eNeuro最新文献

Maintenance of normal structure of the enteric nervous system (ENS), which regulates key gastrointestinal functions, requires robust homeostatic mechanisms, since by virtue of its location within the gut wall, the ENS is subject to constant mechanical, chemical, and biological stressors. Using transgenic and thymidine analogue-based experiments, we previously discovered that neuronal turnover - where continual neurogenesis offsets ongoing neuronal loss at steady state - represents one such mechanism. Although other studies confirmed that neuronal death continues into adulthood in the myenteric plexus of the enteric nervous system (ENS), the complicated nature of thymidine analogue presents challenges in substantiating the occurrence of adult neurogenesis. Therefore, it's vital to employ alternative, well-recognized techniques to substantiate the existence of adult enteric neurogenesis in the healthy gut. Here, by using established methods of assessing nuclear DNA content and detecting known mitotic marker phosphor-histone H3 (pH3) in Hu⁺ adult ENS cells, we show that ∼10% of adult small intestinal myenteric Hu⁺ cells in mice, and ∼20% of adult human small intestinal myenteric Hu⁺ cells show evidence of mitosis and hence are cycling neuroblasts. We observe that proportions of Hu⁺ cycling neuroblasts in the adult murine ENS neither vary with ganglia size, nor do they differ significantly between two intestinal regions - duodenum and ileum, or between sexes. Confocal microscopy provides further evidence of cytokinesis in Hu⁺ cells. The presence of a significant population of cycling neuroblasts in adult ENS provide further evidence of steady state neurogenesis in the adult ENS.Significance statement Using 3-dimensional confocal microscopy, immunohistochemical detection of cell cycle marker phosphor-Histone H3, and DNA content assessments using flow cytometry in Hu+ cells from adult small intestinal murine myenteric plexus, we show that ∼10% of myenteric Hu+ cells in adult gut are mitotic neuroblasts, whose proportional representation does not significantly differ between sexes or small intestinal regions. We further test and observe mitotic marker pH3 also immunolabels ∼23% of adult human myenteric Hu+ cells suggesting that presence of mitotic neuroblasts also extends to the adult human gut. These data further evidence of steady state adult enteric neurogenesis in the healthy gut and provide important cellular details in understanding how precursor cells continually generate large numbers of adult neurons in healthy gut.

Growth hormone (GH) is a neuromodulator that binds to receptors in the hippocampus and alters synaptic plasticity. A decline in GH levels is associated with normal aging, stress, and disease, and the mechanisms proposed involve the hippocampal circuit plasticity. To see how GH affects the hippocampal neural code, we recorded single neurons in the CA1 region of male Long-Evans rats with locally altered GH levels. Rats received injections of adeno-associated viruses into the hippocampus to make the cells overexpress either GH or an antagonizing mutated GH (aGH). Place cells were recorded in both familiar and novel environments to allow the assessment of pattern separation in the neural representations termed remapping. All the animals showed intact and stable place fields in the familiar environment. In the novel environment, aGH transfection increased the average firing rate, peak rate, and information density of the CA1 place fields. The tendency of global remapping increased in the GH animals compared with the controls, and only place cells of control animals showed significant rate remapping. Our results suggest that GH increases hippocampal sensitivity to novel information. Our findings show that GH is a significant neuromodulator in the hippocampus affecting how place cells represent the environment. These results could help us to understand the mechanisms behind memory impairments in GH deficiency as well as in normal aging.

Electrophysiology recordings from the brain using laminar multielectrode arrays allow researchers to measure the activity of many neurons simultaneously. However, laminar microelectrode arrays move relative to their surrounding neural tissue for a variety of reasons, such as pulsation, changes in intracranial pressure, and decompression of neural tissue after insertion. Inferring and correcting for this motion stabilizes the recording and is critical to identify and track single neurons across time. Such motion correction is a preprocessing step of standard spike sorting methods. However, estimating motion robustly and accurately in electrophysiology recordings is challenging due to the stochasticity of the neural data. To tackle this problem, we introduce MEDiCINe (Motion Estimation by Distributional Contrastive Inference for Neurophysiology), a novel motion estimation method. We show that MEDiCINe outperforms existing motion estimation methods on an extensive suite of simulated neurophysiology recordings and leads to more accurate spike sorting. We also show that MEDiCINe accurately estimates the motion in primate and rodent electrophysiology recordings with a variety of motion and stability statistics. We open-source MEDiCINe, usage instructions, examples integrating MEDiCINe with common tools for spike-sorting, and data and code for reproducing our results. This open software will enable other researchers to use MEDiCINe to improve spike sorting results and get the most out of their electrophysiology datasets.Significance Statement Recent advances in high-density microelectrode arrays such as Neuropixels have allowed neurophysiologists to record from hundreds of neurons simultaneously. Such data scale necessitates automatic isolation and tracking of individual neurons throughout a recording session, a process called "spike sorting". One challenge for automated spike sorting algorithms is relative motion between the electrodes and the brain, which must be corrected to stabilize the recording. We introduce a method for estimating such motion in neural recordings. Our method outperforms existing motion estimation methods and produces more accurate spike sorting on a benchmark of simulated datasets with known ground-truth motion. Our method also performs well on primate neurophysiology datasets. We open-source our method and instructions for integrating it into common spike sorting pipelines.

The role of sleep in memory consolidation is a widely discussed but still debated area of research. In light of the fact that memory consolidation during sleep is an evolutionary adaptive function, investigating the same phenomenon in nonhuman model species is highly relevant for its understanding. One such species, which has acquired human-analog sociocognitive skills through convergent evolution, is the domestic dog. Family dogs have surfaced as an outstanding animal model in sleep research, and their learning skills (in a social context) are subject to sleep-dependent memory consolidation. These results, however, are correlational, and the next challenge is to establish causality. In the present study, we aimed to adapt a TMR (targeted memory reactivation) paradigm in dogs and investigate its effect on sleep parameters. Dogs (N = 16) learned new commands associated with different locations and afterward took part in a sleep polysomnography recording when they were re-exposed to one of the previously learned commands. The results did not indicate a cueing benefit on choice performance. However, there was evidence for a decrease in choice latency after sleep, while the density (occurrence/minute) of fast sleep spindles was also notably higher during TMR recordings than adaptation recordings from the same animals and even compared with a larger reference sample from a previous work. Our study provides empirical evidence that TMR is feasible with family dogs, even during a daytime nap. Furthermore, the present study highlights several methodological and conceptual challenges for future research.

Extended performance of cognitively demanding tasks induces cognitive fatigue manifested with an overall deterioration of behavioral performance. In particular, long practice with tasks requiring impulse control is typically followed by a decrease in self-control efficiency, leading to performance instability. Here, we show that this is due to changes in activation modalities of key task-related areas occurring if these areas previously underwent intensive use. We investigated in 25 healthy adults the effects of extended practice with high cognitive demand (HCD) tasks on a Go-No Go task and the underlying electroencephalographic (EEG) activity. We compared these effects with those induced by practice with similar, but low cognitive demand (LCD) tasks. HCD tasks were followed by an increase in response inhibition failures. These were correlated with the appearance of a distinct neural signature on fast response trials, characterized by lower levels of beta ([13-30] Hz) EEG activity in the prestimulus period, and by a lack of EEG markers of preresponse processing in frontal areas. Moreover, HCD tasks were followed by a decrease in N200 during correct withholds while LCD tasks were followed instead by a lesser fraction of hits and a decrease in P300, suggesting a decrease in engagement. Overall, these results show that exertion of cognitive control determines the appearance of two distinct modalities of response with different processing speeds, associated with distinct underlying neural activity.

Functional imaging studies indicate that both the assessment of a person as untrustworthy as well as the assumption that a person has a sexually transmitted infection are associated with activation in regions of the salience network. However, studies are missing that combine these aspects and investigate the perceived trustworthiness of individuals previously assessed with high or low probability of a sexually transmitted infection.During fMRI measurements, 25 participants viewed photographs of people pre-classified as having high or low HIV probability and judged their trustworthiness. In a post-rating, stimuli were rated for trustworthiness, attractiveness and HIV probability.Persons pre-classified as HIV- in contrast to those pre-classified as HIV+ were rated more trustworthy and with lower HIV probability. Activation in medial orbitofrontal cortex was higher for those rated and pre-classified as HIV- than HIV+. Based on the individual ratings, but not the pre-classification, there was significantly higher activation in Insula, amygdala, anterior cingulate cortex and Nucleus accumbens in response to untrustworthy than to trustworthy faces.Activation of the salience network occurred when a person was judged as untrustworthy, but not according to a pre-classification. Activation in the medial orbitofrontal cortex, a structure associated with reward was enhanced when a person was perceived as trustworthy, and also when a person was pre-classified with low HIV probability. Our findings suggest that trustworthiness and HIV- perception have consistency across samples, while the perception of risk and associated activation of the salience network has restricted cross-sample consistency.Significance Statement Whether a person is trustworthy or might pose a risk to one's own health must be decided in a few moments and based on limited characteristics. The salience network as an "alarm system" should be involved in these evaluative processes. This paper reports the results of neural activation in trustworthiness judgments of naturalistic stimuli of persons pre-categorized as HIV+ or HIV-. We find activation in medial orbitofrontal cortex for people evaluated as trustworthy and for people pre-categorized as HIV-. For people judged as untrustworthy, activation in insula, amygdala, anterior cingulate cortex and Nucleus accumbens is revealed. These findings suggest a safety signal in the medial orbitofrontal cortex and an involvement of the salience network in risk detection.

Evolutionary pressures adapted insect chemosensation to their respective physiological needs and tasks in their ecological niches. Solitary nocturnal moths rely on their acute olfactory sense to find mates at night. Pheromones are detected with maximized sensitivity and high temporal resolution through mechanisms that are mostly unknown. While the inverse topology of insect olfactory receptors and heteromerization with the coreceptor Orco suggest ionotropic transduction via odorant-gated receptor-ion channel complexes, contradictory data propose amplifying G protein-coupled transduction. Here, we used in vivo tip-recordings of pheromone-sensitive sensilla of male Manduca sexta hawkmoths at specific times of day (rest vs. activity). Since the olfactory receptor neurons distinguish signal parameters in three consecutive temporal windows of their pheromone response (phasic; tonic; late, long-lasting), respective response parameters were analyzed separately. Disruption of G protein-coupled transduction and block of phospholipase C decreased and slowed the phasic response component during the activity phase of hawkmoths without affecting any other component of the response during activity and rest. A more targeted disruption of G_α subunits by blocking G_αo or sustained activation of G_αs using bacterial toxins affected the phasic pheromone response, while toxins targeting G_αq and G_α12/13 were ineffective. Consistent with these data, the expression of phospholipase Cβ4 depended on zeitgeber time, which indicates circadian clock-modulated metabotropic pheromone transduction cascades that maximize sensitivity and temporal resolution of pheromone transduction during the hawkmoth's activity phase. Thus, discrepancies in the literature on insect olfaction may be resolved by considering circadian timing and the distinct odor response components.Significance statement Insect chemosensory transduction is typically thought to be ionotropic, but data from different insect species suggests that metabotropic olfactory signaling may occur, either alongside or instead of ionotropic mechanisms. Nocturnal moths, known for their extraordinarily sensitive pheromone-detecting olfactory receptor neurons, likely use metabotropic signal amplification. To overcome limitations of previous in vitro studies, we conducted tip-recordings of pheromone-sensitive sensilla in healthy hawkmoths at specific zeitgeber times. Disrupting G protein signaling and phospholipase Cβ reduced sensitivity and altered response kinetics, revealing strict temporal control of transduction. Thus, contradictory findings in insect olfaction may be reconciled by considering diverse evolutionary pressures for distinct chemosensory signals in different species, zeitgeber time, and disparate odor response parameters.

Inner speech refers to the silent production of language in one's mind. As a purely mental action without obvious physical manifestations, inner speech has been notoriously difficult to quantify. To address this issue, the present study repurposed the phenomenon of speaking-induced suppression, wherein overt speech has been consistently shown to elicit reduced auditory evoked potentials compared with externally generated speech, as well as changes in oscillatory activity in gamma and theta frequency bands. Given the functional similarities between inner and overt speech, we used an established experimental protocol to investigate whether similar metrics could be used to distinguish the content of inner speech. Healthy participants (n = 129) produced an inner syllable at a precisely specified time. An audible syllable was concurrently presented which either matched or mismatched the content of the inner syllable. The results revealed that Match and Mismatch conditions could be differentiated on the basis of their evoked oscillations in the gamma, theta, and alpha bands. Notably, there was a gamma-band oscillation in the vicinity of the P2 that differed between the Match and Mismatch conditions, suggesting that "late" gamma-band activity may index consciously perceived expectancy violations, or cognitive prediction errors. Regarding the auditory evoked potentials, the N1 component was suppressed in the Match condition while the P2 component was suppressed in the Mismatch condition, replicating previous findings. This study provides support for the existence of "inner speaking-induced suppression", and demonstrates that inner syllables can be differentiated based on their influence on the electroencephalographic activity elicited by simultaneously-presented audible syllables.

High-frequency stimulation (HFS)-induced long-term potentiation (LTP) is generally regarded as a homosynaptic Hebbian-type LTP, where synaptic changes are thought to occur at the synapses that project from the stimulation site and terminate onto the neurons at the recording site. In this study, we first investigated HFS-induced LTP on urethane-anesthetized rats and found that cortical HFS enhances neural responses at the recording site through the strengthening of local connectivity with nearby neurons at the stimulation site rather than through synaptic strengthening at the recording site. This enhanced local connectivity at the stimulation site leads to increased output propagation, resulting in signal potentiation at the recording site. Additionally, we discovered that HFS can also nonspecifically strengthen distant afferent synapses at the HFS site, thereby expanding its impact beyond local neural connections. This form of plasticity exhibits a neo-Hebbian characteristic as it exclusively manifests in the presence of cholecystokinin release, induced by HFS. The cortical HFS-induced local LTP was further supported by a behavioral task, providing additional evidence. Our results unveil a previously overlooked mechanism underlying cortical plasticity: synaptic plasticity is more likely to occur around the soma site of strongly activated cortical neurons rather than solely at their projection terminals.

Functional ultrasound (fUS) imaging is a well-established neuroimaging technology that offers high spatiotemporal resolution and a large field of view. Typical strategies for analysing fUS data comprise either region-based averaging, typically based on reference atlases, or correlation with experimental events. Nevertheless, these methodologies possess several inherent limitations, including a restricted utilisation of the spatial dimension and a pronounced bias influenced by preconceived notions about the recorded activity. In this study, we put forth single-voxel clustering as a third method to address these issues. A comparison was conducted between the three strategies on a typical dataset comprising visually evoked activity in the superior colliculus in awake mice. The application of single-voxel clustering yielded the generation of detailed activity maps, which revealed a consistent layout of activity and a clear separation between haemodynamic responses. This method is best considered as a complement to region-based averaging and correlation. It has direct applicability to challenging contexts, such as paradigm-free analysis on behaving subjects and brain decoding.Significance Statement The application of spatiotemporal clustering at single-voxel resolution for functional ultrasound (fUS) signal analysis significantly enhances sensitivity in comparison to conventional methods, such as region-based averaging or event correlation. Conventional approaches frequently rely on predefined atlases or specific experimental conditions, which inherently restrict spatiotemporal resolution. In contrast, single-voxel clustering optimises the potential of fUS, facilitating the detection of intricate activity patterns throughout the brain without the necessity for prior assumptions. This approach enables more precise differentiation of hemodynamic responses and more reliable activity mapping. It is particularly advantageous in complex or paradigm-free studies, offering a high-resolution alternative to standard techniques.