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 ΔNp73-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 ΔNp73-Cre mice before the first postnatal week, but also ...

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 utilized 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 utilize 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 ...

Spoken language contains information at a broad range of timescales, from phonetic distinctions on the order of milliseconds to semantic contexts which shift over seconds to minutes. It is not well understood how the brain's speech production systems combine features at these timescales into a coherent vocal output. We investigated the spatial and temporal representations in cerebral cortex of three phonological units with different durations: consonants, vowels, and syllables. Electrocorticography recordings were obtained from five participants while speaking single syllables. We developed a novel clustering and Kalman filter-based trend analysis procedure to sort electrodes into temporal response profiles. A linear discriminant classifier was used to determine how strongly each electrode's response encoded phonological features. We found distinct time-courses of encoding phonological units depending on their duration: consonants were represented more during speech preparation, vowels were represented eve...

The annual Neuroscience meeting yields significant, measurable impacts that conflict with the environmental commitment of the society and IPCC’s recommendations to address the climate emergency (IPCC, 2018). We used 12,761 presenters’ origins, two online carbon calculators, and benchmark values to estimate 2018 meeting-related travel, event venue operations, and hotel accommodation emissions. Presenters’ conference travel resulted in between 17,298 and 8,690 t CO2, with or without radiative forcing index factors. Over 92% of authors traveled by air and were responsible for over 99% of total travel-related emissions. Extrapolations based upon 28,691 registrants yielded between 69,592.60 t CO2e and 38,010.85 t CO2 from travel. Comparatively, authors’ and registrants’ hotel accommodation emissions equaled 429 and 965 t CO2e, whereas operation of the San Diego Convention Center equaled about 107 t CO2e. We relate SfN meeting-related emissions to potential September Arctic sea ice loss, labor productivity loss ...

Hippocampal Inhibitory Neurons (INs) contact local targets and project to different brain areas to form synapses on distal neurons. Despite the importance of INs for hippocampal function and interregional brain communication, the impact of activity-dependent plasticity mechanisms on local and long-range GABAergic synapses formed by hippocampal INs remains to be fully elucidated. Here, we use optogenetic-coupled electrophysiology in mice to show that protein kinase A (PKA), a master regulator of GABAergic synapse plasticity, causes a form of long-term potentiation of inhibitory synapses (iLTP) in hippocampal granule cells (GCs). This form of iLTP is observed in GCs synapses originated in local INs expressing the marker somatostatin (SST) but not in those expressing parvalbumin (PV). Long-range synapses formed by SST INs onto medial septum neurons are unaffected by PKA activation. iLTP of local SST synapses on GCs is accompanied by changes in presynaptic probability of release and is occluded by pharmacologi...

Dopamine receptor type 2-expressing medium spiny neurons (D2-MSNs) in the medial part of the ventral striatum (VS) induce non-REM (NREM) sleep from the wake state in animals. However, it is unclear whether D2-MSNs in the lateral part of the VS (VLS), which is anatomically and functionally different from the medial part of the VS, contribute to sleep-wake regulation. This study aims to clarify whether and how D2-MSNs in the VLS are involved in sleep-wake regulation. Our study found that specifically removing D2-MSNs in the VLS led to an increase in wakefulness time in mice during the dark phase using a diphtheria toxin-mediated cell ablation/dysfunction technique. D2-MSN ablation throughout the VS further increased dark phase wakefulness time. These findings suggest that VLS D2-MSNs may induce sleep during the dark phase with the medial part of the VS. Next, our fiber photometric recordings revealed that the population intracellular calcium (Ca2+) signal in the VLS D2-MSNs increased during the transition fr...

Neuronal cell body analysis is crucial for quantifying changes in neuronal sizes under different physiological and pathological conditions. Neuronal cell body detection and segmentation mainly rely on manual or pseudo-manual annotations. Manual annotation of neuronal boundaries is time-consuming, requires human expertise, and has intra-/inter observer variances. Also, determining where the neuron’s cell body ends and where the axons and dendrites begin is taxing. We developed a deep-learning-based approach that uses a state-of-the-art shifted windows (Swin) transformer for automated, reproducible, fast, and unbiased 2D detection and segmentation of neuronal somas imaged in mouse acute brain slices by multiphoton microscopy. We tested our Swin algorithm during different experimental conditions of low and high signal fluorescence. Our algorithm achieved a mean Dice score of 0.91, a precision of 0.83, and a recall of 0.86. Compared to two different convolutional neural networks, the Swin transformer outperfor...

The sucrose preference test (SPT) is a widely used preclinical assay for studying stress-sensitive reward behaviors and antidepressant treatments in rodents, with some face, construct, and predictive validity. However, while stress-induced loss of sucrose preference is presumed to reflect an anhedonic-like state, little detail is known about what behavioral components may influence performance in the SPT in stress-naïve or stressed rodents. We analyzed the licking microstructure of mice during the SPT to evaluate how preference is expressed and lost following chronic stress. In stress-naïve mice, preference is expressed as both longer and more numerous drinking bouts at the sucrose bottle, compared to the water bottle. We also found evidence that memory of the sucrose bottle location supports preference. Through manipulations of the caloric content of the sweetener or caloric need of the mouse, we found that energy demands and satiety signals do not affect either preference or the underlying drinking behav...

Drug-induced taste disorders reduce quality of life, but little is known about the molecular mechanisms by which drugs induce taste disturbances. In this study, we investigated the short- and long-term effects of the antiarrhythmic drug flecainide, which is known to cause taste dysfunction. Analyses of behavioral responses (licking tests) revealed that mice given a single intraperitoneal injection of flecainide exhibited a significant reduction in preference for a sour tastant (HCl) but not for other taste solutions (NaCl, quinine, sucrose, KCl and monopotassium glutamate) when compared with controls. Mice administered a single dose of flecainide also had significantly higher taste nerve responses to HCl but not to other taste solutions. Compared with controls, mice administered flecainide once-daily for 30 days showed a reduced preference for HCl without any changes in the behavioral responses to other taste solutions. The electrophysiological experiments using HEK293T cells transiently expressing otopetr...

In neurophysiology, achieving precise correlation between physiological responses and anatomical structures is a significant challenge. Therefore, the accuracy of the electrode marking method is crucial. In this study, we describe a tungsten-deposition method, in which tungsten oxide is generated by applying biphasic current pulses to conventional tungsten electrodes. The electrical current used was 40–50 µA, which is similar to that used in electrical microstimulation experiments. The size of the markings ranged from 10 µm to 100 µm, corresponding to the size of the electrode tip, which is smaller than that of existing marking methods. Despite the small size of the markings, detection is easy as the marking appears in bright red under dark-field observation after Nissl staining. This marking technique resulted in low tissue damage and was maintained in vivo for at least 2 years. The feasibility of this method was tested in mouse and macaque brains. Significance Statement A new marking method was develo...