The accumulation of amyloid- β ( Aβ ) and hyperphosphorylated-tau (hp-tau) are two classical histopathological biomarkers in Alzheimer’s disease (AD). However, their detailed interactions with the electrophysiological changes at the meso- and macroscale are not yet fully understood. We developed a mechanistic multiscale model of AD progression, linking proteinopathy to its effects on neural activity and vice-versa. We integrated a heterodimer model of prion-like protein propagation and a brain network model of Jansen–Rit neural masses derived from human neuroimaging data whose parameters varied due to neurotoxicity. Results showed that changes in inhibition guided the electrophysiological alterations found in AD, and these changes were mainly attributed to Aβ effects. Additionally, we found a causal disconnection between cellular hyperactivity and interregional hypersynchrony contrary to previous beliefs. Finally, we demonstrated that early Aβ and hp-tau depositions’ location determine the spatiotemporal p...

The inferior colliculus (IC), the midbrain auditory integration center, analyzes information about social vocalizations and provides substrates for higher level processing of vocal signals. We used multichannel recordings to characterize and localize responses to social vocalizations and synthetic stimuli within the IC of female and male mice, both urethane anesthetized and unanesthetized. We compared responses to ultrasonic vocalizations (USVs) with other vocalizations in the mouse repertoire and related vocal responses to frequency tuning, IC subdivisions, and sex. Responses to lower frequency, broadband social vocalizations were widespread in IC, well represented throughout the tonotopic axis, across subdivisions, and in both sexes. Responses to USVs were much more limited. Although we observed some differences in tonal and vocal responses by sex and subdivision, representations of vocal responses by sex and subdivision were largely the same. For most units, responses to vocal signals occurred only when...

This systematic review presented a comprehensive survey of studies that applied transcranial magnetic stimulation and transcranial electrical stimulation to parietal and nonparietal areas to examine the neural basis of symbolic arithmetic processing. All findings were compiled with regard to the three assumptions of the triple-code model (TCM) of number processing. Thirty-seven eligible manuscripts were identified for review (33 with healthy participants and 4 with patients). Their results are broadly consistent with the first assumption of the TCM that intraparietal sulcus both hold a magnitude code and engage in operations requiring numerical manipulations such as subtraction. However, largely heterogeneous results conflicted with the second assumption of the TCM that the left angular gyrus subserves arithmetic fact retrieval, such as the retrieval of rote-learned multiplication results. Support is also limited for the third assumption of the TCM, namely, that the posterior superior parietal lobule engag...

In many real-life scenarios, our decisions could lead to multiple outcomes that conflict with value. Hence, an appropriate neural representation of the net experienced value of conflicting outcomes, which play a crucial role in guiding future decisions, is critical for adaptive behavior. As some recent functional neuroimaging work has primarily focused on the concurrent processing of monetary gains and aversive information, very little is known regarding the integration of conflicting value signals involving monetary losses and appetitive information in the human brain. To address this critical gap, we conducted a functional MRI study involving healthy human male participants to examine the nature of integrating positive emotion and monetary losses. We employed a novel experimental design where the valence (positive or neutral) of an emotional stimulus indicated the type of outcome (loss or no loss) in a choice task. Specifically, we probed two plausible integration patterns while processing conflicting va...

As the global elderly population grows, age-related cognitive decline is becoming an increasingly significant healthcare issue, often leading to various neuropsychiatric disorders. Among the many molecular players involved in memory, AMPA-type glutamate receptors are known to regulate learning and memory, but how their dynamics change with age and affect memory decline is not well understood. Here, we examined the in vivo properties of the AMPA-type glutamate receptor GLR-1 in the AVA interneuron of the Caenorhabditis elegans nervous system during physiological aging. We found that both total and membrane-bound GLR-1 receptor levels decrease with age in wild-type worms, regardless of their location along the axon. Using fluorescence recovery after photobleaching, we also demonstrated that a reduction in GLR-1 abundance correlates with decreased local, synaptic GLR-1 receptor dynamics. Importantly, we found that reduced GLR-1 levels strongly correlate with the age-related decline in short-term associative m...

Long-term programmed rheostatic changes in physiology are essential for animal fitness. Hypothalamic nuclei and the pituitary gland govern key developmental and seasonal transitions in reproduction. The aim of this study was to identify the molecular substrates that are common and unique to developmental and seasonal timing. Adult and juvenile quail were collected from reproductively mature and immature states, and key molecular targets were examined in the mediobasal hypothalamus (MBH) and pituitary gland. qRT-PCR assays established deiodinase type 2 ( DIO2 ) and type 3 ( DIO3 ) expression in adults changed with photoperiod manipulations. However, DIO2 and DIO3 remain constitutively expressed in juveniles. Pituitary gland transcriptome analyses established that 340 transcripts were differentially expressed across seasonal photoperiod programs and 1,189 transcripts displayed age-dependent variation in expression. Prolactin ( PRL ) and follicle-stimulating hormone subunit beta ( FSHβ ) are molecular markers...

Neuroscience research demands focused attention built upon a foundational knowledge that can encompass the full sweep of science and engineering including, among other disciplines, psychology, biology, chemistry, physics, and computer science. Neuroscience studies range from evolution of life-forms to new innovations in computational modeling. Neuroscientists can look at the population-level behavior, activity of the human brain, or atomic-level resolution of essential molecules. And yet, within these depths of emerging knowledge, the neuroscience community has the capacity to share what we know with young people and the public at large. Even little actions of communicating science in a manner that is broadly accessible and fun can initiate that ripple effect that informs a young mind. Television and social media are dominated with advertisements for online shopping, insurance companies, and cell phone plans (Statista, 2022). Furthermore, a number of mental health advertising campaigns are on the rise. Ma...

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive obsessive thoughts and compulsive behaviors. Multiple studies have shown the association of polymorphisms in the SLC1A1 gene with OCD. The most common of these OCD-associated polymorphisms increases the expression of the encoded protein, excitatory amino acid transporter 3 (EAAT3), a neuronal glutamate transporter. Previous work has shown that increased EAAT3 expression results in OCD-relevant behavioral phenotypes in rodent models. In this study, we created a novel mouse model with targeted, reversible overexpression of Slc1a1 in forebrain neurons. The mice do not have a baseline difference in repetitive behavior but show increased hyperlocomotion following a low dose of amphetamine (3 mg/kg) and increased stereotypy following a high dose of amphetamine (8 mg/kg). We next characterized the effect of amphetamine on striatal cFos response and found that amphetamine increased cFos throughout the striatum in ...

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the moto...

Laboratory outreach programs for K-12 students in the United States from 2020 to 2022 were suspended or delayed due to COVID-19 restrictions. While Southern Nevada also observed similar closures for onsite programs, we and others hypothesized that in-person laboratory activities could be prioritized after increasing vaccine doses were available to the public and masking was encouraged. Here, we describe how the Laboratory of Neurogenetics and Precision Medicine at the University of Nevada Las Vegas (UNLV) collaborated with administrators from a local school district to conduct training activities for high school students during the COVID-19 pandemic. The Science Education for the Youth (SEFTY) program's curriculum was constructed to incorporate experiential learning, fostering collaboration and peer-to-peer knowledge exchange. Leveraging neuroscience tools from our UNLV laboratory, we engaged with 117 high school applicants from 2021 to 2022. Our recruitment efforts yielded a diverse cohort, with >41% Paci...