The Drosophila mushroom body (MB) is an important model system for studying the synaptic mechanisms of associative learning. In this system, coincidence of odor-evoked calcium influx and dopaminergic input in the presynaptic terminals of Kenyon cells (KCs), the principal neurons of the MB, triggers long-term depression (LTD), which plays a critical role in olfactory learning. However, it is controversial whether such synaptic plasticity is accompanied by a corresponding decrease in odor-evoked calcium activity in the KC presynaptic terminals. Here, we address this question by inducing LTD by pairing odor presentation with optogenetic activation of dopaminergic neurons (DANs). This allows us to rigorously compare the changes at the presynaptic and postsynaptic sites in the same conditions. By imaging presynaptic acetylcholine release in the condition where LTD is reliably observed in the postsynaptic calcium signals, we show that neurotransmitter release from KCs is depressed selectively in the MB compartme...

Intracranial electroencephalography (iEEG) provides a unique opportunity to record and stimulate neuronal populations in the human brain. A key step in neuroscience inference from iEEG is localizing the electrodes relative to individual subject anatomy and identified regions in brain atlases. We describe a new software tool, Your Advanced Electrode Localizer (YAEL), that provides an integrated solution for every step of the electrode localization process. YAEL is compatible with all common data formats to provide an easy-to-use, drop-in replacement for problematic existing workflows that require users to grapple with multiple programs and interfaces. YAEL's automatic extrapolation and interpolation functions speed localization, especially important in patients with many implanted stereotactic (sEEG) electrode shafts. The graphical user interface is presented in a web browser for broad compatibility and includes an interactive 3D viewer for easier localization of nearby sEEG contacts. After localization is ...

Traumatic brain injury (TBI) affects millions of people annually and is a leading cause of long-term disability. Individuals with this condition commonly manifest behavioral, psychiatric, and cognitive dysfunctions, yet there is inadequate understanding of underlying mechanisms, posing challenges for effective treatments. TBI often arises from physical trauma to the head resulting in focal or diffuse injury, long-term cell loss, and tissue damage depending on injury type. Focal injuries can be modeled with the controlled cortical impact (CCI), while fluid percussion injury (FPI) models diffuse concussive injuries. Furthermore, each type of injury can be further classified based on severity (e.g., mild, moderate, and severe), each with their own unique pathophysiology. In mild TBI, diffuse injury leads to cell loss, diffuse axonal injury, and related circuit alterations in both afferent and efferent networks connecting to the injured cortical area (Krishna et al., 2020). It is recognized that dysfunction of...

In the article “Time Course of Alterations in Adult Spinal Motoneuron Properties in the SOD1(G93A) Mouse Model of ALS,” by Seoan Huh, Charles J. Heckman, and Marin Manuel, which was published online on February 25, 2021, Figure 8 appeared incorrectly. A sign error occurred when calculating the effect …

Functional neural circuits in the cerebral cortex are established through specific neural connections between excitatory and various inhibitory cell types. However, the molecular mechanisms underlying synaptic partner recognition remain unclear. In this study, we examined the impact of clustered protocadherin-γ ( cPcdhγ ) gene deletion in parvalbumin-positive (PV+) cells on intralaminar and translaminar neural circuits formed between PV+ and pyramidal (Pyr) cells in the primary visual cortex (V1) of male and female mice. First, we used whole-cell recordings and laser-scan photostimulation with caged glutamate to map excitatory inputs from layer 2/3 to layer 6. We found that cPcdhγ -deficient PV+ cells in layer 2/3 received normal translaminar inputs from Pyr cells through layers 2/3–6. Second, to further elucidate the effect on PV+-Pyr microcircuits within intralaminar layer 2/3, we conducted multiple whole-cell recordings. While the overall connection probability of PV+-Pyr cells remained largely unchange...

The levels of purines, essential molecules to sustain eukaryotic cell homeostasis, are regulated by the coordination of the de novo and salvage synthesis pathways. In the embryonic central nervous system (CNS), the de novo pathway is considered crucial to meet the requirements for the active proliferation of neural stem/progenitor cells (NSPCs). However, how these two pathways are balanced or separately used during CNS development remains poorly understood. In this study, we showed a dynamic shift in pathway utilization, with greater reliance on the de novo pathway during embryonic stages and on the salvage pathway in postnatal–adult mouse brain. The pharmacological effects of various purine synthesis inhibitors in vitro and the expression profile of purine synthesis enzymes indicated that NSPCs in the embryonic cerebrum mainly use the de novo pathway. Simultaneously, NSPCs in the cerebellum require both the de novo and the salvage pathways. In vivo administration of de novo inhibitors resulted in severe h...

Cajal–Retzius (CR) cells are transient neurons with long-lasting effects on the architecture and circuitry of the neocortex and hippocampus. Contrary to the prevailing assumption that CR cells completely disappear in rodents shortly after birth, a substantial portion of these cells persist in the hippocampus throughout adulthood. The role of these surviving CR cells in the adult hippocampus is largely unknown, partly because of the paucity of suitable tools to dissect their functions in the adult versus the embryonic brain. Here, we show that genetic crosses of the Δ Np73-Cre mouse line, widely used to target CR cells, to reporter mice induce reporter expression not only in CR cells, but also progressively in postnatal dentate gyrus granule neurons. Such a lack of specificity may confound studies of CR cell function in the adult hippocampus. To overcome this, we devise a method that not only leverages the temporary CR cell-targeting specificity of the Δ Np73-Cre mice before the first postnatal week, but al...

Similar to a camera aperture, pupil size adjusts to the surrounding luminance. Unlike a camera, pupil size is additionally modulated both by stimulus properties and by cognitive processes, including attention and arousal, though the interdependence of these factors is unclear. We hypothesized that different stimulus properties interact to jointly modulate pupil size while remaining independent from the impact of arousal. We measured pupil responses from human observers to equiluminant stimuli during a demanding rapid serial visual presentation (RSVP) task at fixation and tested how response amplitude depends on contrast, spatial frequency, and reward level. We found that under constant luminance, unattended stimuli evoke responses that are separable from changes caused by general arousal or attention. We further uncovered a double-dissociation between task-related responses and stimulus-evoked responses, suggesting that different sources of pupil size modulation are independent of one another. Our results ...

The auditory system relies on both local and summary representations; acoustic local features exceeding system constraints are compacted into a set of summary statistics. Such compression is pivotal for sound-object recognition. Here, we assessed whether computations subtending local and statistical representations of sounds could be distinguished at the neural level. A computational auditory model was employed to extract auditory statistics from natural sound textures (i.e., fire, rain) and to generate synthetic exemplars where local and statistical properties were controlled. Twenty-four human participants were passively exposed to auditory streams while the electroencephalography (EEG) was recorded. Each stream could consist of short, medium, or long sounds to vary the amount of acoustic information. Short and long sounds were expected to engage local or summary statistics representations, respectively. Data revealed a clear dissociation. Compared with summary-based ones, auditory-evoked responses based...

The timing and specificity of oligodendrocyte myelination during development, as well as remyelination after injury or immune attack, remain poorly understood. Recent work has shown that oligodendrocyte progenitors receive synapses from neurons, providing a potential mechanism for neuronal-glial communication. In this study, we investigated the importance of these neuroglial connections in myelination during development and during neuronal plasticity in the mouse hippocampus. We used chemogenetic tools and viral monosynaptic circuit tracing to analyze these connections and to examine oligodendrocyte progenitor cells (OPCs) proliferation, myelination, synapse formation, and neuronal-glial connectivity in vivo after increasing or decreasing neuronal activity levels . We found that increasing neuronal activity led to greater OPC activation and proliferation. Modulation of neuronal activity also altered the organization of neuronal-glial connections: while it did not impact the total number of RabV-labeled neu...