RESUMEN
Paired-pulse transcranial magnetic stimulation is a valuable tool for investigating inhibitory mechanisms in motor cortex. We recently demonstrated its use in measuring cortical inhibition in visual cortex, using an approach in which participants trace the size of phosphenes elicited by stimulation to occipital cortex. Here, we investigate age-related differences in primary visual cortical inhibition and the relationship between primary visual cortical inhibition and local GABA+ in the same region, estimated using magnetic resonance spectroscopy. GABA+ was estimated in 28 young (18 to 28 years) and 47 older adults (65 to 84 years); a subset (19 young, 18 older) also completed a paired-pulse transcranial magnetic stimulation session, which assessed visual cortical inhibition. The paired-pulse transcranial magnetic stimulation measure of inhibition was significantly lower in older adults. Uncorrected GABA+ in primary visual cortex was also significantly lower in older adults, while measures of GABA+ that were corrected for the tissue composition of the magnetic resonance spectroscopy voxel were unchanged with age. Furthermore, paired-pulse transcranial magnetic stimulation-measured inhibition and magnetic resonance spectroscopy-measured tissue-corrected GABA+ were significantly positively correlated. These findings are consistent with an age-related decline in cortical inhibition in visual cortex and suggest paired-pulse transcranial magnetic stimulation effects in visual cortex are driven by GABAergic mechanisms, as has been demonstrated in motor cortex.
Asunto(s)
Envejecimiento , Espectroscopía de Resonancia Magnética , Inhibición Neural , Estimulación Magnética Transcraneal , Corteza Visual , Ácido gamma-Aminobutírico , Humanos , Estimulación Magnética Transcraneal/métodos , Adulto , Anciano , Masculino , Femenino , Adulto Joven , Espectroscopía de Resonancia Magnética/métodos , Inhibición Neural/fisiología , Ácido gamma-Aminobutírico/metabolismo , Anciano de 80 o más Años , Adolescente , Envejecimiento/fisiología , Corteza Visual/fisiología , Corteza Visual/diagnóstico por imagenRESUMEN
Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection neurons, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition.
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Interneuronas , Bulbo Olfatorio , Animales , Interneuronas/fisiología , Interneuronas/metabolismo , Bulbo Olfatorio/fisiología , Bulbo Olfatorio/citología , Bulbo Olfatorio/metabolismo , Ratones , Potenciales de Acción/fisiología , Inhibición Neural/fisiología , Ratones Endogámicos C57BL , Masculino , Sinapsis/fisiología , Sinapsis/metabolismo , Técnicas de Placa-Clamp , Dendritas/fisiología , Dendritas/metabolismo , Parvalbúminas/metabolismo , FemeninoRESUMEN
The medial prefrontal cortex (mPFC) plays a pivotal role in regulating working memory, executive function, and self-regulatory behaviors. Dysfunction in the mPFC circuits is a characteristic feature of several neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Chronic stress (CS) is widely recognized as a major triggering factor for the onset of these disorders. Although evidence suggests synaptic dysfunction in mPFC circuits following CS exposure, it remains unclear how different neuronal populations in the infralimbic (IL) and prelimbic (PL) cortices are affected in terms of synaptic inhibition/excitation balance (I/E ratio). Here, using neuroproteomic analysis and whole-cell patch-clamp recordings in pyramidal neurons (PNs) and parvalbumin (PV) interneurons within the PL and IL cortices, we examined the synaptic changes after 21â d of chronic unpredictable stress, in male mice. Our results reveal distinct impacts of CS on PL and IL PNs, resulting in an increased I/E ratio in both subregions but through different mechanisms: CS increases inhibitory synaptic drive in the PL while decreasing excitatory synaptic drive in the IL. Notably, the I/E ratio and excitatory and inhibitory synaptic drive of PV interneurons remained unaffected in both PL and IL circuits following CS exposure. These findings offer novel mechanistic insights into the influence of CS on mPFC circuits and support the hypothesis of stress-induced mPFC hypofunction.
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Interneuronas , Ratones Endogámicos C57BL , Parvalbúminas , Corteza Prefrontal , Células Piramidales , Estrés Psicológico , Animales , Interneuronas/fisiología , Interneuronas/metabolismo , Células Piramidales/fisiología , Masculino , Estrés Psicológico/fisiopatología , Parvalbúminas/metabolismo , Inhibición Neural/fisiología , Ratones , Técnicas de Placa-Clamp , Potenciales Postsinápticos Excitadores/fisiología , Sinapsis/fisiología , Potenciales Postsinápticos Inhibidores/fisiologíaRESUMEN
Cerebellar brain inhibition (CBI) is an inhibitory output from the cerebellum to the primary motor cortex, which is decreased in early motor learning. Transcranial random noise stimulation (tRNS) is a noninvasive brain stimulation to induce brain plastic changes; however, the effects of cerebellar tRNS on CBI and motor learning have not been investigated yet to our knowledge. In this study, whether cerebellar tRNS decreases CBI and improves motor learning was examined, and pupil diameter was measured to examine physiological changes due to the effect of tRNS on motor learning. Thirty-four healthy subjects were assigned to either the cerebellar tRNS group or the Sham group. The subjects performed visuomotor tracking task with ten trials each in the early and late learning stages while receiving the stimulus intervention. CBI and motor evoked potentials were measured before the learning task, after the early learning stage, and after the late learning stage, and pupil diameter was measured during the task. There was no change in CBI in both groups. No group differences in motor learning rates were observed at any learning stages. Pupil diameter was smaller in the late learning stage than in the early learning stage in both groups. The cerebellar tRNS was suggested not to induce changes in CBI and improvement in motor learning, and it did not affect pupil diameter.
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Cerebelo , Potenciales Evocados Motores , Aprendizaje , Desempeño Psicomotor , Pupila , Estimulación Transcraneal de Corriente Directa , Humanos , Masculino , Femenino , Pupila/fisiología , Cerebelo/fisiología , Aprendizaje/fisiología , Adulto Joven , Adulto , Potenciales Evocados Motores/fisiología , Desempeño Psicomotor/fisiología , Inhibición Neural/fisiología , Corteza Motora/fisiologíaRESUMEN
BACKGROUND: Ovarian hormones influence the propensity for short-term plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Estradiol appears to enhance the propensity for neural plasticity. It is currently unknown how progesterone influences short-term plasticity induced by rTMS. OBJECTIVE: The present research investigates whether the luteal versus follicular phase of the menstrual cycle influence short-term plasticity induced by intermittent theta-burst stimulation (iTBS). We tested the hypothesis that iTBS would increase motor evoked potentials (MEPs) during the follicular phase. Further, we explored the effects of the luteal phase on iTBS-induced neural plasticity. METHOD: Twenty-nine adult females participated in a placebo-controlled study that delivered real and sham iTBS to the left primary motor cortex in separate sessions corresponding to the follicular phase (real iTBS), luteal phase (real iTBS), and a randomly selected day (sham iTBS). Outcomes included corticospinal excitability as measured by the amplitude of MEPs and short-interval intracortical inhibition (SICI) recorded from the right first dorsal interosseous muscle before and following iTBS (612 pulses). RESULTS: MEP amplitude was increased following real iTBS during the follicular condition. No significant changes in MEP amplitude were observed during the luteal or sham visits. SICI was unchanged by iTBS irrespective of menstrual phase. CONCLUSION: These findings suggest women experience a variable propensity for iTBS-induced short-term plasticity across the menstrual cycle. This information is important for designing studies aiming to induce plasticity via rTMS in women.
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Potenciales Evocados Motores , Ciclo Menstrual , Corteza Motora , Plasticidad Neuronal , Estimulación Magnética Transcraneal , Humanos , Femenino , Plasticidad Neuronal/fisiología , Potenciales Evocados Motores/fisiología , Adulto , Corteza Motora/fisiología , Adulto Joven , Ciclo Menstrual/fisiología , Electromiografía , Ritmo Teta/fisiología , Inhibición Neural/fisiologíaRESUMEN
The brain functions as a prediction machine, utilizing an internal model of the world to anticipate sensations and the outcomes of our actions. Discrepancies between expected and actual events, referred to as prediction errors, are leveraged to update the internal model and guide our attention towards unexpected events1-10. Despite the importance of prediction-error signals for various neural computations across the brain, surprisingly little is known about the neural circuit mechanisms responsible for their implementation. Here we describe a thalamocortical disinhibitory circuit that is required for generating sensory prediction-error signals in mouse primary visual cortex (V1). We show that violating animals' predictions by an unexpected visual stimulus preferentially boosts responses of the layer 2/3 V1 neurons that are most selective for that stimulus. Prediction errors specifically amplify the unexpected visual input, rather than representing non-specific surprise or difference signals about how the visual input deviates from the animal's predictions. This selective amplification is implemented by a cooperative mechanism requiring thalamic input from the pulvinar and cortical vasoactive-intestinal-peptide-expressing (VIP) inhibitory interneurons. In response to prediction errors, VIP neurons inhibit a specific subpopulation of somatostatin-expressing inhibitory interneurons that gate excitatory pulvinar input to V1, resulting in specific pulvinar-driven response amplification of the most stimulus-selective neurons in V1. Therefore, the brain prioritizes unpredicted sensory information by selectively increasing the salience of unpredicted sensory features through the synergistic interaction of thalamic input and neocortical disinhibitory circuits.
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Interneuronas , Corteza Visual Primaria , Tálamo , Péptido Intestinal Vasoactivo , Animales , Ratones , Masculino , Péptido Intestinal Vasoactivo/metabolismo , Interneuronas/fisiología , Femenino , Tálamo/fisiología , Tálamo/citología , Corteza Visual Primaria/fisiología , Corteza Visual Primaria/citología , Pulvinar/fisiología , Pulvinar/citología , Modelos Neurológicos , Estimulación Luminosa , Inhibición Neural/fisiología , Somatostatina/metabolismo , Ratones Endogámicos C57BL , Corteza Visual/fisiología , Corteza Visual/citología , Vías Visuales/fisiologíaRESUMEN
The triggers of status epilepticus (SE) in non-epileptic patients can vary widely, from idiopathic causes to exposure to chemoconvulsants. Regardless of its etiology, prolonged SE can cause significant brain damage, commonly resulting in the development of epilepsy, which is often accompanied by increased anxiety. GABAA receptor (GABAAR)-mediated inhibition has a central role among the mechanisms underlying brain damage and the ensuing epilepsy and anxiety. During SE, calcium influx primarily via ionotropic glutamate receptors activates signaling cascades which trigger a rapid internalization of synaptic GABAARs; this weakens inhibition, exacerbating seizures and excitotoxicity. GABAergic interneurons are more susceptible to excitotoxic death than principal neurons. During the latent period of epileptogenesis, the aberrant reorganization in synaptic interactions that follow interneuronal loss in injured brain regions, leads to the formation of hyperexcitable, seizurogenic neuronal circuits, along with disturbances in brain oscillatory rhythms. Reduction in the spontaneous, rhythmic "bursts" of IPSCs in basolateral amygdala neurons is likely to play a central role in anxiogenesis. Protecting interneurons during SE is key to preventing both epilepsy and anxiety. Antiglutamatergic treatments, including antagonism of calcium-permeable AMPA receptors, can be expected to control seizures and reduce excitotoxicity not only by directly suppressing hyperexcitation, but also by counteracting the internalization of synaptic GABAARs. Benzodiazepines, as delayed treatment of SE, have low efficacy due to the reduction and dispersion of their targets (the synaptic GABAARs), but also because themselves contribute to further reduction of available GABAARs at the synapse; furthermore, benzodiazepines may be completely ineffective in the immature brain.
Asunto(s)
Ansiedad , Receptores de GABA-A , Estado Epiléptico , Estado Epiléptico/metabolismo , Receptores de GABA-A/metabolismo , Animales , Humanos , Ansiedad/metabolismo , Inhibición Neural/fisiologíaRESUMEN
The maturation of cerebral cortical networks during early life involves a major reorganization of long-range axonal connections. In a recent study, Bragg-Gonzalo, Aguilera, et al. discovered that in mice, the interhemispheric connections sent by S1L4 callosal projection neurons are pruned via the tight control of their ipsilateral synaptic integration, which relies on the early activity of specific interneurons.
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Corteza Cerebral , Inhibición Neural , Animales , Inhibición Neural/fisiología , Corteza Cerebral/fisiología , Humanos , Neuronas/fisiología , Vías Nerviosas/fisiología , Cuerpo Calloso/fisiología , Interneuronas/fisiología , Red Nerviosa/fisiología , RatonesRESUMEN
Adolescent inhibition of thalamocortical projections from postnatal days P20 to 50 leads to long-lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamoprefrontal projections in male/female mice from P20 to P35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (mediodorsal thalamus (MD), nucleus accumbens (NAc), or callosal prefrontal projections) 24â h later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III NAc and layer V/VI MD-projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but not excitatory currents was enhanced in contralateral mPFC-projecting neurons. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition in each cell was only altered in the contralateral mPFC projections. This finding suggests homeostatic regulation occurs within subcortically but not intracortical callosal-projecting neurons. Increased inhibition of intraprefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation. Finally, we observed cognitive deficits in the adult mouse using this narrowed window of thalamocortical inhibition.
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Inhibición Neural , Vías Nerviosas , Corteza Prefrontal , Tálamo , Animales , Corteza Prefrontal/fisiología , Vías Nerviosas/fisiología , Masculino , Femenino , Ratones , Inhibición Neural/fisiología , Tálamo/fisiología , Ratones Endogámicos C57BL , Núcleo Accumbens/fisiología , Células Piramidales/fisiología , Potenciales Postsinápticos Inhibidores/fisiología , Potenciales Postsinápticos Excitadores/fisiologíaRESUMEN
The role of developmental cell death in the formation of brain circuits is not well understood. Cajal-Retzius cells constitute a major transient neuronal population in the mammalian neocortex, which largely disappears at the time of postnatal somatosensory maturation. In this study, we used mouse genetics, anatomical, functional, and behavioral approaches to explore the impact of the early postnatal death of Cajal-Retzius cells in the maturation of the cortical circuit. We find that before their death, Cajal-Retzius cells mainly receive inputs from layer 1 neurons, which can only develop their mature connectivity onto layer 2/3 pyramidal cells after Cajal-Retzius cells disappear. This developmental connectivity progression from layer 1 GABAergic to layer 2/3 pyramidal cells regulates sensory-driven inhibition within, and more so, across cortical columns. Here we show that Cajal-Retzius cell death prevention leads to layer 2/3 hyper-excitability, delayed learning and reduced performance in a multi-whisker-dependent texture discrimination task.
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Muerte Celular , Células Piramidales , Corteza Somatosensorial , Animales , Corteza Somatosensorial/fisiología , Corteza Somatosensorial/citología , Ratones , Células Piramidales/fisiología , Células Piramidales/metabolismo , Neocórtex/citología , Neocórtex/fisiología , Neuronas GABAérgicas/fisiología , Neuronas GABAérgicas/metabolismo , Masculino , Vibrisas/fisiología , Femenino , Ratones Endogámicos C57BL , Inhibición Neural/fisiología , Neuronas/fisiología , Neuronas/metabolismoRESUMEN
The effectiveness of activated Ia afferents to discharge α-motoneurons is decreased during passive muscle lengthening compared with static and shortening muscle conditions. Evidence suggests that these regulations are explained by 1) greater postactivation depression induced by homosynaptic postactivation depression (HPAD) and 2) primary afferent depolarization (PAD). It remains uncertain whether muscle length impacts the muscle lengthening-related aspect of regulation of the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and heteronymous Ia facilitation (HF). We conducted a study involving 15 healthy young individuals. We recorded conditioned or nonconditioned soleus Hoffmann (H) reflex with electromyography (EMG) to estimate the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and HF during passive shortening, static, and lengthening muscle conditions at short, intermediate, and long lengths. Our results show that the decrease of effectiveness of activated Ia afferents to discharge α-motoneurons and increase of postactivation depression during passive muscle lengthening occur at all muscle lengths. For PAD and HF, we found that longer muscle length increases the magnitude of regulation related to muscle lengthening. To conclude, our findings support an inhibitory effect (resulting from increased postactivation depression) of muscle lengthening and longer muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. The increase in postactivation depression associated with muscle lengthening can be attributed to the amplification of Ia afferents discharge.NEW & NOTEWORTHY Original results are that in response to passive muscle lengthening and increased muscle length, inhibition of the effectiveness of activated Ia afferents to discharge α-motoneurons increases, with primary afferent depolarization and homosynaptic postactivation depression mechanisms playing central roles in this regulatory process. Our findings highlight for the first time a cumulative inhibitory effect of muscle lengthening and increased muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons.
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Reflejo H , Músculo Esquelético , Músculo Esquelético/fisiología , Masculino , Humanos , Reflejo H/fisiología , Femenino , Adulto , Adulto Joven , Electromiografía , Neuronas Motoras/fisiología , Neuronas Aferentes/fisiología , Inhibición Neural/fisiologíaRESUMEN
Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability.
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Potenciales Evocados Motores , Corteza Motora , Plasticidad Neuronal , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Masculino , Femenino , Adulto , Potenciales Evocados Motores/fisiología , Plasticidad Neuronal/fisiología , Adulto Joven , Corteza Motora/fisiología , Homeostasis/fisiología , Inhibición Neural/fisiología , Ritmo Teta/fisiologíaRESUMEN
OBJECTIVE: Investigating the optimal interstimulus interval (ISI) and the 24-hour test-retest reliability for intrahemispheric dorsal premotor cortex (PMd) - primary motor cortex (M1) connectivity using dual-site transcranial magnetic stimulation (dsTMS). METHODS: In 21 right-handed adults, left intrahemispheric PMd-M1 connectivity has been investigated with a stacked-coil dsTMS setup (conditioning stimulus: 75% of resting motor threshold; test stimulus: eliciting MEPs of 1-1.5 mV) at ISIs of 3, 5-8, and 10 ms. Additionally, M1-M1 short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were investigated to assess comparability to standard paired-pulse setups. RESULTS: Conditioning PMd led to significant inhibition of M1 output at ISIs of 3 and 5 ms, whereas 10 ms resulted in facilitation (all, p < 0.001), with a fair test-retest reliability for 3 (ICC: 0.47) and 6 ms (ICC: 0.44) ISIs. Replication of SICI (p < 0.001) and ICF (p = 0.017) was successful, with excellent test-retest reliability for SICI (ICC: 0.81). CONCLUSION: This dsTMS setup can probe the inhibitory and facilitatory PMd-M1 connections, as well as reliably replicate SICI and ICF paradigms. SIGNIFICANCE: The stacked-coil dsTMS setup for investigating intrahemispheric PMd-M1 connectivity offers promising possibilities to better understand motor control.
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Potenciales Evocados Motores , Corteza Motora , Estimulación Magnética Transcraneal , Humanos , Corteza Motora/fisiología , Estimulación Magnética Transcraneal/métodos , Estimulación Magnética Transcraneal/normas , Masculino , Femenino , Adulto , Reproducibilidad de los Resultados , Potenciales Evocados Motores/fisiología , Adulto Joven , Inhibición Neural/fisiología , Electromiografía/métodosRESUMEN
Mirror neurons show activity during both the execution (AE) and observation of actions (AO). The Mirror Neuron System (MNS) could be involved during motor imagery (MI) as well. Extensive research suggests that the cerebellum is interconnected with the MNS and may be critically involved in its activities. We gathered evidence on the cerebellum's role in MNS functions, both theoretically and experimentally. Evidence shows that the cerebellum plays a major role during AO and MI and that its lesions impair MNS functions likely because, by modulating the activity of cortical inhibitory interneurons with mirror properties, the cerebellum may contribute to visuomotor matching, which is fundamental for shaping mirror properties. Indeed, the cerebellum may strengthen sensory-motor patterns that minimise the discrepancy between predicted and actual outcome, both during AE and AO. Furthermore, through its connections with the hippocampus, the cerebellum might be involved in internal simulations of motor programs during MI. Finally, as cerebellar neuromodulation might improve its impact on MNS activity, we explored its potential neurophysiological and neurorehabilitation implications.
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Cerebelo , Neuronas Espejo , Neuronas Espejo/fisiología , Humanos , Cerebelo/fisiología , Animales , Imaginación/fisiología , Inhibición Neural/fisiología , Actividad Motora/fisiologíaRESUMEN
Evidence continues to accumulate that acute aerobic exercise (AAE) impacts neurophysiological excitability as measured by transcranial magnetic stimulation (TMS). Yet, uncertainty exists about which TMS measures are modulated after AAE in young adults. The influence of AAE intensity and duration of effects are also uncertain. This pre-registered meta-analysis (CRD42017065673) addressed these uncertainties by synthesizing data from 23 studies (including 474 participants) published until February 2024. Meta-analysis was run using a random-effects model and Hedge's g used as effect size. Our results demonstrated a decrease in short-interval intracortical inhibition (SICI) following AAE (g = 0.27; 95â¯% CI [0.16-0.38]; p <.0001), particularly for moderate (g = 0.18; 95â¯% CI [0.05-0.31]; p <.01) and high (g = 0.49; 95â¯% CI [0.27-0.71]; p <.0001) AAE intensities. These effects remained for 30â¯minutes after AAE. Additionally, increased corticospinal excitability was only observed for high intensity AAE (g = 0.28; 95â¯% CI, [0.07-0.48]; p <.01). Our results suggest potential mechanisms for inducing a more susceptible neuroplastic environment following AAE.
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Potenciales Evocados Motores , Ejercicio Físico , Estimulación Magnética Transcraneal , Humanos , Ejercicio Físico/fisiología , Adulto Joven , Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Adulto , Inhibición Neural/fisiologíaRESUMEN
Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress and coupled blood pressure responses. The aim of this study was to investigate whether premenopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27 ± 8 yr) during sudden sensory stimuli (electrical stimuli to a finger) and 3 min of mental stress (forced arithmetics). After sensory stimuli, 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34-100%). The remaining 16 showed no inhibition (mean 5%, range -31 to 28%; one subject exhibiting excitation). During 3 min of mental stress, the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r = 0.64, P = 0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, premenopausal females show a similar range of individual differences in defense-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated.NEW & NOTEWORTHY Muscle sympathetic neural responses to sudden sensory stimuli in premenopausal women showed interindividual differences and the distribution of sympathetic responses was similar to that previously found in men. Despite this similarity, the associated differences in transient blood pressure responses seen in men were not found in women. The increased risk of developing hypertension in postmenopausal women warrants an investigation of whether these response patterns are altered after menopause.
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Presión Sanguínea , Músculo Esquelético , Nervio Peroneo , Premenopausia , Estrés Psicológico , Sistema Nervioso Simpático , Humanos , Femenino , Adulto , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/fisiopatología , Premenopausia/fisiología , Estrés Psicológico/fisiopatología , Presión Sanguínea/fisiología , Nervio Peroneo/fisiología , Músculo Esquelético/fisiología , Adulto Joven , Estimulación Eléctrica/métodos , Inhibición Neural/fisiologíaRESUMEN
OBJECTIVE: This study aimed at investigating the effect of median nerve stimulation on ipsilateral cortical potentials evoked by contralateral median nerve electrical stimulation. METHODS: We recorded somatosensory-evoked potentials (SEPs) from the left parietal cortex in 15 right-handed, healthy subjects. We administered bilateral median nerve stimulation, with the ipsilateral stimulation preceding the stimulation on the contralateral by intervals of 5, 10, 20, or 40 ms. We adjusted these intervals based on each individual's N20 latency. As a measure of S1 excitability, the amplitude of the N20 and the area of the High Frequency Oscillation (HFO) burst were analyzed for each condition. RESULTS: The results revealed significant inhibition of N20 amplitude by ipsilateral median nerve stimulation at interstimulus intervals (ISIs) between 5 and 40 ms. Late HFO burst was suppressed at short ISIs of 5 and 10 ms, pointing to a transcallosal inhibitory effect on S1 intracortical circuits. CONCLUSIONS: Findings suggest interhemispheric interaction between the primary somatosensory areas, supporting the existence of transcallosal transfer of tactile information. SIGNIFICANCE: This study provides valuable insights into the interhemispheric connections between primary sensory areas and underscore the potential role of interhemispheric interactions in somatosensory processing.
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Estimulación Eléctrica , Potenciales Evocados Somatosensoriales , Nervio Mediano , Inhibición Neural , Corteza Somatosensorial , Humanos , Nervio Mediano/fisiología , Masculino , Femenino , Corteza Somatosensorial/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Adulto , Estimulación Eléctrica/métodos , Inhibición Neural/fisiología , Adulto Joven , Lateralidad Funcional/fisiología , Electroencefalografía/métodosRESUMEN
A fundamental task for the brain is to generate predictions of future sensory inputs, and signal errors in these predictions. Many neurons have been shown to signal omitted stimuli during periodic stimulation, even in the retina. However, the mechanisms of this error signaling are unclear. Here we show that depressing inhibitory synapses shape the timing of the response to an omitted stimulus in the retina. While ganglion cells, the retinal output, responded to an omitted flash with a constant latency over many frequencies of the flash sequence, we found that this was not the case once inhibition was blocked. We built a simple circuit model and showed that depressing inhibitory synapses were a necessary component to reproduce our experimental findings. A new prediction of our model is that the accuracy of the constant latency requires a sufficient amount of flashes in the stimulus, which we could confirm experimentally. Depressing inhibitory synapses could thus be a key component to generate the predictive responses observed in the retina, and potentially in many brain areas.
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Células Ganglionares de la Retina , Sinapsis , Células Ganglionares de la Retina/fisiología , Sinapsis/fisiología , Animales , Estimulación Luminosa , Modelos Neurológicos , Retina/fisiología , Inhibición Neural/fisiología , RatonesRESUMEN
Sustained attention, as the basis of general cognitive ability, naturally varies across different time scales, spanning from hours, e.g. from wakefulness to drowsiness state, to seconds, e.g. trial-by-trail fluctuation in a task session. Whether there is a unified mechanism underneath such trans-scale variability remains unclear. Here we show that fluctuation of cortical excitation/inhibition (E/I) is a strong modulator to sustained attention in humans across time scales. First, we observed the ability to attend varied across different brain states (wakefulness, postprandial somnolence, sleep deprived), as well as within any single state with larger swings. Second, regardless of the time scale involved, we found highly attentive state was always linked to more balanced cortical E/I characterized by electroencephalography (EEG) features, while deviations from the balanced state led to temporal decline in attention, suggesting the fluctuation of cortical E/I as a common mechanism underneath trans-scale attentional variability. Furthermore, we found the variations of both sustained attention and cortical E/I indices exhibited fractal structure in the temporal domain, exhibiting features of self-similarity. Taken together, these results demonstrate that sustained attention naturally varies across different time scales in a more complex way than previously appreciated, with the cortical E/I as a shared neurophysiological modulator.
Asunto(s)
Atención , Corteza Cerebral , Electroencefalografía , Vigilia , Humanos , Atención/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Vigilia/fisiología , Corteza Cerebral/fisiología , Inhibición Neural/fisiología , Factores de Tiempo , Excitabilidad Cortical/fisiología , Privación de Sueño/fisiopatologíaRESUMEN
Midbrain dopamine neurons receive convergent synaptic input from multiple brain areas, which perturbs rhythmic pacemaking to produce the complex firing patterns observed in vivo. This study investigated the impact of single and multiple inhibitory inputs on ventral tegmental area (VTA) dopamine neuron firing in mice of both sexes using novel experimental measurements and modeling. We first measured unitary inhibitory postsynaptic currents produced by single axons using both minimal electrical stimulation and minimal optical stimulation of rostromedial tegmental nucleus and ventral pallidum afferents. We next determined the phase resetting curve, the reversal potential for GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs), and the average interspike membrane potential trajectory during pacemaking. We combined these data in a phase oscillator model of a VTA dopamine neuron, simulating the effects of unitary inhibitory postsynaptic conductances (uIPSGs) on spike timing and rate. The effect of a uIPSG on spike timing was predicted to vary according to its timing within the interspike interval or phase. Simulations were performed to predict the pause duration resulting from the synchronous arrival of multiple uIPSGs and the changes in firing rate and regularity produced by asynchronous uIPSGs. The model data suggest that asynchronous inhibition is more effective than synchronous inhibition, because it tends to hold the neuron at membrane potentials well positive to the IPSC reversal potential. Our results indicate that small fluctuations in the inhibitory synaptic input arriving from the many afferents to each dopamine neuron are sufficient to produce highly variable firing patterns, including pauses that have been implicated in reinforcement.