Journal of neurophysiology最新文献

The thalamic reticular nucleus (TRN) is a thin shell of gap junction-coupled GABAergic inhibitory neurons that regulate afferent sensory relay of the thalamus. The TRN receives dopaminergic innervation from the midbrain, and it is known to express high concentrations of D1 and D4 receptors. Although dopaminergic modulation of presynaptic inputs to TRN has been described, the direct effect of dopamine on TRN neurons and its electrical synapses is largely unknown. Here, we confirmed D1 and D4 expression and showed that D2 receptors are also expressed in TRN. To characterize how dopamine affects both neuronal excitability and electrical synapse coupling strength in the TRN, we performed dual whole cell patch-clamp recordings of TRN neurons and injected them with 500-ms current pulses to measure input resistance, rheobase, spiking frequency, and coupling conductance. Measurements were taken before and after bath application of dopamine or agonists for either D1, D2, or D4 receptors. Our results show that bath application of dopamine did not consistently modulate excitability or electrical synapse strength. However, application of specific dopamine receptor agonists revealed that activation of D1 and D4 receptors increases input resistance and activation of D2-like receptors lowers maximum tonic spike rate. Notably, D2 and D4 receptors depressed electrical synapses. Together, our results suggest that coactivation of D1, D2, and D4 receptors may result in cross talk due to opposing signaling cascades. Furthermore, we show that selective dopamine receptor engagement has substantial potential to modulate TRN circuitry.NEW & NOTEWORTHY Postsynaptic modulation of TRN neurons by activation of specific DA receptor subtypes has not been previously determined. Our research identifies that a previously unreported D2 receptor is expressed in TRN, and we found that D1, D2, and D4 receptors impose distinct excitability changes on TRN. Furthermore, D2 and D4 receptors depress electrical synapses in TRN, identifying a new substrate for modulation of intra-TRN communication.

In motor adaptation, learning is thought to rely on a combination of several processes. Two of these are implicit learning (incidental updating of the movement due to sensory prediction error) and explicit learning (intentional adjustment to reduce target error). The explicit component is thought to be fast adapting, whereas the implicit one is slow. The dynamic integration of such fast and slow components can lead to spontaneous recovery. That is, after prolonged adaptation of movement to a given perturbation, the learning is extinguished by presenting a perturbation in the opposite direction for a few trials. After such extinction, the learned adaptation can reappear in the absence of any further training, a phenomenon called spontaneous recovery. Trewartha et al. (Trewartha KM, Garcia A, Wolpert DM, Flanagan JR. J Neurosci 34: 13411-13421, 2014) found that older adults show less spontaneous recovery than their younger controls, indicating impairments in short-term retention of force-field adaptation. This disagrees with evidence suggesting that the implicit component and its retention do not decline with aging. To clarify this discrepancy, we performed a conceptual replication of that result. Twenty-eight healthy young and 20 healthy older adults learned to adapt to a forcefield perturbation in a paradigm known to elicit spontaneous recovery. Both groups adapted equally well to the perturbation. Implicit adaptation of the older subjects was indistinguishable from that of their younger counterparts. In addition, our conceptual replication failed to reproduce the result of Trewartha et al. (Trewartha KM, Garcia A, Wolpert DM, Flanagan JR. J Neurosci 34: 13411-13421, 2014) and found that the spontaneous recovery was also similar across groups. Our results reconcile previous studies by showing that both spontaneous recovery and implicit adaptation are unaffected by aging.NEW & NOTEWORTHY In this study, we tested whether aging influences the ability to learn to counteract a perturbation during reaching movements and to recall previously learned motor memories. In contrast to a previously published paper, we found that the ability of older participants to adapt to a perturbation and to recall motor memories remains unimpaired.

The primate dorsolateral prefrontal cortex (DLPFC) displays unique in vivo activity patterns, but how in vivo activity regulates DLPFC pyramidal neuron (PN) properties remains unclear. We assessed the effects of in vivo Kir2.1 overexpression, a genetic silencing tool, on synapses in monkey DLPFC PNs. We show for the first time that recombinant ion channel expression successfully modifies the excitability of primate cortex neurons, producing effects on synaptic properties apparently different from those in the rodent cortex.

Buprenorphine is an opioid approved for medication-assisted treatment of opioid use disorder. Used off-label, buprenorphine has been reported to contribute to the clinical management of anxiety. Although human anxiety is a highly prevalent disorder, anxiety is a latent construct that cannot be directly measured. The present study combined machine learning techniques and artificial intelligence with confirmatory factor analysis to evaluate the hypothesis that buprenorphine alters motor and anxiety-like behavior in C57BL/6J (B6) mice (n = 30) as a function of dose, sex, and body mass. After administration of saline (control) or buprenorphine, mice were placed on an elevated zero maze (EZM) for 5 min. Digital video of mouse behavior was uploaded to the cloud, and mouse position on the maze was tracked and analyzed with supervised machine learning and artificial intelligence. ANOVA and post hoc test showed that buprenorphine significantly altered five motor behaviors. Confirmatory factor analysis revealed that the latent construct of anxiety-like behavior accounted for a statistically significant amount of variance in all five motor behaviors.NEW & NOTEWORTHY Machine learning and pose estimation using a convolutional neural network accurately detected and objectively scored buprenorphine-induced changes in locomotor behaviors of mice on an elevated zero maze (EZM). Confirmatory factor analysis supports the interpretation that the anxiety-like construct accounted for the buprenorphine-induced changes in motor behavior. The results have noteworthy implications for the relationship between Darwin's story model of mammalian emotions and computational models of anxiety-like behavior in mice.

The medial amygdala (MeA) is activated by social stimuli and manipulations of the MeA disrupt a wide range of social behaviors. Social stress can shift social behaviors and may accomplish this partly via effects on the MeA. However, very little is known about the effects of social stress on the electrophysiological activity of MeA neurons. The posterior division of the MeA (MeAp) has been implicated in driving social engagement. We hypothesized that repeated social stress would cause parallel changes in in vivo activity of MeAp neurons and social behavior. The resident-intruder paradigm was used to produce repeated social stress in adult male rats. After repeated social stress, MeAp neurons were recorded with in vivo single-unit electrophysiology in anesthetized rats. MeAp neurons, specifically those in the posterodorsal subnucleus (MeApd), fired faster in stressed rats than in controls, and this effect was directly associated with stressor intensity. The MeAp sends dense projections to the posterior bed nucleus of stria terminalis (pBNST) and ventromedial hypothalamus (VMH), and both regions are essential for social engagement and are sensitive to social stressors. MeAp projections to pBNST had higher activity after stress, whereas projections to the VMH were not affected. These effects were significant only in rats that displayed susceptibility to this social stressor, as demonstrated by lower weight gain. Furthermore, the effect of stress on MeApd and MeAp-pBNST neuronal firing was correlated with lower social interaction. These results indicate that heightened MeApd and MeA-pBNST activity may contribute to alterations in social behaviors following social stress.NEW & NOTEWORTHY Social stress contributes to psychiatric disorders and impacts multiple brain regions. However, effects on a crucial area for social function, the medial amygdala (MeA), are unclear. We found that social stress increased firing of posterior MeA neurons, and particularly neurons that project to bed nucleus of the stria terminalis, a region implicated in anxiety. Effects of stress on this circuit were associated with diminished social interaction and help clarify how stress can impact social functions.

Voltage-sensitive calcium channels contribute to depolarization of both motor neurons and interneurons in animal studies, but less is known of their contribution to human motor control and whether blocking them has potential in future antispasmodic treatment in humans. Therefore, this study investigated the acute effect of nimodipine on the transmission of human spinal reflex pathways involved in spasticity. In a double-blinded, crossover study, we measured soleus muscle stretch reflexes and H reflexes and tibialis anterior cutaneous reflexes in 19 healthy subjects before and after nimodipine (tablet 60 mg) or baclofen (tablet 25 mg). Baclofen was used as a control to compare nimodipine's effects with known antispastic treatment. Changes in the size of the maximum H reflex (H_max)/maximum direct motor response in muscle (M_max) ratio and stretch and cutaneous reflexes following intervention with nimodipine and baclofen, respectively, were analyzed with a one-way repeated-measures (RM) ANOVA. Nimodipine significantly reduced the H_max/M_max ratio [F(2.5,42) = 15; P < 0.0001] and the normalized soleus stretch reflex [F(2.6,47) = 4.8; P = 0.0073] after administration. A similar tendency was seen after baclofen [H_max/M_max ratio: F(2.1,39) = 4.0, P = 0.024; normalized stretch reflex: F(2.8,50) = 2.4; P = 0.083]. The M_max response was unaffected by either intervention. Interestingly, during voluntary soleus activation, the stretch reflex remained unchanged with either treatment. For the cutaneous reflexes, there was a trend toward reduced early inhibition [F(1.6,9.3) = 4.5; P = 0.050] and subsequent facilitation [F(1.3,8.0) = 4.3; P = 0.065] after nimodipine. No severe adverse effects were reported after nimodipine. These findings suggest that nimodipine acutely reduced electrophysiological measures related to spasticity in healthy individuals. The effect seemed located at the spinal level, and voluntary contraction counterbalanced the reduction of the stretch reflex, highlighting its relevance for future studies on antispastic therapies.NEW & NOTEWORTHY The calcium channel antagonist nimodipine significantly reduces the size of the soleus H reflex and stretch reflex in healthy individuals without affecting maximum direct motor response (M_max) or the stretch reflex during voluntary activation. This underscores the importance of exploring nimodipine as a potential antispastic medication in the future.

Our knowledge of human sensorimotor learning and memory is predominantly based on the visuospatial workspace and limb movements. Humans also have a remarkable ability to produce and perceive speech sounds. We asked whether the human speech-auditory system could serve as a model to characterize the retention of sensorimotor memory in a workspace that is functionally independent of the visuospatial one. Using adaptation to altered auditory feedback, we investigated the durability of a newly acquired speech-acoustical memory (8- and 24-h delay), its sensitivity to the manner of acquisition (abrupt vs. gradual perturbation), and factors affecting memory retrieval. We observed extensive retention of learning (∼70%) but found no evidence for offline gains. The speech-acoustical memory was insensitive to the manner of its acquisition. To assess factors affecting memory retrieval, tests were first done in the absence of auditory feedback (with masking noise). Under these conditions, it appeared there was no memory for prior learning as if after an overnight delay, speakers had returned to their habitual speech production modes. However, when speech was reintroduced, resulting in speech error feedback, speakers returned immediately to their fully adapted state. This rapid switch shows that the two modes of speech production (adapted and habitual) can coexist in parallel in sensorimotor memory. The findings demonstrate extensive persistence of speech-acoustical memory and reveal context-specific memory retrieval processes in speech-motor learning. We conclude that the human speech-auditory system can be used to characterize sensorimotor memory in a workspace that is distinct from the visuospatial workspace.NEW & NOTEWORTHY There is extensive retention of speech-motor learning. Two parallel modes exist in speech motor memory, one with access to everyday habitual speech and the other with access to newly learned speech-acoustical maps. The availability of speech error feedback triggers a switch between these two modes. Properties of sensorimotor memory in the human speech-auditory system are behaviorally similar to, but functionally independent of, their visuospatial counterparts.

Purposeful movement often requires selection of a particular action from a range of alternatives, but how does the brain represent potential actions so that they can be compared for selection, and how are motor commands generated if movement is initiated before the final goal is identified? According to one hypothesis, the brain averages partially prepared motor plans to generate movement when there is goal uncertainty. This is consistent with the idea that motor decision-making unfolds through competition between internal representations of alternative actions. An alternative hypothesis holds that only one movement, which is optimized for task performance, is prepared for execution at any time. Under this conception, decisions about the best motor goal given current information are completed upstream from neural circuits that perform motor planning. To distinguish between these hypotheses, we modified an experiment (Alhussein L, Smith MA. eLife 10: e67019, 2021) in which participants had to start reaching toward targets associated with opposite curl force fields before knowing the correct target to reach. Crucially, we forced the participants to initiate movement immediately after target presentation (i.e., mean reaction times ∼250 ms) so that they had limited opportunity to deliberate between the available alternatives. We found that the reaching dynamics reflected only those learned for the selected reach direction, rather than a combination of those for the alternative targets presented, irrespective of the time available to initiate movement. The data are consistent with the conclusion that reaching dynamics were specified downstream of action selection under the target uncertainty conditions of this study.NEW & NOTEWORTHY Here we found no evidence of "motor averaging" of reach dynamics for multiple potential actions when people had to respond as quickly as possible to uncertain target location cues. People exerted forces appropriate for the specific reach direction they selected irrespective of movement initiation time, suggesting that reaching dynamics were specified downstream of action selection.

We present a case report of a 42-year-old female with post-West Nile virus meningoencephalitis who exhibited unique, long-latency diaphragm potentials evoked by transcranial and cervical magnetic stimulation after exposure to acute intermittent hypoxia (AIH). The subject was recruited for a study investigating AIH effects on respiratory motor function in healthy individuals. She had contracted West Nile virus infection 5 years before assessment that resulted in hospitalization and persistent allodynia but was not reported to the research team. During the study, transcranial (TMS) and cervical (CMS) magnetic stimulation were performed before and 30-60 min after a single presentation of AIH [15, 1-min hypoxic episodes (∼9% inspired O₂), with 1-min normoxic intervals]. Diaphragm EMG was recorded using chest wall surface electrodes. At baseline, evoked diaphragm potentials were within normal ranges for both TMS (onset latency = 17.0 ± 1.1 ms; peak-to-peak amplitude = 220 ± 27 µV) and CMS (onset latency = 7.8 ± 0.6 ms; peak-to-peak amplitude = 336 ± 8 µV). However, long-latency TMS- and CMS-evoked potentials were observed 30-60 min post-AIH that were not present at baseline nor in healthy subjects. The onset of long-latency potentials ranged from 50 to 808 ms. While AIH is a potentially useful therapeutic strategy to enhance motor function after neurological disease or injury, it may elicit distinct effects in individuals with a history of neuroinfectious disease. Possible explanations for these unusual responses are discussed.NEW & NOTEWORTHY A 42-year-old female with post-West Nile virus meningoencephalitis demonstrated long-latency diaphragmatic potentials evoked by transcranial and cervical magnetic stimulation following exposure to acute intermittent hypoxia that were not present at baseline nor in healthy subjects. Although the cause of long-latency responses is unknown, we discuss possible mechanisms whereby acute intermittent hypoxia could create unique effects on the diaphragm/phrenic motor system in individuals with a history of neuroinfectious disease.

How humans perceive the texture of a surface can inform and guide how their interaction takes place. From grasping a glass to walking on icy steps, the information we gather from the surfaces we interact with is instrumental to the success of our movements. However, the hands and feet differ in their ability to explore and identify textures. Higher concentrations of mechanoreceptors in the fingertips provide tactile information to help modulate force and grip whereas the receptors of the feet help to inform surface texture and aid in balance. Cleland et al. (J Neurophysiol 132: 643-652, 2024), explores the relationship between texture perception, mode of exploration, and region of body used to explore said texture (hands vs. feet). This research is especially important in the context of understanding how texture perception affects stability, how hands and feet differ in their management and execution of tasks, and how this is adjusted in special populations of visually impaired individuals.