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 ...

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...

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 co...

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—a...

Picture a man in a deckchair, umbrella overhead, relaxing with a drink in hand—while surrounded by industrial wasteland and decay. This was the iconic 1975 album cover for Supertramp's Crisis? What Crisis? The image perfectly captured the cognitive dissonance of denying catastrophe while sitting in its midst. Rick Davies conceived the artwork to satirize how some responded to England's economic crisis of the mid-1970s: “Crisis? What crisis?” Fifty years later, I find myself in my own version of that deckchair—though instead of industrial ruins, I am surrounded by what may be “arguably the largest science crisis of all time.” And just like that man with his parasol, I am tempted to pretend everything is fine (Figure 1). But it is not fine. Not even close. We are facing an uncomfortable truth: the scientific literature is being flooded with fraudulent papers on an industrial scale. This crisis threatens to erode public trust in research at the very moment we need that trust most. Paper mills are commercia...

In the article, “Emotions in the Brain Are Dynamic and Contextually Dependent: Using Music to Measure Affective Transitions” by Matthew E. Sachs, Mariusz S. Kozak, Kevin N. Ochsner, and …

Episodic timing refers to the one-shot, automatic encoding of temporal information in the brain, in the absence of attention to time. A previous magnetoencephalography (MEG) study showed that the relative burst time of spontaneous alpha oscillations (α) during quiet wakefulness was a selective predictor of retrospective duration estimation. This observation was interpreted as α embodying the “ticks” of an internal contextual clock. Herein, we replicate and extend these findings using electroencephalography (EEG), assess robustness to time-on-task effects, and test the generalizability in virtual reality (VR) environments. In three EEG experiments, 128 participants of either sex underwent 4 min eyes-open resting-state recordings followed by an unexpected retrospective duration estimation task. Experiment 1 tested participants before any tasks, Experiment 2 after 90 min of timing tasks, and Experiment 3 in VR environments of different sizes. We successfully replicated the original MEG findings in Experiment ...

There has been a long-term need for a low-cost, highly efficient, and high-fidelity epilepsy monitoring unit (EMU) suitable for synchronized multimodal home-cage monitoring of small-animal models of epilepsy and spreading depolarization. We present an accessible, scalable, highly space- and energy-efficient EMU capable of fulfilling chronic, continuous, synchronized, multiple-animal monitoring jobs. Each rig within the EMU can provide 16-channel high-fidelity, DC-sensitive biopotential recordings, head acceleration monitoring, voltammetry applications, and synchronized video recording on one freely moving rat. We present the overall EMU architecture design and subsystem details in each recording rig. We demonstrate long-term continuous in vivo recordings of spontaneous seizure and seizure-associated spreading depolarization from freely moving rats (male, 21; female, 6) prepared under the tetanus toxin model of temporal lobe epilepsy.

Perinatal exposure to the organophosphorus insecticide chlorpyrifos (CPF) is associated with an increased incidence of neurodevelopmental disorders, such as autism spectrum disorder. While these behavioral detriments have been modeled in rodents, the underlying functional alterations in the developing brain are largely unknown. Previous reports using a rat model have identified alterations to both inhibitory synaptic transmission and serotonergic (5-HT) receptor binding in the cortex following developmental CPF exposure. Here, we use a rat model of gestational CPF exposure to investigate whether this altered inhibitory activity is driven by increased spontaneous firing of inhibitory interneurons and altered 5-HT receptor expression. Using cell-attached ex vivo electrophysiology in young rats of both sexes, we identified a significant increase in the number of spontaneously firing neurons in the somatosensory cortex of CPF-exposed offspring. Analysis of action potential metrics identified a subset of these ...

Bimanual coordination, fundamental to human motor control, typically involves the execution of different functions by the two limbs (e.g., opening a jar). Previous research has largely investigated bimanual control through simple coordination tasks in which the limbs perform similar movements (e.g., finger tapping); however, few studies have specifically examined coordination when the two limbs perform different yet complementary functions. In the current study, participants performed point-to-point movements of a rectangular cursor, where one limb controlled cursor trajectory and the other rotated a knob to match a target orientation. Participants ( N  = 116, 76 female, 1 nonbinary; 92% right-handed) were divided into four groups and completed the task with a visual feedback gain perturbation (an increase or decrease) applied either to the cursor trajectory or orientation. Our results showed rapid adaptation to perturbations of visual feedback of the movement trajectory, affecting both the perturbed limb ...