eNeuro最新文献

The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy (GDX) on later evoked dopamine release in male Mus spicilegus, a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts dopamine neuron function in M. spicilegus males, we removed the gonads prepubertally at postnatal day (P)25 and then examined evoked dopamine release in the dorsomedial, dorsolateral (DLS), and nucleus accumbens core regions of striatal slices at P60-70 (late adolescence/early adulthood). To measure dopamine release, we used near-infrared catecholamine nanosensors which enable study of spatial distribution of dopamine release. We found that prepubertal GDX led to a significantly reduced density of dopamine release sites and reduced dopamine release at each site in the DLS nigrostriatal system compared with sham controls. In contrast, mesoaccumbal dopamine release was comparable between sham and gonadectomized groups. Our data suggest that during adolescence, the development of the nigrostriatal dopamine system is significantly affected by the rise in gonadal hormones in males, while the mesoaccumbal system shows no detectable sensitivity at this time point. These data are consistent with molecular studies in rodents that suggest nigrostriatal neurons are sensitive to androgens at puberty and extend our understanding of how gonadal hormones could impact the spatial distribution and release potential of dopamine terminals in the striatum.

Speech in everyday life is often masked by background noise, making comprehension effortful. Characterizing brain activity patterns when individuals listen to masked speech can help clarify the mechanisms underlying such effort. In the current study, we used functional magnetic resonance imaging (fMRI) in humans of either sex to investigate how neural signatures of story listening change in the presence of masking noise. We show that, as speech masking increases, spatial and temporal activation patterns in auditory regions become more idiosyncratic to each listener. In contrast, spatial activity patterns in brain networks linked to effort (e.g., cingulo-opercular network) are more similar across listeners when speech is highly masked and less intelligible, suggesting shared neural processes. Moreover, at times during stories when one meaningful event ended and another began, neural activation increased in frontal, parietal, and medial cortices. This event-boundary response appeared little affected by background noise, suggesting that listeners process meaningful units and, in turn, the gist of naturalistic, continuous speech even when it is masked somewhat by background noise. The current data may indicate that people stay engaged and cognitive processes associated with naturalistic speech processing remain intact under moderate levels of noise, whereas auditory processing becomes more idiosyncratic to each listener.

The chemokine CXCL12 plays critical roles in the development of the hippocampus dentate gyrus during both embryogenesis and adulthood. While multiple cell types in the hippocampus express Cxcl12, their individual contributions to the dentate gyrus development and function remain unclear. Here, using Cxcl12 reporter mice of both sexes, we characterize Cxcl12 expression in Cajal-Retzius (CR) cells-neurons that guide dentate gyrus morphogenesis and influence hippocampal circuitry. We show that CR cells prominently express Cxcl12 during early postnatal development, although both the number and proportion of Cxcl12-expressing CR cells decline significantly in adulthood. Notably, partial deletion of Cxcl12 from hippocampal CR cells in male and female mice does not result in detectable changes in dentate gyrus architecture, adult neurogenesis, or specific behaviors. These findings suggest that CR cell-derived CXCL12 may be less critical for dentate gyrus development than previously assumed and underscore the complexity and potential redundancy of CXCL12 signaling in the hippocampus.

Natural environments contain behaviorally-relevant information along many stimulus dimensions, each of which sensory systems must encode in order to guide behaviors. For example, mammalian visual cortex encodes features of visual scenes such as spatial information related to object identity and temporal information about the motion of those objects in space. In order to reliably encode these behaviorally-relevant visual features, neural representations should be robust to changes in environmental conditions. Further, information about changes in environmental conditions, such as the luminance changes that occur over the course of a day, are also important for guiding behaviors. In this study, we asked whether mouse primary visual cortex (V1) jointly represents the spatial properties of visual stimuli along with changes in the mean luminance of the visual scene. We find that while V1 neurons, in mice of either sex, encode spatial aspects of visual information in an invariant manner across luminance conditions, the V1 population response also contains a robust representation of luminance. Importantly, V1 populations encode changes in stimulus orientation and mean luminance along orthogonal axes in the neural response space, such that a change in one stimulus variable is encoded independently from the other.Significance Statement We recorded from neural populations in mouse V1 with two-photon imaging to examine how sensory information along multiple feature axes is distributed across the responses of diversely tuned neurons. We find that the V1 population response contains a representation of mean luminance in addition to maintaining a luminance-invariant spatial representation. These independent representations are possible because stimulus information is distributed randomly across the V1 population, such that changes in each stimulus variable are encoded along orthogonal axes in the neural response space. This study offers an example of how multi-dimensional sensory representations emerge from the diverse response properties of neocortical neurons.

Non-rapid eye movement (NREM) sleep is characterized by the interaction of multiple oscillations essential for memory consolidation, alongside a dynamic arrhythmic 1/f scale-free background that may also contribute to its functions. Recent spectral parametrization methods, such as FOOOF (Fitting-One-and-Over-f) and IRASA, enable the dissociation of rhythmic and arrhythmic components in the spectral domain; however, they do not resolve these processes in the time domain. Instantaneous measures of frequency, amplitude, and phase-amplitude coupling are thus still confounded by fluctuations in arrhythmic activity. This limitation represents a significant pitfall for studies of NREM sleep, often relying on instantaneous estimates to investigate the coupling of specific oscillations. To address this limitation, we introduce 'Rhythms & Background' (RnB), a novel wavelet-based methodology designed to dynamically denoise time-series data of arrhythmic interference. This enables the extraction of purely rhythmic time series, suitable for enhanced time-domain analyses of sleep rhythms. We first validate RnB through simulations, demonstrating its robust performance in accurately estimating spectral profiles of individual and multiple oscillations across a range of arrhythmic conditions. We then apply RnB to publicly available intracranial EEG sleep recordings, showing that it provides an improved spectral and time-domain representation of hallmark NREM rhythms. Finally, we demonstrate that RnB significantly enhances the assessment of phase-amplitude coupling between cardinal NREM oscillations, outperforming traditional methods that conflate rhythmic and arrhythmic components. This methodological advance offers a substantial improvement in the analysis of sleep oscillations, providing greater precision in the study of rhythmic activity critical to NREM sleep functions.Significance statement The Rhythms and Background (RnB) algorithm introduces a novel approach to signal processing in electrophysiology by disentangling rhythmic activity from the arrhythmic background at the time-series level. RnB denoise brain rhythms from arrhythmic interference in both the time and spectral domains, providing clearer insights into cerebral oscillatory processes. This breakthrough has direct applications in studying brain connectivity and oscillatory dynamics during sleep. Additionally, its application in clinical populations where pathological changes in arrhythmic activity are common, such as neurodevelopmental and neurodegenerative disorders, will help to better understand abnormal oscillatory processes. By improving the accuracy of rhythmic signal analysis, RnB opens new avenues for understanding brain function and dysfunction in research and clinical settings.

An exciting aspect of neuroscience is developing and testing hypotheses via experimentation. However, due to logistical and financial hurdles, the experiment and discovery component of neuroscience is generally lacking in classroom and outreach settings. To address this issue, here we introduce RetINaBox: a low-cost open-source electronic visual system simulator that provides users with a hands-on tool to discover how the visual system builds feature detectors. RetINaBox includes an LED array for generating visual stimuli and photodiodes that act as an array of model photoreceptors. Custom software on a Raspberry Pi computer reads out responses from model photoreceptors and allows users to control the polarity and delay of the signal transfer from model photoreceptors to model retinal ganglion cells. Interactive lesson plans are provided, guiding users to discover different types of visual feature detectors-including ON/OFF, center-surround, orientation-selective, and direction-selective receptive fields-as well as their underlying circuit computations.

Autism spectrum disorder, schizophrenia, and bipolar disorder are neuropsychiatric conditions that manifest early in life with a wide range of phenotypes, including repetitive behavior, agitation, and anxiety ( American Psychological Association, 2013). While the etiology of these disorders is incompletely understood, recent data implicate a role for mitochondrial dysfunction ( Norkett et al., 2017; Khaliulin et al., 2025). Mitochondria translocate to intracellular compartments to support energetics and free-radical buffering; failure to achieve this localization results in cellular dysfunction ( Picard et al., 2016). Mitochondrial Rho-GTPase 1 (Miro1) resides on the outer mitochondrial membrane and facilitates microtubule-mediated mitochondrial motility ( Fransson et al., 2003). The loss of MIRO1 is reported to contribute to the onset/progression of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease ( Kay et al., 2018). We have hypothesized that MIRO1 also has a role in nervous system development ( Lin-Hendel et al., 2016). To test this, we ablated Miro1 from cortical excitatory progenitors by crossing floxed Miro1 mice with Emx1-Cre mice and studied mice of both sex. We found that mitochondrial mislocalization in migrating excitatory neurons was associated with reduced brain weight, decreased cortical volume, and subtle cortical disorganization. Adult Miro1 conditional mutants exhibit agitative-like behaviors, including decreased nesting and abnormal home cage activity. The mice exhibited anxiety-like behavior and avoided confined spaces, features that have been linked to several human behavioral disorders. Our data link MIRO1 function with mitochondrial dynamics in the pathogenesis of several neuropsychiatric disorders and implicate intracellular mitochondrial dynamics to several anxiety-like behaviors.

Alcohol use disorder (AUD) is one of the top behavioral causes of global disease burden in the United States. Repeated cycles of alcohol intoxication and abstinence induce neuroplastic alterations which induce excessive drinking and cognitive impairments. A system deeply dysregulated by chronic drinking is norepinephrine (NE). At moderate levels, NE has beneficial effects on cognition and behavior, mediated by the α2 adrenergic receptor (AR) subtype. Whether α2 AR activation blunts alcohol consumption in models of heavy drinking has not been determined, and whether α2 AR activation improves cognitive performance following chronic alcohol is unknown. Here, we show that the α2 AR agonist clonidine worsens ethanol-induced hypothermia and sedation in male mice, while the more selective α2 AR agonist guanfacine is devoid of these effects. We also observed that, in male and female mice, while both clonidine and guanfacine reduce heavy alcohol drinking, guanfacine does so with higher potency. Furthermore, guanfacine improved cognitive performance in a temporal order test and, partially, in a novel object recognition test, but had no effect in a novel spatial location test, in male and female ethanol experienced mice. Finally, we found that chronic intermittent ethanol drinking increases the number of persistently activated NE neurons in both the locus coeruleus and the nucleus of the tractus solitarius, in both male and female mice. Our results highlight a central role for the α2 AR system in heavy alcohol drinking and associated cognitive deficits, suggesting that α2 AR stimulation may represent a viable pharmacological strategy to treat AUD.Significance Statement Our data show a major role for the norepinephrine system and the α2 adrenergic receptor subtype in regulating ethanol consumption and improving cognition, and provide support for the use of guanfacine in the management of AUD.