The detection of a single photon by a rod photoreceptor is limited by two sources of physiological noise, called discrete and continuous noise. Discrete noise occurs as intermittent current deflections with a waveform very similar to that of the single-photon response to real light and is thought to be produced by spontaneous activation of rhodopsin. Continuous noise occurs as random and continuous fluctuations in outer-segment current and is usually attributed to some intermediate in the phototransduction cascade. To confirm the origin of these noise sources, we have recorded from retinas of mouse lines with rods having reduced levels of rhodopsin, transducin or phosphodiesterase. We show that the rate of discrete noise is diminished in proportion to the decrease in rhodopsin concentration, and that continuous noise is independent of transducin concentration but clearly elevated when the level of phosphodiesterase is reduced. Our experiments provide new molecular evidence that discrete noise is indeed pro...

Spatial memories are represented by hippocampal place cells during navigation. This spatial code is dynamic, undergoing changes across time – known as representational drift – and across changes in internal state, even while navigating the same spatial environment with consistent behavior. A dynamic code may provide the hippocampus a means to track distinct epochs of experience that occur at different times or during different internal states and update spatial memories. Changes to the spatial code include place fields that remap to new locations and place fields that vanish, while others are stable. However, what determines place field fate across epochs remains unclear. We measured the lap-by-lap properties of place cells in mice during navigation for a block of trials in a rewarded virtual environment. We then determined the position of the place fields in another block of trials in the same spatial environment either separated by a day (a distinct temporal epoch) or during the same session but with rew...

Due to the legalization of Cannabis in many jurisdictions and trend of increasing THC content in Cannabis products, an urgent need exists to understand the impact of Cannabis use during pregnancy on fetal neurodevelopment and behavior. To this end, we exposed female Sprague-Dawley rats to Cannabis smoke daily from gestational days 6 to 20 or room-air. Maternal reproductive parameters, offspring behavior, and gene expression in the offspring amygdala were assessed. Body temperature was decreased in dams following smoke exposure and more fecal boli were observed in the chambers before and after smoke exposure in dams exposed to smoke. Maternal weight gain, food intake, gestational length, litter number, and litter weight were not altered by exposure to Cannabis smoke. A significant increase in the male-to-female ratio was noted in the Cannabis -exposed litters. In adulthood, male and female Cannabis smoke-exposed offspring explored the inner zone of an open field significantly less than control offspring. Ge...

Serotonergic neurons in the rostral ventral medulla (RVM) contribute to bidirectional control of pain through modulation of spinal and trigeminal nociceptive networks. Deficits in this pathway are believed to contribute to pathological pain states, but whether changes in serotonergic mechanisms are pro or anti-nociceptive is debated. We used a combination of optogenetics and fiber photometry to examine these mechanisms more closely. We find that optogenetic activation of RVM serotonergic afferents in the spinal cord of naïve mice produces mechanical hypersensitivity and conditioned place aversion. Neuropathic pain, produced by chronic constriction injury of the infraorbital nerve (CCI-ION), evoked a tonic increase in serotonin concentrations within the spinal trigeminal nucleus caudalis (SpVc), measured with liquid chromatography-tandem mass spectroscopy (LC-MS/MS). By contract, CCI-ION had no effect on the phasic serotonin transients in SpVc, evoked by noxious pinch, and measured with fiber photometry of ...

Antibody-based imaging techniques rely on reagents whose performance may be application-specific. Because commercial antibodies are validated for only a few purposes, users interested in other applications may have to perform extensive in-house antibody testing. Here we present a novel application-specific proxy screening step to efficiently identify candidate antibodies for array tomography (AT), a serial section volume microscopy technique for high-dimensional quantitative analysis of the cellular proteome. To identify antibodies suitable for AT-based analysis of synapses in mammalian brain, we introduce a heterologous cell-based assay that simulates characteristic features of AT, such as chemical fixation and resin embedding that are likely to influence antibody binding. The assay was included into an initial screening strategy to generate monoclonal antibodies that can be used for AT. This approach simplifies the screening of candidate antibodies and has high predictive value for identifying antibodies...

Psychotic drugs such as ketamine induce symptoms close to schizophrenia, and stimulate the production of gamma oscillations, as also seen in patients, but the underlying mechanisms are still unclear. Here, we have used computational models of cortical networks generating gamma oscillations, and have integrated the action of drugs such as ketamine to partially block n-methyl-d-Aspartate (NMDA) receptors. The model can reproduce the paradoxical increase of gamma oscillations by NMDA-receptor antagonists, assuming that antagonists affect NMDA receptors with higher affinity on inhibitory interneurons. We next used the model to compare the responsiveness of the network to external stimuli, and found that when NMDA channnels are blocked, an increase of gamma power is observed altogether with an increase of network responsiveness. However, this responsiveness increase applies not only to gamma states, but also to asynchronous states with no apparent gamma. We conclude that NMDA antagonists induce an increased exc...

Extracting common patterns of neural circuit computations in the autism spectrum and confirming them as a cause of specific core traits of autism is the first step towards identifying cell- and circuit-level targets for effective clinical intervention. Studies in humans with autism have identified functional links and common anatomical substrates between core restricted behavioral repertoire, cognitive rigidity, and over-stability of visual percepts during visual rivalry. To study these processes with single-cell precision and comprehensive neuronal population coverage, we developed the visual bi-stable perception paradigm for mice based on ambiguous moving plaid patterns consisting of two transparent gratings drifting at an angle of 120°. This results in spontaneous reversals of the perception between local component motion (plaid perceived as two separate moving grating components) and integrated global pattern motion (plaid perceived as a fused moving texture). This robust paradigm doesn’t depend on the...

Electro-acupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of EA in neurological repair after SCI. Firstly, we investigated the role of EA in the neurological repair of the SCI rat model. The expression levels of Human antigen R (HuR) and Kruppel-like factor 9 (KLF9) in spinal cord tissues were quantified after EA treatment. Secondly, we carried out bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Lastly, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurological repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA significantly diminished the S...

Migratory locusts enter a reversible hypometabolic coma to survive environmental anoxia, wherein the cessation of central nervous system (CNS) activity is driven by spreading depolarization (SD). While glycolysis is recognized as a crucial anaerobic energy source contributing to animal anoxia tolerance, its influence on the anoxic SD trajectory and recovery outcomes remains poorly understood. We investigated the effects of varying glycolytic capacity on adult female locust anoxic SD parameters, using glucose or the glycolytic inhibitors 2-deoxy-D-glucose (2DG) or monosodium iodoacetate (MIA). Surprisingly, 2DG treatment shared similarities with glucose yet had opposite effects compared to MIA. Specifically, though SD onset was not affected, both glucose and 2DG expedited the recovery of CNS electrical activity during reoxygenation, whereas MIA delayed it. Additionally, glucose and MIA, but not 2DG, increased tissue damage and neural cell death following anoxia-reoxygenation. Notably, glucose-induced injuri...

SQUID-based magnetoencephalography has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited due to several constraints such as cost, fixed helmet size and obligation of immobility. A new generation of sensors, the optically pumped magnetometers (OPMs), could overcome these limitations. In this study, we validate the ability of Helium-based OPM (4He-OPM) sensors to record epileptic brain activity thanks to simultaneous recordings with intracerebral EEG (stereotactic EEG, SEEG). We recorded simultaneous SQUIDs-SEEG and 4He-OPM-SEEG signals in one patient during two sessions. We show that epileptic activities on intracerebral EEG can be recorded by OPMs with a better signal-to noise ratio than classical SQUIDs. The OPM sensors open new venues for the widespread application of magnetoencephalography in the management of epilepsy and other neurological diseases and fundamental neuroscience. Significance Stateme...