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 dopam...

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 si...

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][1]). While the etiology of these disorders is incompletely understood, recent data implicate a role for mitochondrial dysfunction ( [Norkett et al., 2017][2]; [Khaliulin et al., 2025][3]). 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][4]). Mitochondrial Rho-GTPase 1 ( Miro1 ) resides on the outer mitochondrial membrane and facilitates microtubule-mediated mitochondrial motility ( [Fransson et al., 2003][5]). 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., 20...

The life cycle of the model nematode Caenorhabditis elegans involves a choice between two alternative developmental trajectories. Hermaphroditic larvae can either become reproductive adults or, under conditions of crowding or low food availability, enter a long-term, stress-resistant diapause known as the dauer stage. Chemical signals from a secreted larval pheromone promote the dauer trajectory in a concentration-dependent manner, and their influence can be antagonized by increased availability of a microbial food source. The decision is known to be under neuronal control, involving both sensory and interneurons. However, little is known about the dynamics of the underlying circuit, and the circuit mechanisms by which short-term fluctuations in the ratio of food and pheromone experienced by individual larvae are remembered and averaged over several hours. To investigate this, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA ne...

Sulf1 is an extracellular sulfatase that regulates cell signaling by removing 6- O -sulfates from heparan sulfate. Although the roles of Sulf1 in neural development have been studied extensively, its functions in the adult brain remain largely unknown. Here, we report the effects of Sulf1 disruption on the neuronal properties of the medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell, one of the regions highly expressing Sulf1 . We separately labeled MSNs expressing dopamine D1 receptors (D1-MSNs) or D2 receptors (D2-MSNs) by injecting adult male Drd1-Cre and Drd2-Cre mice with a Cre-dependent AAV vector expressing a red fluorescent protein, mCherry, and examined their electrophysiological properties by means of whole-cell patch–clamp recording. In the D2-MSNs, Sulf1 disruption led to drastic changes in neural firing responses to depolarizing current injections: in the Sulf1 knock-out mice, the rheobase was smaller than in the wild-type mice, but the number of action potentials elicited by dep...

We studied the role of movement and outcome information in forming metacognitive representations of agency. Human participants ( N  = 40; 25 female, 15 male, 0 diverse) completed a goal-oriented task: a semivirtual version of a ball-throwing game. In two conditions, we manipulated either the visual representation of the throwing movement or its proximal outcome (the resulting ball trajectory). We measured participants’ accuracy in a discrimination agency task, as well as confidence in their responses and tested for differences in the electrophysiological (EEG) signal using mass linear mixed-effect modeling. We found no mean differences between participants’ metacognitive efficiency between conditions. However, through exploratory analyses, we found that metacognitive sensitivity did not correlate between the two conditions and that the EEG signal differed between the two conditions during the agency discrimination task. We cautiously interpret these results as suggesting that although both movement and out...

Investigations into the neural basis of behavior frequently employ calcium imaging to measure neuronal activity. Across studies, however, seemingly reasonable but highly diverse methodological choices are typically made to assess the selectivity of individual neurons to task states. Here, we examine systematically the effect of parameter choices, along the pipeline from data acquisition through statistical testing, on the inferred encoding preferences of individual neurons. We use, as an experimental testbed, calcium imaging in the medial prefrontal cortex of freely behaving mice engaged in a classic exploration-avoidance task with animal-controlled state transitions, namely, navigation in the elevated zero maze. We report that most of the key parameters in the pipeline substantially impact the inferred selectivity of neurons and do so in distinct ways. Using novel accuracy and robustness metrics, we directly compare the quality of inference across combinations of parameter levels and discover an optimal c...

In a dense-sampling resting–state functional magnetic resonance imaging study, Wang et al. (2025) recorded two individuals’ functional connectivity patterns over 30 consecutive days to find a marker of the passage of time in the human brain. The authors measured the similarity of brain connectivity patterns over days, focusing on key regions involved in spatial navigation and declarative memory that have been previously shown to exhibit slow changes in activity patterns over time: the entorhinal cortex (EC) and the hippocampus (HPC). The authors show that connectivity pattern similarity decreased over time—more temporally distant resting-states had more distinct functional connectivity profiles. This result is consistent with the idea that brain activity intrinsically drifts over time (Driscoll et al., 2022). Additionally, the authors observed an anatomical gradient such that the anterior HPC showed stronger temporal drift than the posterior HPC, and the anterolateral EC showed stronger temporal drift than...

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 consumption 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. Furtherm...

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 backg...