Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with urge incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, and an adult mouse model would expand opportunities to explore these mechanisms in preclinical experiments. Here, we describe the first mouse model of chronic, communicating hydrocephalus with normal intracranial pressure. Hydrocephalic male and female mice had unsteady gait and reduced maximum velocity. Despite performing well on a variety of behavioral tests, they exhibited subtle learning impairments. Hydrocephalic mice also developed urinary frequency, and many became incontinent. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore the neural circuit mechanisms of these symptoms. Preclinical work using this hyd...

In the article “Homeostatic Regulation of Spike Rate within Bursts in Two Distinct Preparations,” by Alishah Lakhani, Carlos Gonzalez-Islas, Zahraa Sabra, Nicholas Au …

Brain-derived estrogen (17β-estradiol, E2) is a neuromodulator that plays important roles in neural plasticity and network excitability. Chronic inhibition of estrogen synthesis is used in adjuvant breast cancer therapy for estrogen receptor-positive tumors and may have been associated with cognitive and affective side effects. Here, we have developed a model of adjuvant therapy in female ovariectomized mice in which the E2 biosynthetic enzyme aromatase is inhibited by letrozole (1 mg/kg/day, i.p., for up to 3 weeks), Using two-photon longitudinal in vivo imaging in Thy1-GFP-M mice, we found that spine density in the apical dendrites of neocortical layer 5 pyramidal cells was unaffected by letrozole treatment but spine turnover was reduced. LTP in layer 4 to layer 2/3 synapses in the somatosensory cortex was also reduced in slices from letrozole-treated mice, showing deficits in structural and functional plasticity resulting from aromatase inhibition. Ovariectomized mice performed worse than intact control...

Social status and dominance are critical factors influencing well-being and survival across multiple species. However, dominance behaviors vary widely across species, from elaborate feather displays in birds to aggression in chimps. To effectively study dominance, it is essential to clearly define and reliably measure dominance behaviors. In laboratory settings, C57BL/6 mice are commonly used to study dominance due to their stable and linear social hierarchies. However, other mouse strains are also used for laboratory research. Despite substantial evidence for strain effects on behavioral repertoires, the impact of strain on dominance in mice remains largely unstudied. To address this gap, we compared dominance behaviors between CD1 and C57BL/6 male mice across four assays: observation of agonistic behaviors, urine marking, tube test, and a reward competition. We found that CD1 mice demonstrate increased fighting, increased territorial marking through urination, and increased pushing and resisting in the t...

Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM; this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 ( N  = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of nontarget responses (a.k.a. failure of feature binding, p NT). In Experiment 2 ( N  = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to misbinding (i.e., participants self-reported “remembered” in nontarget responses) or informed guessing trials (participants self...

Here we test the stochastic dynamic operator (SDO) as a new framework for describing physiological signal dynamics relative to spiking or stimulus events. The SDO is a natural extension of existing spike-triggered average (STA) or stimulus-triggered average techniques currently used in neural analysis. It extends the classic STA to cover state-dependent and probabilistic responses where STA may fail. In simulated data, SDO methods were more sensitive and specific than the STA for identifying state-dependent relationships. We have tested SDO analysis for interactions between electrophysiological recordings of spinal interneurons, single motor units, and aggregate muscle electromyograms (EMG) of major muscles in the spinal frog hindlimb. When predicting target signal behavior relative to spiking events, the SDO framework outperformed or matched classical spike-triggered averaging methods. SDO analysis permits more complicated spike–signal relationships to be captured, analyzed, and interpreted visually and i...

Successful behavior depends on the attentional state and other factors related to decision-making, which may modulate neuronal activity differently. Here, we investigated whether attentional state and behavioral outcome (i.e., whether a target is detected or missed) are distinguishable using the power and phase of local field potential recorded bilaterally from area V4 of two male rhesus monkeys performing a cued visual attention task. To link each trial's outcome to pairwise measures of attention that are typically averaged across trials, we used several methods to obtain single-trial estimates of spike count correlation and phase consistency. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase in attentional/behavioral discriminability, although single-trial gamma phase consistency provided reasonably high attentional discrimi...

The cortico-basal ganglia loop has traditionally been conceptualized as consisting of three distinct information networks: motor, limbic, and associative. However, this three-loop concept is insufficient to comprehensively explain the diverse functions of the cortico-basal ganglia system, as emerging evidence suggests its involvement in sensory processing, including the auditory systems. In the present study, we demonstrate the auditory cortico-basal ganglia loop by using transgenic mice and viral-assisted labelings. The caudal part of the external globus pallidus (GPe) emerged as a major output nucleus of the auditory cortico-basal ganglia loop with the cortico-striato-pallidal projections as its input pathway and pallido-cortical and pallido–thalamo–cortical projections as its output pathway. GABAergic neurons in the caudal GPe dominantly innervated the nonlemniscal auditory pathway. They also projected to various regions, including the substantia nigra pars lateralis, cuneiform nucleus, and periaqueduct...

The growing field of social neuroscience is reliant on the development of robust, ecologically valid paradigms for simulating social interaction and measuring social cognition in highly controlled laboratory settings. Perspective taking is a key component of social cognition, and accordingly several paradigms aimed at measuring perspective taking exist. A relatively novel paradigm is the ball detection task, in which participants and a virtual agent form independent beliefs about the presence of a target stimulus behind an occluder. Previous studies have shown that incongruent trials (in which the participant's and the agent's beliefs differ) affect participant reaction times and elicit increased neural activity in the so-called mentalizing network. This paradigm has important advantages over previous ones, in that experimental conditions can be fully randomized, and ceiling effects are not found even for adult populations. Here, we combined this paradigm with a stress induction and a nonstressful control ...

Each olfactory cortical hemisphere receives ipsilateral odor information directly from the olfactory bulb and contralateral information indirectly from the other cortical hemisphere. Since neural projections to the olfactory cortex (OC) are disordered and nontopographic, spatial information cannot be used to align projections from the two sides like in the visual cortex. Therefore, how bilateral information is integrated in individual cortical neurons is unknown. We have found, in mice, that the odor responses of individual neurons to selective stimulation of each of the two nostrils are significantly correlated, such that odor identity decoding optimized with information arriving from one nostril transfers very well to the other side. Nevertheless, these aligned responses are asymmetric enough to allow decoding of stimulus laterality. Computational analysis shows that such matched odor tuning is incompatible with purely random connections but is explained readily by Hebbian plasticity structuring bilatera...