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1.
J Neurophysiol ; 125(6): 2068-2083, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33826443

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 fármacos
2.
J Neurophysiol ; 122(2): 691-706, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268830

RESUMO

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/farmacologia
3.
Int J Neuropsychopharmacol ; 21(7): 649-655, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29618012

RESUMO

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 Jovem
4.
J Neurosci ; 36(36): 9303-12, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27605607

RESUMO

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 Jovem
5.
J Neurosci ; 36(13): 3789-98, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-27030763

RESUMO

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 fármacos
6.
Nature ; 469(7330): 402-6, 2011 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-21131947

RESUMO

Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells (SACs) onto four subtypes of ON-OFF direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions. It has been reported in rabbit that the SACs on the 'null' sides of DSGCs form functional GABA (γ-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not. However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity.


Assuntos
Modelos Neurológicos , Inibição Neural/fisiologia , Retina/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Células Amácrinas/efeitos dos fármacos , Células Amácrinas/fisiologia , Animais , Dendritos/fisiologia , Condutividade Elétrica , Camundongos , Camundongos Transgênicos , Movimento (Física) , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Muscimol/farmacologia , Inibição Neural/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Estimulação Luminosa , Piridazinas/farmacologia , Retina/citologia , Retina/efeitos dos fármacos , Retina/crescimento & desenvolvimento , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo
7.
Neuroimage ; 141: 52-59, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27402599

RESUMO

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 Jovem
8.
Anim Cogn ; 19(3): 513-22, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26742930

RESUMO

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 Social
9.
J Neurosci ; 34(6): 2254-63, 2014 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-24501364

RESUMO

Visual systems extract directional motion information from spatiotemporal luminance changes on the retina. An algorithmic model, the Reichardt detector, accounts for this by multiplying adjacent inputs after asymmetric temporal filtering. The outputs of two mirror-symmetrical units tuned to opposite directions are thought to be subtracted on the dendrites of wide-field motion-sensitive lobula plate tangential cells by antagonistic transmitter systems. In Drosophila, small-field T4/T5 cells carry visual motion information to the tangential cells that are depolarized during preferred and hyperpolarized during null direction motion. While preferred direction input is likely provided by excitation from T4/T5 terminals, the origin of null direction inhibition is unclear. Probing the connectivity between T4/T5 and tangential cells in Drosophila using a combination of optogenetics, electrophysiology, and pharmacology, we found a direct excitatory as well as an indirect inhibitory component. This suggests that the null direction response is caused by feedforward inhibition via yet unidentified neurons.


Assuntos
Percepção de Movimento/fisiologia , Inibição Neural/fisiologia , Optogenética/métodos , Estimulação Luminosa/métodos , Visão Ocular/fisiologia , Animais , Drosophila , Feminino , Mecamilamina/farmacologia , Percepção de Movimento/efeitos dos fármacos , Inibição Neural/efeitos dos fármacos , Picrotoxina/farmacologia , Visão Ocular/efeitos dos fármacos , Vias Visuais/efeitos dos fármacos , Vias Visuais/fisiologia
10.
Alcohol Clin Exp Res ; 39(4): 640-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25833025

RESUMO

BACKGROUND: Psychophysical and behavioral studies have demonstrated that perception of motion can be impaired by acute alcohol exposure. The neural activities of posteromedial lateral suprasylvian cortex (PMLS) of cats are directly linked to the perception of visual motion speed. To date, there have been no studies on the effects of acute alcohol exposure in vivo upon the representation of speed in PMLS neurons. METHODS: Alcohol was administered intravenously as a 20% (v/v) saline solution via a syringe at a dose levels of 0.5, 1, or 2 g/kg to generate a series of blood alcohol concentrations. Using extracellular single-unit recording technique, we recorded the speed-tuning properties of PMLS neurons that responded to random-dot patterns before and after alcohol administration, and simultaneously monitored the concentration of ethanol by detecting the breath alcohol concentration using a breath analyzer. RESULTS: After acute alcohol treatment, PMLS cells preferred lower speeds. A broadened speed-tuning bandwidth of PMLS cells was also observed after acute alcohol administration. Additionally, response modulation and discriminative capacity for speed of visual motion in the PMLS cells were significantly impaired after acute alcohol exposure. Concurrently, PMLS cells after acute alcohol exposure showed decreased spontaneous activity, peak responses, and signal-to-noise ratios. CONCLUSIONS: There is a significant functional degradation in the neural representation of visual motion speed in PMLS of cats after acute alcohol exposure. These neural changes may contribute to the alcohol-related deficits in visual motion perception observed in behavioral studies.


Assuntos
Etanol/administração & dosagem , Etanol/farmacologia , Percepção de Movimento/efeitos dos fármacos , Córtex Visual/efeitos dos fármacos , Animais , Gatos , Relação Dose-Resposta a Droga , Percepção de Movimento/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Estimulação Luminosa , Córtex Visual/citologia , Córtex Visual/fisiologia
11.
Behav Pharmacol ; 26(4): 407-10, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25738760

RESUMO

Evidence of observational learning (social learning) is present in many species. One such task is the one-trial taste-avoidance task, in which Actor chicks peck a bead coated with an aversant substance. Observer chicks learn to avoid beads that are similar in appearance to the one presented to the Actors. It has been firmly established that active learning of the one-trial taste-avoidance task is dependent on a constrained level of glutamate receptor activation. The current study examined the effects of memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, on the learning by Observers. Memantine produced an inverted U-shaped dose-dependent response curve; 1.0 mmol/l memantine produced significant improvement. These results demonstrate that memantine influences memory formation for observational learning in the day-old chick and support the hypothesis that memantine can improve memories by altering levels of glutamate during memory formation.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Memantina/farmacologia , Nootrópicos/farmacologia , Aprendizado Social/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/fisiologia , Galinhas , Discriminação Psicológica/efeitos dos fármacos , Discriminação Psicológica/fisiologia , Relação Dose-Resposta a Droga , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologia , Masculino , Modelos Animais , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Testes Neuropsicológicos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Aprendizado Social/fisiologia
12.
Int J Neuropsychopharmacol ; 18(2)2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25612894

RESUMO

BACKGROUND: Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. METHODS: Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. RESULTS: Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. CONCLUSIONS: In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Encéfalo/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Literatura Erótica , Morfolinas/farmacologia , Sulpirida/análogos & derivados , Adulto , Amissulprida , Encéfalo/fisiologia , Mapeamento Encefálico , Estudos Cross-Over , Método Duplo-Cego , Humanos , Imageamento por Ressonância Magnética , Masculino , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Estimulação Luminosa , Reboxetina , Comportamento Sexual/efeitos dos fármacos , Comportamento Sexual/fisiologia , Sulpirida/farmacologia , Inquéritos e Questionários , Gravação em Vídeo , Adulto Jovem
13.
Cerebellum ; 12(1): 97-107, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22777507

RESUMO

Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and perception; second, there are nonoverlapping neural networks: one might be involved in perception and the other for the VOR. We investigated these possibilities by measuring VOR and perceptual responses in healthy human subjects during whole-body, constant-velocity rotation steps about all three dimensions (yaw, pitch, and roll) before and after 10 mg of 4-aminopyridine (4-AP). 4-AP, a selective blocker of inward rectifier potassium conductance, can lead to increased synchronization and precision of Purkinje neuron discharge and possibly enhance the GABAergic action. Hence 4-AP could reduce the decay time constant of the perceived angular velocity and VOR. We found that 4-AP reduced the decay time constant, but the amount of reduction in the two processes, perception and VOR, was not the same, suggesting the possibility of nonoverlapping or partially overlapping neural substrates for VOR and perception. We also noted that, unlike the VOR, the perceived angular velocity gradually built up and plateau prior to decay. Hence, the perception pathway may have additional mechanism that changes the dynamics of perceived angular velocity beyond the velocity storage. 4-AP had no effects on the duration of build-up of perceived angular velocity, suggesting that the higher order processing of perception, beyond the velocity storage, might not occur under the influence of mechanism that could be influenced by 4-AP.


Assuntos
4-Aminopiridina/administração & dosagem , Cerebelo/fisiologia , Movimentos Oculares/fisiologia , Percepção de Movimento/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Adulto , Tronco Encefálico/fisiologia , Cerebelo/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/administração & dosagem , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/fisiologia , Reflexo Vestíbulo-Ocular/efeitos dos fármacos , Rotação , Vestíbulo do Labirinto/efeitos dos fármacos , Vestíbulo do Labirinto/fisiologia
14.
Eur J Neurosci ; 36(8): 3030-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22775326

RESUMO

Locomotor activity like walking or flying has recently been shown to alter visual processing in several species. In insects, the neuromodulator octopamine is thought to play an important role in mediating state changes during locomotion of the animal [K.D. Longden & H.G. Krapp (2009) J. Neurophysiol., 102, 3606-3618; (2010) Front. Syst. Neurosci., 4, 153; S.N. Jung et al. (2011)J. Neurosci., 31, 9231-9237]. Here, we used the octopamine agonist chlordimeform (CDM) to mimic effects of behavioural state changes on visual motion processing. We recorded from identified motion-sensitive visual interneurons in the lobula plate of the blowfly Calliphora vicina. In these neurons, which are thought to be involved in visual guidance of locomotion, motion adaptation leads to a prominent attenuation of contrast sensitivity. Following CDM application, the neurons maintained high contrast sensitivity in the adapted state. This modulation of contrast gain adaptation was independent of the activity of the recorded neurons, because it was also present after stimulation with visual motion that did not result in deviations from the neurons' resting activity. We conclude that CDM affects presynaptic inputs of the recorded neurons. Accordingly, the effect of CDM was weak when adapting and test stimuli were presented in different parts of the receptive field, stimulating separate populations of local presynaptic neurons. In the peripheral visual system adaptation depends on the temporal frequency of the stimulus pattern and is therefore related to pattern velocity. Contrast gain adaptation could therefore be the basis for a shift in the velocity tuning that was previously suggested to contribute to state-dependent processing of visual motion information in the lobula plate interneurons.


Assuntos
Sensibilidades de Contraste/efeitos dos fármacos , Interneurônios/fisiologia , Octopamina/agonistas , Adaptação Fisiológica , Animais , Encéfalo/fisiologia , Clorfenamidina/farmacologia , Sensibilidades de Contraste/fisiologia , Dípteros , Feminino , Interneurônios/metabolismo , Percepção de Movimento/efeitos dos fármacos , Percepção de Movimento/fisiologia , Octopamina/metabolismo , Fluxo Óptico/fisiologia , Potenciais Sinápticos , Campos Visuais/fisiologia
15.
Nat Neurosci ; 9(5): 682-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16604069

RESUMO

A central goal of cognitive neuroscience is to elucidate the neural mechanisms underlying decision-making. Recent physiological studies suggest that neurons in association areas may be involved in this process. To test this, we measured the effects of electrical microstimulation in the lateral intraparietal area (LIP) while monkeys performed a reaction-time motion discrimination task with a saccadic response. In each experiment, we identified a cluster of LIP cells with overlapping response fields (RFs) and sustained activity during memory-guided saccades. Microstimulation of this cluster caused an increase in the proportion of choices toward the RF of the stimulated neurons. Choices toward the stimulated RF were faster with microstimulation, while choices in the opposite direction were slower. Microstimulation never directly evoked saccades, nor did it change reaction times in a simple saccade task. These results demonstrate that the discharge of LIP neurons is causally related to decision formation in the discrimination task.


Assuntos
Tomada de Decisões/fisiologia , Discriminação Psicológica/fisiologia , Percepção de Movimento/fisiologia , Neurônios/fisiologia , Lobo Parietal/citologia , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Animais , Comportamento Animal , Tomada de Decisões/efeitos da radiação , Discriminação Psicológica/efeitos da radiação , Estimulação Elétrica/métodos , Macaca mulatta , Percepção de Movimento/efeitos dos fármacos , Neurônios/efeitos da radiação , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Tempo de Reação/efeitos da radiação , Movimentos Sacádicos/fisiologia
16.
J Neurophysiol ; 102(6): 3606-18, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19812292

RESUMO

Active locomotive states are metabolically expensive and require efficient sensory processing both to avoid wasteful movements and to cope with an extended bandwidth of sensory stimuli. This is particularly true for flying animals because flight, as opposed to walking or resting, imposes a steplike increase in metabolism for the precise execution and control of movements. Sensory processing itself carries a significant metabolic cost, but the principles governing the adjustment of sensory processing to different locomotor states are not well understood. We use the blowfly as a model system to study the impact on visual processing of a neuromodulator, octopamine, which is known to be involved in the regulation of flight physiology. We applied an octopamine agonist and recorded the directional motion responses of identified visual interneurons known to process self-motion-induced optic flow to directional motion stimuli. The neural response range of these neurons is increased and the response latency is reduced. We also found that, due to an elevated spontaneous spike rate, the cells' negative signaling range is increased. Meanwhile, the preferred self-motion parameters the cells encode were state independent. Our results indicate that in the blowfly energetically expensive sensory coding strategies, such as rapid, large responses, and high spontaneous spike activity could be adjusted by the neuromodulator octopamine, likely to save energy during quiet locomotor states.


Assuntos
Potenciais de Ação/fisiologia , Dípteros/fisiologia , Interneurônios/fisiologia , Percepção de Movimento/fisiologia , Vias Visuais/citologia , Potenciais de Ação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Feminino , Interneurônios/efeitos dos fármacos , Modelos Neurológicos , Percepção de Movimento/efeitos dos fármacos , Octopamina/farmacologia , Estimulação Luminosa/métodos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Campos Visuais/efeitos dos fármacos , Campos Visuais/fisiologia
17.
J Neural Transm Suppl ; (73): 161-71, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20411776

RESUMO

It has been proposed that the basal ganglia are important to the temporal processing of milliseconds- and seconds-range intervals, both within the motor and perceptual domains. This review summarizes and discuses evidence from animal, pharmacological, clinical, and imaging research that supports this proposal, with particular reference to the role of the substantia nigra (SN).


Assuntos
Gânglios da Base/fisiologia , Dopamina/metabolismo , Percepção de Movimento/fisiologia , Substância Negra/fisiologia , Percepção do Tempo/fisiologia , Animais , Atenção/fisiologia , Dopaminérgicos/farmacologia , Humanos , Imageamento por Ressonância Magnética/métodos , Modelos Biológicos , Percepção de Movimento/efeitos dos fármacos , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , Tempo de Reação/fisiologia , Percepção do Tempo/efeitos dos fármacos
18.
Neurotoxicology ; 72: 107-113, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30790592

RESUMO

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/metabolismo
19.
J Neurosci ; 27(3): 529-41, 2007 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-17234585

RESUMO

Past work has suggested that the medial superior temporal area (MST) is involved in the initiation of three kinds of eye movements at short latency by large-field visual stimuli. These eye movements consist of (1) version elicited by linear motion (the ocular following response), (2) vergence elicited by binocular parallax (the disparity vergence response), and (3) vergence elicited by global motion toward or away from the fovea (the radial-flow vergence response). We investigated this hypothesis by recording the effects of ibotenic acid injections in the superior temporal sulcus (STS) of both hemispheres in five monkeys. After the injections, all three kinds of eye movements were significantly impaired, with the magnitude of the impairments often showing a strong correlation with the extent of the morphological damage in the three subregions of the STS: dorsal MST on the anterior bank, lateral MST and middle temporal area on the posterior bank. However, the extent of the lesions in the three subregions often covaried, rendering it difficult to assess their relative contributions to the various deficits. The effects of the lesions on other aspects of oculomotor behavior that are known to be important for the normal functioning of the three tracking mechanisms (e.g., ocular stability, fixation disparity) were judged to be generally minor and to contribute little to the impairments. We conclude that, insofar as MST sustained significant damage in all injected hemispheres, our findings are consistent with the hypothesis that MST is a primary site for initiating all three visual tracking eye movements at ultra-short latencies.


Assuntos
Movimentos Oculares/fisiologia , Ácido Ibotênico/toxicidade , Percepção de Movimento/fisiologia , Tempo de Reação/fisiologia , Lobo Temporal/fisiologia , Animais , Movimentos Oculares/efeitos dos fármacos , Macaca , Percepção de Movimento/efeitos dos fármacos , Estimulação Luminosa/métodos , Tempo de Reação/efeitos dos fármacos , Lobo Temporal/efeitos dos fármacos , Córtex Visual/efeitos dos fármacos , Córtex Visual/fisiologia , Campos Visuais/efeitos dos fármacos , Campos Visuais/fisiologia , Vias Visuais/efeitos dos fármacos , Vias Visuais/fisiologia
20.
Clin Neurophysiol ; 119(7): 1486-95, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18450506

RESUMO

OBJECTIVE: With MEG and EEG the effect of perinatal dioxin load of 38 healthy 7- to 12-year-old children was studied to assess possible disturbances of visual development. METHODS: Latencies and amplitudes of the motion (N2 with subcomponents) and oddball responses (N200 and P3b) were analysed after age correction. RESULTS: With increasing load, latencies increased and the amplitudes of the oddball components tended to be reduced. The latency increase between the high- and low-loaded children was about 13 ms (P<0.004) and the oddball response showed an amplitude decrease of 12% (P=0.009). CONCLUSIONS: It may be concluded that, during the end-80s/early-90s, exposure to background levels in industrialized regions seems to have resulted in small underdevelopment or damage to visual motion processing and visual cognition. SIGNIFICANCE: Since dioxin pollution by incinerators still exists in many regions in developing countries and also still, although at a smaller scale, in the industrialized world, perinatal loads of similar magnitude and possibly more as measured in this study may occur and as a consequence might affect the developing brain.


Assuntos
Deficiências do Desenvolvimento/induzido quimicamente , Deficiências do Desenvolvimento/prevenção & controle , Dioxinas/toxicidade , Eletroencefalografia/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Magnetoencefalografia/efeitos dos fármacos , Percepção de Movimento/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Percepção Visual/efeitos dos fármacos , Tecido Adiposo/química , Envelhecimento/psicologia , Criança , Depressão Química , Dioxinas/análise , Relação Dose-Resposta a Droga , Poluentes Ambientais/análise , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Países Baixos , Estimulação Luminosa , Gravidez , Valores de Referência , Visão Binocular/efeitos dos fármacos
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