motion detection and flight in the locust (Locusta migratoria) using a combination of electrophysiological and behavioural assays. We show reduced visual motion detection and impaired flight behaviour following treatment of metabolite concentrations equal to sublethal doses of the parent compound. Additionally, we show for the first time that imidacloprid and its metabolites result in a decrease in conduction velocity along an unmyelinated axon. We suggest that secondary effects of the insecticide on the biophysical properties of the axon may result in decreased neural conduction. As these metabolites display neurotoxicity similar to the parent compound they should be considered when quantifying environmental concentrations.
Assuntos
Voo Animal/efeitos dos fármacos , Inseticidas/toxicidade , Locusta migratoria/efeitos dos fármacos , Percepção de Movimento/efeitos dos fármacos , Neonicotinoides/toxicidade , Condução Nervosa/efeitos dos fármacos , Nitrocompostos/toxicidade , Animais , Inseticidas/metabolismo , Locusta migratoria/fisiologia , Masculino , Neonicotinoides/metabolismo , Nitrocompostos/metabolismoRESUMO
Preliminary studies have suggested that γ-aminobutyric acid type A (GABAA) receptors, and potentially the GABAA α5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, and these studies did not compare findings across different species. We measured both total GABAA and GABAA α5 receptor availability in two positron emission tomography imaging studies. We used the tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control individuals without ASD. All participants were free of medications. We also performed autoradiography, using the same tracers, in three mouse models of ASD: the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a 16p11.2 deletion. We found no differences in GABAA receptor or GABAA α5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA α5 subunit availability in any of the three mouse models. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task. Our data suggest that GABAA receptor availability may be normal in adults with ASD, although GABA signaling may be functionally impaired.
Assuntos
Transtorno do Espectro Autista/metabolismo , Receptores de GABA-A/metabolismo , Adulto , Animais , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/patologia , Azidas/farmacologia , Comportamento , Benzodiazepinas/farmacologia , Radioisótopos de Carbono , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Flumazenil/farmacologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Humanos , Masculino , Camundongos , Percepção de Movimento/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Subunidades Proteicas/metabolismo , Análise e Desempenho de TarefasRESUMO
RATIONALE: Cannabis use impairs visual attention; however, it is unclear whether cannabis use also impairs low level visual processing or whether low level visual deficits can be related to lower dopaminergic functioning found in cannabis users. OBJECTIVES: To investigate whether spatiotemporal contrast sensitivity and motion discrimination under normal and low luminance conditions differ in cannabis users and non-users. METHODS: Control (n = 20) and cannabis (n = 21) participants completed a visual acuity test, a saliva test and self-report measures. Spatial and temporal contrast thresholds, motion coherence thresholds for translational and radial motion and the spontaneous eye blink rate were then collected. RESULTS: Cannabis users showed decreased spatial contrast sensitivity under low luminance conditions and increased motion coherence thresholds under all luminance levels tested compared to non-users. No differences in temporal contrast sensitivity were found between the groups. Frequency of cannabis use correlated significantly and negatively with contrast sensitivity, both spatial and temporal, in the cannabis group and higher motion coherence thresholds for radial motion were also associated with more frequent cannabis use in this group. The eye blink rate was significantly lower in cannabis users compared to non-users. CONCLUSIONS: The present study shows that cannabis use is associated with deficits in low level visual processing. Such deficits are suggested to relate to lower dopamine, in a similar manner as in clinical populations. The implications for driving safety under reduced visibility (e.g. night) in abstaining cannabis users are discussed.
Assuntos
Piscadela/efeitos dos fármacos , Sensibilidades de Contraste/efeitos dos fármacos , Uso da Maconha/efeitos adversos , Uso da Maconha/psicologia , Percepção de Movimento/efeitos dos fármacos , Adolescente , Adulto , Atenção/efeitos dos fármacos , Atenção/fisiologia , Piscadela/fisiologia , Sensibilidades de Contraste/fisiologia , Feminino , Alucinógenos/administração & dosagem , Alucinógenos/efeitos adversos , Humanos , Masculino , Uso da Maconha/metabolismo , Percepção de Movimento/fisiologia , Estimulação Luminosa/métodos , Saliva/metabolismo , Limiar Sensorial/efeitos dos fármacos , Limiar Sensorial/fisiologia , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Serotonergic innervation of sensory areas is found ubiquitously across the central nervous system of vertebrates. Here, we used a system's level approach to investigate the role of serotonin on processing motion stimuli in the electrosensory system of the weakly electric fish Apteronotus albifrons. We found that exogenous serotonin application increased the firing activity of pyramidal neural responses to both looming and receding motion. Separating spikes belonging to bursts from those that were isolated revealed that this effect was primarily due to increased burst firing. Moreover, when investigating whether firing activity during stimulation could be discriminated from baseline (i.e., in the absence of stimulation), we found that serotonin increased stimulus discriminability only for some stimuli. This is because increased burst firing was most prominent for these. Further, the effects of serotonin were highly heterogeneous, with some neurons displaying large while others instead displaying minimal changes in responsiveness following serotonin application. Further analysis revealed that serotonin application had the greatest effect on neurons with low baseline firing rates and little to no effect on neurons with high baseline firing rates. Finally, the effects of serotonin on sensory neuron responses were largely independent of object velocity. Our results therefore reveal a novel function for the serotonergic system in selectively enhancing discriminability for motion stimuli.
Assuntos
Órgão Elétrico/fisiologia , Percepção de Movimento/fisiologia , Células Piramidais/fisiologia , Serotonina/fisiologia , Potenciais de Ação , Animais , Peixe Elétrico , Órgão Elétrico/efeitos dos fármacos , Feminino , Masculino , Percepção de Movimento/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/administração & dosagemRESUMO
Background: Perceptual decision making is the process through which available sensory information is gathered and processed to guide our choices. However, the neuropsychopharmacological basis of this important cognitive function is largely elusive. Yet, theoretical considerations suggest that the dopaminergic system may play an important role. Methods: In a double-blind, randomized, placebo-controlled study design, we examined the effect of methylphenidate in 2 dosages (0.25 mg/kg and 0.5 mg/kg body weight) in separate groups of healthy young adults. We used a moving dots task in which the coherency of the direction of moving dots stimuli was manipulated in 3 levels (5%, 15%, and 35%). Drift diffusion modelling was applied to behavioral data to capture subprocesses of perceptual decision making. Results: The findings show that only the drift rate (v), reflecting the efficiency of sensory evidence accumulation, but not the decision criterion threshold (a) or the duration of nondecisional processes (Ter), is affected by methylphenidate vs placebo administration. Compared with placebo, administering 0.25 mg/kg methylphenidate increased v, but only in the 35% coherence condition. Administering 0.5 mg/kg methylphenidate did not induce modulations. Conclusions: The data suggest that dopamine selectively modulates the efficacy of evidence accumulation during perceptual decision making. This modulation depends on 2 factors: (1) the degree to which the dopaminergic system is modulated using methylphenidate (i.e., methylphenidate dosage) and (2) the signal-to-noise ratio of the visual information. Dopamine affects sensory evidence accumulation only when dopamine concentration is not shifted beyond an optimal level and the incoming information is less noisy.
Assuntos
Tomada de Decisões/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Metilfenidato/farmacologia , Percepção de Movimento/efeitos dos fármacos , Reconhecimento Visual de Modelos/fisiologia , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Inibidores da Captação de Dopamina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Adulto JovemRESUMO
Vestibulo-ocular reflexes (VOR) are mediated by three-neuronal brainstem pathways that transform semicircular canal and otolith sensory signals into motor commands for the contraction of spatially specific sets of eye muscles. The vestibular excitation and inhibition of extraocular motoneurons underlying this reflex is reciprocally organized and allows coordinated activation of particular eye muscles and concurrent relaxation of their antagonistic counterparts. Here, we demonstrate in isolated preparations of Xenopus laevis tadpoles that the discharge modulation of superior oblique motoneurons during cyclic head motion derives from an alternating excitation and inhibition. The latter component is mediated exclusively by GABA, at variance with the glycinergic inhibitory component in lateral rectus motoneurons. The different pharmacological profile of the inhibition correlates with rhombomere-specific origins of vestibulo-ocular projection neurons and the complementary segmental abundance of GABAergic and glycinergic vestibular neurons. The evolutionary conserved rhombomeric topography of vestibulo-ocular projections makes it likely that a similar pharmacological organization of inhibitory VOR neurons as reported here for anurans is also implemented in mammalian species including humans.
Assuntos
Neurônios Motores/efeitos dos fármacos , Inibição Neural/efeitos dos fármacos , Neurotransmissores/farmacologia , Músculos Oculomotores/inervação , Reflexo Vestíbulo-Ocular/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Glicina/metabolismo , Movimentos da Cabeça/efeitos dos fármacos , Movimentos da Cabeça/fisiologia , Larva , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Neurônios Motores/fisiologia , Inibição Neural/fisiologia , Piridazinas/farmacologia , Reflexo Vestíbulo-Ocular/fisiologia , Canais Semicirculares/efeitos dos fármacos , Canais Semicirculares/fisiologia , Estricnina/farmacologia , Tegmento Mesencefálico/efeitos dos fármacos , Tegmento Mesencefálico/fisiologia , Xenopus laevis , Ácido gama-Aminobutírico/metabolismoRESUMO
Among the serious consequences of alcohol abuse is the reduced ability to process visual information. Diminished vision from excessive consumption of alcohol has been implicated in industrial, home, and automobile accidents. Alcohol is also generally recognized as an inhibitor in the brain by potentiating GABA-ergic transmission. In this study, we focused on visual motion processing and explored whether moderate alcohol intoxication induced changes in inhibitory mediated motion repulsion in a center-surround configuration. We conducted a double-blind, placebo-controlled, within-subjects study on the effect of alcohol on visual motion repulsion. Each subject underwent three experimental conditions (no alcohol, placebo and moderate alcohol) on separate days. The order of the placebo and moderate alcohol conditions was counterbalanced. The results showed that the effects of the surround context on the perception of the center motion direction were similar in both the sober (no alcohol) and placebo conditions. However, contextual modulations were significantly stronger during intoxication compared to both the sober and placebo conditions. These results demonstrate that moderate alcohol consumption is associated with altered neural function in visual cortical areas and that motion repulsion deficits might reflect the inhibitory effects of alcohol on the central nervous system.
Assuntos
Intoxicação Alcoólica/patologia , Álcoois/administração & dosagem , Álcoois/efeitos adversos , Percepção de Movimento/efeitos dos fármacos , Adulto , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Placebos/administração & dosagem , Córtex Visual/efeitos dos fármacos , Córtex Visual/fisiologia , Adulto JovemRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder pathologically characterized by a selective loss of dopaminergic neurons in the substantia nigra. In previous studies, greater attention was paid to impairments in motor disturbances in contrast to impairments of cognitive function in PD that was often ignored. In present study, a duration discrimination paradigm was used to assess global and local biological motion (BM) perception in healthy controls(HCs) and PD patients with and without dopamine substitution treatment (DST). Biological motion sequences and inanimate motion sequences (inverted BM sequences) were sequentially presented on a screen. Observers were required to verbally make a 2-alternative forced-choice to indicate whether the first or second interval appeared longer. The stimuli involved global and local BM sequences. Statistical analyses were conducted on points of subjective equality (PSE). We found significant differences between untreated PD patients and HCs as well as differences between global and local BM conditions. PD patients have a deficit in both global and local BM perception. Nevertheless, these two BM conditions can be improved under DST. Our data indicates that BM perception may be damaged in PD patients and dopaminergic medication is conducive to maintain the BM perception in PD patients.
Assuntos
Dopaminérgicos/uso terapêutico , Percepção de Movimento/fisiologia , Doença de Parkinson/tratamento farmacológico , Idoso , Estudos de Casos e Controles , Dopaminérgicos/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/efeitos dos fármacos , Testes Neuropsicológicos , Doença de Parkinson/psicologiaRESUMO
UNLABELLED: When processing sensory signals, the brain must account for noise, both noise in the stimulus and that arising from within its own neuronal circuitry. Dopamine receptor activation is known to enhance both visual cortical signal-to-noise-ratio (SNR) and visual perceptual performance; however, it is unknown whether these two dopamine-mediated phenomena are linked. To assess this, we used single-pulse transcranial magnetic stimulation (TMS) applied to visual cortical area V5/MT to reduce the SNR focally and thus disrupt visual motion discrimination performance to visual targets located in the same retinotopic space. The hypothesis that dopamine receptor activation enhances perceptual performance by improving cortical SNR predicts that dopamine activation should antagonize TMS disruption of visual perception. We assessed this hypothesis via a double-blinded, placebo-controlled study with the dopamine receptor agonists cabergoline (a D2 agonist) and pergolide (a D1/D2 agonist) administered in separate sessions (separated by 2 weeks) in 12 healthy volunteers in a William's balance-order design. TMS degraded visual motion perception when the evoked phosphene and the visual stimulus overlapped in time and space in the placebo and cabergoline conditions, but not in the pergolide condition. This suggests that dopamine D1 or combined D1 and D2 receptor activation enhances cortical SNR to boost perceptual performance. That local visual cortical excitability was unchanged across drug conditions suggests the involvement of long-range intracortical interactions in this D1 effect. Because increased internal noise (and thus lower SNR) can impair visual perceptual learning, improving visual cortical SNR via D1/D2 agonist therapy may be useful in boosting rehabilitation programs involving visual perceptual training. SIGNIFICANCE STATEMENT: In this study, we address the issue of whether dopamine activation improves visual perception despite increasing sensory noise in the visual cortex. We show specifically that dopamine D1 (or combined D1/D2) receptor activation enhances the cortical signal-to-noise-ratio to boost perceptual performance. Together with the previously reported effects of dopamine upon brain plasticity and learning (Wolf et al., 2003; Hansen and Manahan-Vaughan, 2014), our results suggest that combining rehabilitation with dopamine agonists could enhance both the saliency of the training signal and the long-term effects on brain plasticity to boost rehabilitation regimens for brain injury.
Assuntos
Dopamina/metabolismo , Percepção de Movimento/fisiologia , Ruído , Córtex Visual/fisiologia , Adulto , Análise de Variância , Cabergolina , Domperidona/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Ergolinas/farmacologia , Feminino , Humanos , Masculino , Movimento (Física) , Percepção de Movimento/efeitos dos fármacos , Estimulação Luminosa , Prolactina/metabolismo , Razão Sinal-Ruído , Estimulação Magnética Transcraniana , Córtex Visual/efeitos dos fármacos , Adulto JovemRESUMO
INTRODUCTION: Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. METHODS: Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). RESULTS: There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DISCUSSION: The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers.
Assuntos
Lobo Frontal/fisiologia , Metilfenidato/administração & dosagem , Nicotina/administração & dosagem , Desempenho Psicomotor/fisiologia , Acompanhamento Ocular Uniforme/efeitos dos fármacos , Acompanhamento Ocular Uniforme/fisiologia , Campos Visuais/fisiologia , Mapeamento Encefálico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Lobo Frontal/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Nootrópicos/administração & dosagem , Efeito Placebo , Desempenho Psicomotor/efeitos dos fármacos , Resultado do Tratamento , Campos Visuais/efeitos dos fármacos , Adulto JovemRESUMO
Strenuous exercise can result in an inability of the central nervous system to drive skeletal muscle effectively, a phenomenon known as central fatigue. The impact of central fatigue on the oculomotor system is currently unexplored. Fatigue that originates in the central nervous system may be related to perturbations in the synthesis and metabolism of several neurotransmitters. In this study we examine central fatigue in the oculomotor system after prolonged exercise. The involvement of central neurotransmission was explored by administering caffeine during exercise. Within a double-blind, randomized, repeated measures, crossover design, 11 cyclists consumed a placebo or caffeine solution during 180 min of stationary cycling. Saccadic eye movements were measured using infra-red oculography. Exercise decreased saccade velocity by 8% (placebo trial). This effect was reversed by caffeine, whereby velocity was increased by 11% after exercise. A non-oculomotor perceptual task (global motion processing) was unaffected by exercise. The human oculomotor system is impaired by strenuous exercise of the locomotor system. Caffeine exerts a protective effect on oculomotor control, which could be related to up-regulated central neurotransmission. In addition, cortical processes supporting global motion perception appear to be robust to fatigue.
Assuntos
Cafeína/administração & dosagem , Exercício Físico , Movimentos Oculares/efeitos dos fármacos , Fadiga/fisiopatologia , Percepção de Movimento/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Adulto , Feminino , Humanos , MasculinoRESUMO
Multisensory convergence of visual and vestibular signals has been observed within a network of cortical areas involved in representing heading. Vestibular-dominant heading tuning has been found in the macaque parietoinsular vestibular cortex (PIVC) and the adjacent visual posterior sylvian (VPS) area, whereas relatively balanced visual/vestibular tuning was encountered in the ventral intraparietal (VIP) area and visual-dominant tuning was found in the dorsal medial superior temporal (MSTd) area. Although the respective functional roles of these areas remain unclear, perceptual deficits in heading discrimination following reversible chemical inactivation of area MSTd area suggested that areas with vestibular-dominant heading tuning also contribute to behavior. To explore the roles of other areas in heading perception, muscimol injections were used to reversibly inactivate either the PIVC or the VIP area bilaterally in macaques. Inactivation of the anterior PIVC increased psychophysical thresholds when heading judgments were based on either optic flow or vestibular cues, although effects were stronger for vestibular stimuli. All behavioral deficits recovered within 36 h. Visual deficits were larger following inactivation of the posterior portion of the PIVC, likely because these injections encroached upon the VPS area, which contains neurons with optic flow tuning (unlike the PIVC). In contrast, VIP inactivation led to no behavioral deficits, despite the fact that VIP neurons show much stronger choice-related activity than MSTd neurons. These results suggest that the VIP area either provides a parallel and partially redundant pathway for this task, or does not participate in heading discrimination. In contrast, the PIVC/VPS area, along with the MSTd area, make causal contributions to heading perception based on either vestibular or visual signals. SIGNIFICANCE STATEMENT: Multisensory vestibular and visual signals are found in multiple cortical areas, but their causal contribution to self-motion perception has been previously tested only in the dorsal medial superior temporal (MSTd) area. In these experiments, we show that inactivation of the parietoinsular vestibular cortex (PIVC) also results in causal deficits during heading discrimination for both visual and vestibular cues. In contrast, ventral intraparietal (VIP) area inactivation led to no behavioral deficits, despite the fact that VIP neurons show much stronger choice-related activity than MSTd or PIVC neurons. These results demonstrate that choice-related activity does not always imply a causal role in sensory perception.
Assuntos
Movimentos da Cabeça/fisiologia , Percepção de Movimento/fisiologia , Fluxo Óptico/fisiologia , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Animais , Mapeamento Encefálico , Sinais (Psicologia) , Discriminação Psicológica , Lateralidade Funcional/efeitos dos fármacos , Agonistas de Receptores de GABA-A/farmacologia , Movimentos da Cabeça/efeitos dos fármacos , Processamento de Imagem Assistida por Computador , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Percepção de Movimento/efeitos dos fármacos , Muscimol/farmacologia , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Lobo Parietal/efeitos dos fármacos , Estimulação Luminosa , Psicometria , Psicofísica , Lobo Temporal/efeitos dos fármacosRESUMO
The starburst amacrine cell in the mouse retina presents an opportunity to examine the precise role of sensory input location on neuronal computations. Using visual receptive field mapping, glutamate uncaging, two-photon Ca(2+) imaging, and genetic labeling of putative synapses, we identify a unique arrangement of excitatory inputs and neurotransmitter release sites on starburst amacrine cell dendrites: the excitatory input distribution is skewed away from the release sites. By comparing computational simulations with Ca(2+) transients recorded near release sites, we show that this anatomical arrangement of inputs and outputs supports a dendritic mechanism for computing motion direction. Direction-selective Ca(2+) transients persist in the presence of a GABA-A receptor antagonist, though the directional tuning is reduced. These results indicate a synergistic interaction between dendritic and circuit mechanisms for generating direction selectivity in the starburst amacrine cell.
Assuntos
Células Amácrinas/fisiologia , Dendritos/fisiologia , Modelos Neurológicos , Percepção de Movimento/fisiologia , Orientação/fisiologia , Retina/citologia , Sinapses/fisiologia , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Células Amácrinas/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Simulação por Computador , Proteína 4 Homóloga a Disks-Large , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Ácido Glutâmico/farmacologia , Guanilato Quinases/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Percepção de Movimento/efeitos dos fármacos , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/ultraestrutura , Vias Visuais/fisiologiaRESUMO
Recent studies have shown that the neuropeptide oxytocin is involved in the regulation of several complex human social behaviours. There is, however, little research on the effect of oxytocin on basic mechanisms underlying human sociality, such as the perception of biological motion. In the present study, we investigated the effect of oxytocin on biological motion perception in dogs (Canis familiaris), a species adapted to the human social environment and thus widely used to model many aspects of human social behaviour. In a within-subjects design, dogs (N = 39), after having received either oxytocin or placebo treatment, were presented with 2D projection of a moving point-light human figure and the inverted and scrambled version of the same movie. Heart rate (HR) and heart rate variability (HRV) were measured as physiological responses, and behavioural response was evaluated by observing dogs' looking time. Subjects were also rated on the personality traits of Neuroticism and Agreeableness by their owners. As expected, placebo-pretreated (control) dogs showed a spontaneous preference for the biological motion pattern; however, there was no such preference after oxytocin pretreatment. Furthermore, following the oxytocin pretreatment female subjects looked more at the moving point-light figure than males. The individual variations along the dimensions of Agreeableness and Neuroticism also modulated dogs' behaviour. Furthermore, HR and HRV measures were affected by oxytocin treatment and in turn played a role in subjects' looking behaviour. We discuss how these findings contribute to our understanding of the neurohormonal regulatory mechanisms of human (and non-human) social skills.
Assuntos
Comportamento Animal/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Percepção de Movimento/efeitos dos fármacos , Ocitocina/farmacologia , Animais , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Personalidade , Comportamento SocialRESUMO
Although craving states are important to both cocaine dependence (CD) and pathological gambling (PG), few studies have directly investigated neurobiological similarities and differences in craving between these disorders. We used functional magnetic resonance imaging (fMRI) to assess brain activity in 103 participants (30 CD, 28 PG, and 45 controls) while they watched videos depicting cocaine, gambling, and sad scenarios to investigate the neural correlates of craving. We observed a three-way urge type × video type × diagnostic group interaction in self-reported craving, with CD participants reporting strong cocaine cravings to cocaine videos, and PG participants reporting strong gambling urges to gambling videos. Neuroimaging data revealed a diagnostic group × video interaction in anterior cingulate cortex/ventromedial prefrontal cortex (mPFC), activating predominantly to cocaine videos in CD participants, and a more dorsal mPFC region that was most strongly activated for cocaine videos in CD participants, gambling videos in PG participants, and sad videos in control participants. Gender × diagnosis × video interactions identified dorsal mPFC and a region in posterior insula/caudate in which female but not male PG participants showed increased responses to gambling videos. Findings illustrate both similarities and differences in the neural correlates of drug cravings and gambling urges in CD and PG. Future studies should investigate diagnostic- and gender-specific therapies targeting the neural systems implicated in craving/urge states in addictions.
Assuntos
Encéfalo/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Fissura/fisiologia , Jogo de Azar/fisiopatologia , Adolescente , Adulto , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Cocaína/administração & dosagem , Fissura/efeitos dos fármacos , Inibidores da Captação de Dopamina/administração & dosagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Testes Neuropsicológicos , Adulto JovemRESUMO
Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Aprendizagem/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Recompensa , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Mapeamento Encefálico , Bupropiona/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Literatura Erótica , Lateralidade Funcional , Humanos , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética , Masculino , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Testes Neuropsicológicos , Núcleo Accumbens/fisiologia , Paroxetina/farmacologia , Comportamento Sexual/efeitos dos fármacos , Comportamento Sexual/fisiologiaRESUMO
Action observation is known to trigger predictions of the ongoing course of action and thus considered a hallmark example for predictive perception. A related task, which explicitly taps into the ability to predict actions based on their internal representations, is action segmentation; the task requires participants to demarcate where one action step is completed and another one begins. It thus benefits from a temporally precise prediction of the current action. Formation and exploitation of these temporal predictions of external events is now closely associated with a network including the basal ganglia and prefrontal cortex. Because decline of dopaminergic innervation leads to impaired function of the basal ganglia and prefrontal cortex in Parkinson's disease (PD), we hypothesised that PD patients would show increased temporal variability in the action segmentation task, especially under medication withdrawal (hypothesis 1). Another crucial aspect of action segmentation is its reliance on a semantic representation of actions. There is no evidence to suggest that action representations are substantially altered, or cannot be accessed, in non-demented PD patients. We therefore expected action segmentation judgments to follow the same overall patterns in PD patients and healthy controls (hypothesis 2), resulting in comparable segmentation profiles. Both hypotheses were tested with a novel classification approach. We present evidence for both hypotheses in the present study: classifier performance was slightly decreased when it was tested for its ability to predict the identity of movies segmented by PD patients, and a measure of normativity of response behaviour was decreased when patients segmented movies under medication-withdrawal without access to an episodic memory of the sequence. This pattern of results is consistent with hypothesis 1. However, the classifier analysis also revealed that responses given by patients and controls create very similar action-specific patterns, thus delivering evidence in favour hypothesis 2. In terms of methodology, the use of classifiers in the present study allowed us to establish similarity of behaviour across groups (hypothesis 2). The approach opens up a new avenue that standard statistical methods often fail to provide and is discussed in terms of its merits to measure hypothesised similarities across study populations.
Assuntos
Memória , Modelos Psicológicos , Percepção de Movimento , Doença de Parkinson/psicologia , Adulto , Idoso , Antiparkinsonianos/uso terapêutico , Gânglios da Base/fisiopatologia , Simulação por Computador , Agonistas de Dopamina/uso terapêutico , Humanos , Julgamento/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Pessoa de Meia-Idade , Modelos Neurológicos , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Destreza Motora/efeitos dos fármacos , Destreza Motora/fisiologia , Testes Neuropsicológicos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Estimulação Luminosa , SemânticaRESUMO
The formation of selective sensitivity to the movement of the environment at different velocities still remains an unsolved problem. It is assumed that the basis of the creation of such sensitivity can be as processes of inhibition and facilitation at different levels of the visual system. We studied the role of GABA-ergic inhibition in shaping the velocity tuning by affecting GABA antagonist iontophoresis, bicuculine on responses that occur in 80 neurons of the superior colliculus (SC) on the movement of the light spot at 5-45 degrees/s in hamsters anesthetized by urethane. After the bicuculine iontophoresis compared with the controls 30% of units have changed the velocity tuning category; 61.25% of neurons modified their velocity selectivity more than 10%; 8.75% of cells were found without similar changes. These data suggest that the intracollicular GABA-ergic chains are involved in the formation of velocity tuning of SC-neurons.