eNeuro最新文献

The growing therapeutic promise of repeated, low-dose ketamine treatment across various psychopathologies-including depression and drug addiction-warrants clarity on its potential addictive properties and their associated mechanisms in both sexes. Accordingly, the present work examined the effects of intermittent low-dose ketamine in male and female rats on behavioral sensitization to the locomotor-activating effects of ketamine, as well as associated molecular profiles in dopamine D1- and D2-receptor-expressing medium spiny neurons (D1- and D2-MSNs) of the nucleus accumbens (NAc). Following intra-NAc infusion of a Cre-inducible RiboTag virus, locomotor activity was measured in adult Drd1a-iCre and Drd2-iCre male and female rats in either diestrus or proestrus following repeated administration of ketamine (0, 10, or 20 mg/kg, i.p.) to evaluate the development of locomotor sensitization. Female-but not male-rats developed sensitization to the locomotor-activating effects of ketamine, occurring more rapidly in proestrus than in diestrus females at the lower dose tested. To examine enduring context- and cell-type-specific changes in translating mRNAs associated with sensitization to ketamine, RNA sequencing was performed on polyribosome-bound mRNA of D1- and D2-MSNs isolated from the NAc of sensitized females in a drug-free state. A greater number of differentially expressed genes were observed selectively in D1-MSNs of ketamine-treated proestrus versus diestrus females, which were broadly related to regulation of transcription and epitranscriptional modification. These findings provide novel evidence of cell-type-specific and estrous cycle-dependent molecular profiles responsive to intermittent ketamine treatment in female rats and identify posttranscriptional mechanisms with relevance to ketamine's effects on behavioral plasticity.

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.

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.

Alpha peak frequency (APF) is defined as a prominent spectral peak within the 8-12 Hz frequency range. Typically, an individual's alpha frequency is regarded as a stable neurophysiological marker. A wealth of recent evidence, however, indicates that APF shifts within short timescales in relation to task demands and even spontaneously so. Further, brain stimulation studies often report shifts in APF both within and between experimental sessions, directly contradicting the idea of a stable APF. To characterize the nonstationarities in spectral parameters, we estimated APFs from 1 s epochs of resting-state magnetoencephalography (MEG) recordings from healthy adults of either sex. To enhance signal-to-noise ratio, without compromising on temporal resolution, we averaged power spectra within parcelled regions. Our findings indicate that variation in APFs exacerbates along the posterior-to-anterior cortical plane, i.e., from the occipital to the frontal cortices. Further, by comparisons with amplitude-matched simulated signals, we demonstrated that the observed gradient is not attributable to measurement noise. Across the cortex, APFs showed poor temporal reliability, raising the question of whether APFs are more like a transient state than a trait. In general, our study elucidates the dynamic characteristics of alpha oscillations and reveals systematic regional differences which are, in part, shaped by underlying signal-to-noise ratio inherent to MEG recordings.