eNeuro最新文献

Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the MeCP2 gene, is characterized by cognitive and social deficits. Previous studies have noted hypoactivity in the medial prefrontal cortex (mPFC) pyramidal neurons of MeCP2-deficient mice (RTT mice) in response to both social and nonsocial stimuli. To further understand the neural mechanisms behind the social deficits of RTT mice, we monitored excitatory pyramidal neurons in the prelimbic region of the mPFC during social interactions in mice. These neurons' activity was closely linked to social preference, especially in wild-type mice. However, RTT mice showed reduced social interest and corresponding hypoactivity in these neurons, indicating that impaired mPFC activity contributes to their social deficits. We identified six mPFC neural ensembles selectively tuned to various stimuli, with RTT mice recruiting fewer neurons to ensembles responsive to social interactions and consistently showing lower stimulus-ON ensemble transient rates. Despite these lower rates, RTT mice exhibited an increase in the percentage of social-ON neurons in later sessions, suggesting a compensatory mechanism for the decreased firing rate. This highlights the limited plasticity in the mPFC caused by MeCP2 deficiency and offers insights into the neural dynamics of social encoding. The presence of multifunctional neurons and those specifically responsive to social or object stimuli in the mPFC emphasizes its crucial role in complex behaviors and cognitive functions, with selective neuron engagement suggesting efficiency in neural activation that optimizes responses to environmental stimuli.

Studies employing EEG to measure somatosensory responses have been typically optimized to compute event-related potentials in response to discrete events. However, tactile interactions involve continuous processing of nonstationary inputs that change in location, duration, and intensity. To fill this gap, this study aims to demonstrate the possibility of measuring the neural tracking of continuous and unpredictable tactile information. Twenty-seven young adults (females, 15) were continuously and passively stimulated with a random series of gentle brushes on single fingers of each hand, which were covered from view. Thus, tactile stimulations were unique for each participant and stimulated fingers. An encoding model measured the degree of synchronization between brain activity and continuous tactile input, generating a temporal response function (TRF). Brain topographies associated with the encoding of each finger stimulation showed a contralateral response at central sensors starting at 50 ms and peaking at ∼140 ms of lag, followed by a bilateral response at ∼240 ms. A series of analyses highlighted that reliable tactile TRF emerged after just 3 min of stimulation. Strikingly, topographical patterns of the TRF allowed discriminating digit lateralization across hands and digit representation within each hand. Our results demonstrated for the first time the possibility of using EEG to measure the neural tracking of a naturalistic, continuous, and unpredictable stimulation in the somatosensory domain. Crucially, this approach allows the study of brain activity following individualized, idiosyncratic tactile events to the fingers.

Social recognition is an essential part of social function and often promotes specific social behaviors based on prior experience. Social and defensive behaviors in particular often emerge with prior experiences of familiarity or novelty/stress, respectively. This is also commonly seen in rodents toward same-strain and interstrain conspecifics. Medial amygdala (MeA) activity guides social choice based on age and sex recognition and is sensitive to social experiences. However, little is known about whether the MeA exhibits differential responses based on strain or how this is impacted by experience. Social stress impacts posterior MeA (MeAp) function and can shift measures of social engagement. However, it is unclear how stress impacts MeAp activity and contributes to altered social behavior. The primary goal of this study in adult male Sprague Dawley rats was to determine whether prior stress experience with a different-strain (Long-Evans) rat impacts MeAp responses to same-strain and different-strain conspecifics in parallel with a change in behavior using in vivo fiber photometry. We found that MeAp activity was uniformly activated during social contact with a novel same-strain rat during a three-chamber social preference test following control handling but became biased toward a novel different-strain rat following social stress. Socially stressed rats also showed initially heightened social interaction with novel same-strain rats but showed social avoidance and fragmented social behavior with novel different-strain rats relative to controls. These results indicate that heightened MeAp activity may guide social responses to novel, threatening, rather than non-threatening, social stimuli after stress.

The goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordate Ciona are well-suited to make contributions in this area. In addition to having a described connectome, Ciona larvae have a range of readily quantified behaviors. Moreover, the small number of neurons in the larval CNS (∼180) holds the promise of a comprehensive characterization of individual neurons. We present single-neuron predictions for glutamate receptor (GlutR) expression based on in situ hybridization. Included are both ionotropic receptors (AMPA, NMDA, and kainate) and metabotropic receptors. The predicted glutamate receptor expression dataset is discussed in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The predicted expression of AMPA and NMDA receptors may help resolve issues regarding the co-production of GABA and glutamate by a subset of photoreceptors. The targets of these photoreceptors in the midbrain appear to express NMDA receptors, but not AMPA receptors. This is in agreement with previous results indicating that GABA is the primary neurotransmitter from the photoreceptors evoking a swimming response through a disinhibition mechanism and that glutamate may, therefore, have only a modulatory action in this circuit. Other findings reported here are more unexpected. For example, many of the targets of glutamatergic epidermal sensory neurons (ESNs) do not express any of the ionotropic receptors, yet the ESNs themselves express metabotropic receptors. Thus, we speculate that their production of glutamate may be for communication with neighboring ESNs, rather than to their interneuron targets.

Ca²⁺-binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca²⁺ sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previously hypothesized. Remarkably, mouse rods and human cones exclusively expressed CaBP4, whereas mouse cones and human rods coexpressed both CaBP4 and CaBP5. Our single-cell reverse transcription polymerase chain reaction analysis confirmed the coexpression CaBP1 and CaBP5 in individual RBs from mice of either sex. Additionally, all three splice variants of CaBP1, primarily L-CaBP1, were detected in mouse RBs. Taken together, our study offers a comprehensive overview of the distribution of CaBPs in mouse and human retinal neurons, providing valuable insights into their roles in visual functions.

Some visual neurons in the dragonfly (Hemicordulia tau) optic lobe respond to small, moving targets, likely underlying their fast pursuit of prey and conspecifics. In response to repetitive targets presented at short intervals, the spiking activity of these "small target motion detector" (STMD) neurons diminishes over time. Previous experiments limited this adaptation by including intertrial rest periods of varying durations. However, the characteristics of this effect have never been quantified. Here, using extracellular recording techniques lasting for several hours, we quantified both the spatial and temporal properties of STMD adaptation. We found that the time course of adaptation was variable across STMD units. In any one STMD, a repeated series led to more rapid adaptation, a minor accumulative effect more akin to habituation. Following an adapting stimulus, responses recovered quickly, though the rate of recovery decreased nonlinearly over time. We found that the region of adaptation is highly localized, with targets displaced by ∼2.5° eliciting a naive response. Higher frequencies of target stimulation converged to lower levels of sustained response activity. We determined that adaptation itself is a target-tuned property, not elicited by moving bars or luminance flicker. As STMD adaptation is a localized phenomenon, dependent on recent history, it is likely to play an important role in closed-loop behavior where a target is foveated in a localized region for extended periods of the pursuit duration.

Chemotherapy-related cognitive impairments (CRCIs) encompass cognitive deficits in memory, attention, and executive function that arise during and following chemotherapy. CRCI symptoms are predominantly reported by female cancer patients but also occur in males. These impairments may involve reduced estradiol levels, which then increases vulnerability to the impact of tumors and chemotherapy on cognition. This study utilized the MMTV-PyVT mouse model of breast cancer to test the hypothesis that impaired ovarian function and associated estradiol levels play a critical role in CRCI susceptibility. Mice were either ovariectomized (OVX) or underwent sham surgery. The OVX group then received supplemental estradiol (E²) ad libitum in the drinking water to maintain physiological hormone levels. After tumor development, mice were trained in the Morris water maze to assess spatial memory, and subsequently, they received weekly injections of either saline or a combination of cyclophosphamide (CYP; 66.7 mg/kg, i.v.) and doxorubicin (DOX; 6.7 mg/kg, i.v.) for 4 weeks. Spatial memory was reassessed 10 d and then 35 d, after the final injections. Results demonstrated a significant disruption of normal ovarian cycling in sham-operated mice treated with CYP + DOX, as well as significant spatial memory impairments when compared with OVX mice supplemented with E² This study suggests that chemotherapy-induced ovarian damage and the consequent drop in circulating estrogens significantly contribute to vulnerability to CRCIs, underscoring the importance of estradiol in mitigating CRCI risks.

Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experience remains persistent.

Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward masking requires inhibition from the superior paraolivary nucleus) is that this theory can explain forward masking observed in the brainstem, early in the ascending pathway. For explaining psychoacoustic results, one strength of this model is that it can account for the lack of elevation in thresholds observed when masker level is randomly varied from interval-to-interval, a result that is difficult to explain using the conventional temporal window model of psychophysical forward masking. Future directions for evaluating the efferent mechanism as a contributing mechanism for psychoacoustic results are discussed.

Retinitis pigmentosa (RP) is a family of genetically heterogeneous diseases still without a cure. Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the "bystander" degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role. Targeting these generalized biological processes represents a strategy to develop mutation-agnostic therapies for saving vision in large populations of RP individuals. A classical method to support neuronal survival is by employing neurotrophic factors, such as NGF. This study uses painless human NGF (hNGFp), a TrkA receptor-biased variant of the native molecule with lower affinity for nociceptors and limited activity as a pain inducer; the molecule has identical neurotrophic power of the native form but a reduced affinity for the p75NTR receptors, known to trigger apoptosis. hNGFp has a recognized activity on brain microglial cells, which are induced to a phenotype switch from a highly activated to a more homeostatic configuration. hNGFp was administered to RP-like mice in vivo with the aim of decreasing retinal inflammation and also providing retinal neuroprotection. However, the ability of this treatment to counteract the bystander degeneration of cones remained limited.