eNeuro最新文献

Short-term motor adaptation to novel movement dynamics has been shown to involve at least two concurrent learning processes: a slow process that responds weakly to error but retains information well, and a fast process that responds strongly to error but has poor retention. This modeling framework can explain several properties of motion-dependent motor adaptation (e.g., 24-hour retention). An important assumption of this computational framework is that learning is only based on the experienced movement error, and the effect of noise (either internally generated or externally applied) is not considered. We examined the respective error sensitivity by quantifying adaptation in three subject groups distinguished by the noise added to the motion-dependent perturbation (magnitudes of 0, 3 or 7N, at a frequency of 10 Hz, 20 subjects/group). We assessed the feedforward adaptive changes in motor output and examined the adaptation rate, retention and decay of learning. Applying a two-state modeling framework showed that the applied noise during training mainly affected the fast learning process, with the slow process largely unaffected; participants in the higher noise groups demonstrated a reduced force profile following training, but the decay rate across groups was similar, suggesting that the slow process was unimpaired across conditions. Collectively, our results provide evidence that noise significantly decreases motor adaptation, but this reduction may be due to its influence over specific learning mechanisms. Importantly, this may have implications for how the motor system compensates for random fluctuations, especially when affected by brain disorders that result in movement tremor (e.g., Essential Tremor).Significance statement Short-term motor adaptation to novel movement dynamics has been shown to involve at least two concurrent learning processes: a slow process that responds weakly to error but retains information well, and a fast process that responds strongly to error but has poor retention. This computational framework assumes that learning is only based on the movement error, and the effect of noise is not considered. We found that as the magnitude of externally-generated noise increased, the overall learning rate decreased. We found that this overall decrease in adaptation could be explained specifically by impairments to the fast learning process. The applied motor noise had little effect on the retention and decay of adaptation- aspects that mainly involve the slow learning process.

Social status and dominance are critical factors influencing well-being and survival across multiple species. However, dominance behaviors vary widely across species, from elaborate feather displays in birds to aggression in chimps. To effectively study dominance, it is essential to clearly define and reliably measure dominance behaviors. In laboratory settings, C57BL/6 mice are commonly used to study dominance due to their stable and linear social hierarchies. However, other mouse strains are also used for laboratory research. Despite substantial evidence for strain effects on behavioral repertoires, the impact of strain on dominance in mice remains largely unstudied. To address this gap, we compared dominance behaviors between CD1 and C57BL/6 male mice across four assays: observation of agonistic behaviors, urine marking, tube test, and a reward competition. We found that CD1 mice demonstrate increased fighting, increased territorial marking through urination, and increased pushing and resisting in the tube test. We used unsupervised machine learning and pose estimation data from the reward competitions to uncover behavioral differences across strains and across rank differences between competing pairs. Of the four assays, urine marking and agonistic behaviors showed the strongest correlation with dominance in both strains. Most notably, we found that CD1 dominance rankings based on the tube test negatively correlated with rankings from all three other assays, suggesting that the tube test may measure a different behavior in CD1 mice. Our results highlight that behaviors can be strain-specific in mice and studies that measure social rank should consider assays carefully to promote reproducibility.

Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuroimmune cell signaling, but their roles in specific behavioral responses are not fully elucidated. Voltage-gated Ca_V2.2 channel activity in skin controls rapid and transient heat hypersensitivity induced by intradermal (i.d.) capsaicin via IL-1ɑ cytokine signaling. Ca_V2.2 channels are not, however, involved in mechanical hypersensitivity that developed in the i.d. capsaicin animal model. Here, we show that Ca_V2.2 channels are also critical for heat hypersensitivity induced by i.d. complete Freund adjuvant (CFA). i.d. CFA, a model of chronic neuroinflammation, involves ongoing cytokine signaling for days leading to pronounced edema and hypersensitivity to sensory stimuli. Peripheral Ca_V2.2 channel activity in the skin was required for the full development and week-long time course of heat hypersensitivity induced by i.d. CFA, but paw edema and mechanical hypersensitivity were independent of Ca_V2.2 channel activity. CFA induced increases in several cytokines in hindpaw fluid including IL-6 which was also dependent on Ca_V2.2 channel activity. Using IL-6-specific neutralizing antibodies in vivo, we show that IL-6 contributes to heat hypersensitivity and that neutralizing both IL-1ɑ and IL-6 was even more effective at reducing the magnitude and duration of CFA-induced heat hypersensitivity. Our findings demonstrate a functional link between Ca_V2.2 channel activity and the release of IL-6 in the skin and show that Ca_V2.2 channels have a privileged role in the induction and maintenance of heat hypersensitivity during chronic forms of neuroinflammation in the skin.

The study of ideological asymmetries in empathy has consistently yielded inconclusive findings. Yet, until recently these inconsistencies relied exclusively on self-reports, which are known to be prone to biases and inaccuracies when evaluating empathy levels. Very recently, we reported ideological asymmetries in cognitive-affective empathy while relying on neuroimaging for the first time to address this question. In the present investigation which sampled a large cohort of human individuals from two distant countries and neuroimaging sites, we re-examine this question, but this time from the perspective of empathy to physical pain. The results are unambiguous at the neural and behavioral levels and showcase no asymmetry. This finding raises a novel premise: the question of whether empathy is ideologically asymmetrical depends on the targeted component of empathy (e.g., physical pain vs cognitive-affective) and requires explicit but also unobtrusive techniques for the measure of empathy. Moreover, the findings shed new light on another line of research investigating ideological (a)symmetries in physiological responses to vicarious pain, disgust, and threat.

Impulsive individuals excessively discount the value of delayed rewards, and this is thought to reflect deficits in brain regions critical for impulse control such as the anterior cingulate cortex (ACC). Delay discounting (DD) is an established measure of cognitive impulsivity, referring to the devaluation of rewards delayed in time. This study used male Wistar rats performing a DD task to test the hypothesis that neural activity states in ACC ensembles encode strategies that guide decision-making. Optogenetic silencing of ACC neurons exclusively increased impulsive choices at the 8 s delay by increasing the number of consecutive low-value, immediate choices. In contrast to shorter delays where animals preferred the delay option, no immediate or delay preference was detected at 8 s. These data suggest that ACC was critical for decisions requiring more deliberation between choice options. To address the role of ACC in this process, large-scale multiple single-unit recordings were performed and revealed that 4 and 8 s delays were associated with procedural versus deliberative neural encoding mechanisms, respectively. The 4 and 8 s delay differed in encoding of strategy corresponding to immediate and delay run termination. Specifically, neural ensemble states at 4 s were relatively stable throughout the choice but exhibited temporal evolution in state space during the choice epoch that resembled ramping during the 8 s delay. Collectively, these findings indicate that ensemble states in ACC facilitate strategies that guide decision-making, and impulsivity increases with disruptions of deliberative encoding mechanisms.

Neurodevelopmental abnormalities are considered to be one of the important causes of schizophrenia. The offspring of methylazoxymethanol acetate (MAM)-exposed mice are recognized for the dysregulation of neurodevelopment and are well-characterized with schizophrenia-like phenotypes. However, the inhibition-related properties of the medial prefrontal cortex (mPFC) and hippocampus throughout adolescence and adulthood have not been systematically elucidated. In this study, both 10 and 15 mg/kg MAM-exposed mice exhibited schizophrenia-related phenotypes in both adolescence and adulthood, including spontaneous locomotion hyperactivity and deficits in prepulse inhibition. We observed that there was an obvious parvalbumin (PV) loss in the mPFC and hippocampus of MAM-exposed mice, extending from adolescence to adulthood. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons at mPFC and hippocampus was significantly dampened in the 10 and 15 mg/kg MAM-exposed mice. Furthermore, the firing rate of putative pyramidal neurons in mPFC and hippocampus was increased, while that of putative inhibitory neurons was decreased during both adolescence and adulthood. In conclusion, PV loss in mPFC and hippocampus of MAM-exposed mice may contribute to the impaired inhibitory function leading to the attenuation of inhibition in the brain both in vitro and in vivo.

Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM; this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of nontarget responses (a.k.a. failure of feature binding, pNT). In Experiment 2 (N = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to misbinding (i.e., participants self-reported "remembered" in nontarget responses) or informed guessing trials (participants self-reported "forgotten" in nontarget responses). We replicated the main findings in Experiment 1 and observed greater tDCS effects of PPC on RT in informed guessing trials while there are comparable effects on pNT in these two types of trials. In Experiment 3 (N = 28), we then examined whether the tDCS effects over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provided direct causal evidence supporting the specific involvement of PPC in feature binding during VWM retrieval, from both aspects of speed and response preference, expanding our understanding of the neural basis of feature binding in VWM.

Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current (I _h). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs. Synaptic plasticity can bidirectionally modify dendritic HCN channels in excitatory neurons depending on the strength of synaptic potentiation. In inhibitory neurons, however, the dendritic expression and modulation of HCN channels are largely unknown. In this study, we systematically compared the modulation of I _h by synaptic potentiation in hippocampal CA1 pyramidal neurons and stratum radiatum (sRad) interneurons in mouse organotypic cultures. I _h properties were similar in inhibitory and excitatory neurons and contributed to resting membrane potential and action potential firing. We found that in sRad interneurons, HCN channels were downregulated after synaptic plasticity, irrespective of the strength of synaptic potentiation. This suggests differential regulation of I _h in excitatory and inhibitory neurons, possibly signifying their distinct role in network activity.