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 utilized chemogenetic tools and viral monosynaptic circuit tracing to analyze these connections and to examine oligodendrocyte progenitor cells (OPC) 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 n...

Depression is a frequent and serious illness and stress is considered the main risk factor for its onset. First-line antidepressants increase serotonin (5-hydroxytryptamine and 5-HT) levels in the brain. We previously reported that an N -acetyltransferase, Shati/Nat8l, is upregulated in the dorsal striatum (dSTR) of stress-susceptible mice exposed to repeated social defeat stress (RSDS) and that dSTR Shati/Nat8l overexpression in mice (dSTR-Shati OE) induces stress vulnerability and local reduction in 5-HT content. Male mice were used in this study, and we found that dSTR 5-HT content decreased in stress-susceptible but not in resilient mice. Moreover, vulnerability to stress in dSTR-Shati OE mice was suppressed by the activation of serotonergic neurons projecting from the dorsal raphe nucleus (dRN) to the dSTR, followed by upregulation of 5-HT content in the dSTR using designer receptors exclusively activated by designer drugs (DREADD). We evaluated the role of GABA in modulating the serotonergic system i...

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys ( Macaca fuscata ): the primary and secondary visual cortices and the inferotemporal cortex. We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimuli through a s...

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 brain is an organ that functions as a network of many elements connected in a nonuniform manner. In the brain, the neocortex is evolutionarily newest and is thought to be primarily responsible for the high intelligence of mammals. In the mature mammalian brain, all cortical regions are expected to have some degree of homology, but have some variations of local circuits to achieve specific functions performed by individual regions. However, few cellular-level studies have examined how the networks within different cortical regions differ. This study aimed to find rules for systematic changes of connectivity (microconnectomes) across 16 different cortical region groups. We also observed unknown trends in basic parameters in vitro such as firing rate and layer thickness across brain regions. Results revealed that the frontal group shows unique characteristics such as dense active neurons, thick cortex, and strong connections with deeper layers. This suggests the frontal side of the cortex is inherently ca...

Respiratory sinus arrhythmia (RSA), the natural variation in heart rate synchronized with respiration, has been extensively studied in emotional and cognitive contexts. Various time or frequency-based methods using the cardiac signal have been proposed to analyze RSA. In this study, we present a novel approach that combines respiratory phase and heart rate to enable a more detailed analysis of RSA and its dynamics throughout the respiratory cycle. To facilitate the application of this method, we have implemented it in an open-source Python toolbox called physio. This toolbox includes essential functionalities for processing electrocardiogram (ECG) and respiratory signals, while also introducing this new approach for RSA analysis. Inspired by previous research conducted by our group, this method enables a cycle-by-cycle analysis of RSA providing the possibility to correlate any respiratory feature to any RSA feature. By employing this approach, we aim to gain a more accurate understanding of the neural mech...

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 ...

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys ( Macaca fuscata ): the primary and secondary visual cortices (V1, V2) and the inferotemporal cortex (IT). We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimu...