Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its effects on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone (CORT) in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using postmortem histologic evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Normal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in CORT relative to the control group. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may o...

Vision loss from diseases of the outer retina, such as age-related macular degeneration, is among the leading causes of irreversible blindness in the world today. The goal of retinal prosthetics is to replace the photo-sensing function of photoreceptors lost in these diseases with optoelectronic hardware to electrically stimulate patterns of retinal activity corresponding to vision. To enable high-resolution retinal prosthetics, the scale of stimulating electrodes must be significantly decreased from current designs; however, this reduces the amount of stimulating current that can be delivered. The efficacy of subretinal stimulation at electrode sizes suitable for high visual acuity retinal prosthesis are not well understood, particularly within the safe charge injection limits of electrode materials. Here, we measure retinal ganglion cell (RGC) responses in a mouse model of blindness to evaluate the stimulation efficacy of 10, 20, and 30 μm diameter iridium oxide electrodes within the electrode charge inj...

Hyperglycemia is a comorbidity in 60–80% of stroke patients; nevertheless, neuroprotective drugs like NMDA receptor (NMDAR) antagonists are typically assessed in normoglycemic animals at the preclinical stage before they are approved to enter clinical trials. Interestingly, as a possible explanation for the translational failure of NMDAR antagonists, it was recently reported that stroke occurring during nighttime causes smaller infarctions in rodents and therefore has a smaller window for neuroprotection. To investigate why stroke occurring during different circadian phases confers a difference in severity, we reanalyzed the published source data and found that some mice that were used in the daytime have higher blood glucose than mice that were used in the nighttime. We then repeated the experiments but found no difference in blood glucose concentration or infarct volume regardless of the circadian phase during which stroke occurs. On the other hand, induction of hyperglycemia by glucose injection reprodu...

Inflammatory cells including macrophages and microglia synthesize and release the oxysterol, 25-hydroxycholesterol (25HC), which has antiviral and immunomodulatory properties. Here, we examined the effects of lipopolysaccharide (LPS), an activator of innate immunity, on 25HC production in microglia, and the effects of LPS and 25HC on CA1 hippocampal synaptic plasticity and learning. In primary microglia, LPS markedly increases expression of cholesterol 25-hydroxylase (Ch25h), the key enzyme involved in 25HC synthesis, and increases the levels of secreted 25HC. Wild type microglia produced higher levels of 25HC than Ch25h knockout (KO) microglial with or without LPS. LPS treatment also disrupts long-term potentiation (LTP) in hippocampal slices via induction of a form of NMDA receptor-dependent metaplasticity. The inhibitory effects of LPS on LTP were mimicked by exogenous 25HC, and were not observed in slices from Ch25h KO mice. In vivo, LPS treatment also disrupts LTP and inhibits one-trial learning in wi...

Internal affective states produce external manifestations such as facial expressions. In humans, the Facial Action Coding System (FACS) is widely used to objectively quantify the elemental facial action units (AUs) that build complex facial expressions. A similar system has been developed for macaque monkeys—the Macaque FACS (MaqFACS); yet, unlike the human counterpart, which is already partially replaced by automatic algorithms, this system still requires labor-intensive coding. Here, we developed and implemented the first prototype for automatic MaqFACS coding. We applied the approach to the analysis of behavioral and neural data recorded from freely interacting macaque monkeys. The method achieved high performance in the recognition of six dominant AUs, generalizing between conspecific individuals ( Macaca mulatta ) and even between species ( Macaca fascicularis ). The study lays the foundation for fully automated detection of facial expressions in animals, which is crucial for investigating the neural ...

Many receptive fields in the early visual system show standard (center-surround) structure and can be analyzed using simple drifting patterns and a difference-of-Gaussians (DoG) model, which treats the receptive field as a linear filter of the visual image. But many other receptive fields show nonlinear properties such as selectivity for direction of movement. Such receptive fields are typically studied using discrete stimuli (moving or flashed bars and edges) and are modelled according to the features of the visual image to which they are most sensitive. Here, we harness recent advances in tomographic image analysis to characterize rapidly and simultaneously both the linear and nonlinear components of visual receptive fields. Spiking and intracellular voltage potential responses to briefly flashed bars are analyzed using non-negative matrix factorization (NNMF) and iterative reconstruction tomography (IRT). The method yields high-resolution receptive field maps of individual neurons and neuron ensembles i...

Temporal lobe epilepsy remains a common disorder with no cure and inadequate treatments, potentially because of an incomplete understanding of how seizures start. CA1 pyramidal cells and many inhibitory interneurons increase their firing rate in the seconds-minutes before a spontaneous seizure in epileptic rats. However, some interneurons fail to do so, including those identified as putative interneurons with somata in oriens and axons targeting lacunosum-moleculare (OLM cells). Somatostatin-containing cells, including OLM cells, are the primary target of inhibitory vasoactive intestinal polypeptide and calretinin-expressing (VIP/CR) bipolar interneuron-selective interneurons, type 3 (ISI-3). The objective of this study was to test the hypothesis that in epilepsy inhibition of OLM cells by ISI-3 is abnormally increased, potentially explaining the failure of OLM recruitment when needed most during the ramp up of activity preceding a seizure. Stereological quantification of VIP/CR cells in a model of tempora...

Sensory environments are commonly characterized by specific physical features, which sensory systems might exploit using dedicated processing mechanisms. In the tactile sense, one such characteristic feature is frictional movement, which gives rise to short-lasting (<10 ms), information-carrying integument vibrations. Rather than generic integrative encoding (i.e., averaging or spectral analysis capturing the “intensity” and “best frequency”), the tactile system might benefit from, what we call a “temporally local” coding scheme that instantaneously detects and analyzes shapes of these short-lasting features. Here, by employing analytic psychophysical measurements, we tested whether the prerequisite of temporally local coding exists in the human tactile system. We employed pulsatile skin indentations at the fingertip that allowed us to trade manipulation of local pulse shape against changes in global intensity and frequency, achieved by adding pulses of the same shape. We found that manipulation of local p...

Whole slide scanning technology has enabled the generation of high-resolution images from complete tissue sections. However, commonly used analysis software is often unable to handle the large data files produced. Here, we present a method using the open-source software QuPath to detect, classify and quantify fluorescently-labeled cells (microglia and pericytes) in whole coronal brain tissue sections. Whole-brain sections from both male and female NG2DsRed x CX3CR1+/GFP mice were analyzed. Small regions of interest were selected and manual counts were compared with counts generated from an automated approach, across a range of detection parameters. The optimal parameters for detecting cells and classifying them as microglia or pericytes in each brain region were determined and applied to annotations corresponding to the entire somatosensory and motor cortices, hippocampus, thalamus, and hypothalamus in each section. 3.74% of all detected cells were classified as pericytes; however, this proportion was sign...

γ Band plays a key role in the encoding of visual features in the primary visual cortex (V1). In rodents V1 two ranges within the γ band are sensitive to contrast: a broad γ band (BB) increasing with contrast, and a narrow γ band (NB), peaking at ∼60 Hz, decreasing with contrast. The functional roles of the two bands and the neural circuits originating them are not completely clear yet. Here, we show, combining experimental and simulated data, that in mice V1 (1) BB carries information about high contrast and NB about low contrast; (2) BB modulation depends on excitatory-inhibitory interplay in the cortex, while NB modulation is because of entrainment to the thalamic drive. In awake mice presented with alternating gratings, NB power progressively decreased from low to intermediate levels of contrast where it reached a plateau. Conversely, BB power was constant across low levels of contrast, but it progressively increased from intermediate to high levels of contrast. Furthermore, BB response was stronger im...