Early and accurate diagnosis of Alzheimer's disease (AD) will be key for effective personalized treatment plans ( [Cummings, 2023][1]). Significant difficulties in auditory processing have been frequently reported in many patients with mild cognitive impairment, the prodromal form of AD ( [Tarawneh et al., 2022][2]), making it an outstanding candidate as AD diagnostic biomarker. However, the efficiency of diagnosis with this parameter has not been explored. Here we show that when male mice with amyloidosis begin to show memory decline, changes in the auditory brainstem response (ABR) to clicks enable the reliable diagnosis of disease using a machine learning algorithm. Interpretation of the machine learning diagnosis revealed that the upper levels of the auditory pathway, including the inferior colliculus, were the probable sources of the defects. Histological analyses show that in these locations, neuroinflammation and plaque deposition temporally correlate with behavioral changes consistent with memory l...

Mouse lines with tetracycline-controlled gene expression in specific neuronal populations provide valuable tools for studying their development, function, connectivity, and pathology in vivo. Our initial goal was to generate a mouse model that could express amyotrophic lateral sclerosis-associated genes specifically in spinal cord motor neurons under the control of the HB9 promoter. However, HB9-tTA mice unexpectedly direct target gene expression in a small subset of dorsal horn neurons. These mice represent a new tool for scientists who are interested in studying these spinal cord neurons.

The importance of animal models to an understanding of the development and plasticity of visual functions was evident from the outset of the long experimental collaboration of David Hubel and Torsten Wiesel in the early 1960s. Their initial work on kittens had massive impact in part because of the recognition that kittens share with primates substantial similarities of visual system organization and plasticity (e.g., eye-specific lamination of the thalamus and columnar organization of the visual cortex), as well as comparable visual abilities (including stereoscopic vision). In addition the plasticity demonstrated in response to early periods of selected visual exposure provided a glimpse into the origins of amblyopia. Five decades ago my laboratory developed a method for the fast measurement of visual thresholds in kittens in order to capture the consequences for spatial vision of the rapid physiological changes that occurred in the visual cortex during both typical development and those that follow vario...

The scientific landscape in the United States is experiencing a significant shift. Recent developments have created new challenges for US researchers, US institutions, and scientific societies worldwide that warrant our collective attention and thoughtful response. These changes present an opportunity to reaffirm the fundamental importance of scientific exchange. Recent policy changes have significantly altered funding for biomedical research in the United States. The National Institutes of Health (NIH) has announced substantial reductions in funding and has canceled study sections. Although the story is still unravelling, the decision to limit the overheads to 15% may threaten the very existence of some laboratories with obvious disastrous human consequences. This also includes the closure of NIH-core funded facilities and the firing of scientific personnel. The current climate has changed the way international researchers consider future travel to the United …

In the article “Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation,” by Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, and Ana João Rodrigues, …

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms. Its pathological hallmarks include the accumulation of misfolded alpha-synuclein (α-Syn) in Lewy bodies and Lewy neurites. Phosphorylation of α-Syn is a prominent feature of these inclusions, but its role in disease pathogenesis remains unclear. To identify the role of α-Syn phosphorylation in synucleinopathy, we generated two Snca knock-in (KI) mouse models carrying phosphomimetic mutations at SncaY39 or SncaS129 ( SncaY39E or SncaS129D ) which manipulated epitopes phosphorylated in the PD brain. Both SncaY39E and SncaS129D KI mice displayed increased α-Syn phosphorylation, enhanced oligomer formation, and a shift of α-Syn localization from membrane-bound to cytoplasm. However, neurodegeneration in the substantia nigra was not observed up to 24 months of age. These findings demonstrate that mimicking the phosphorylation of Y39 or S129 can induce endogenous α-Syn phosphorylation. Still, a sing...

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Its pathological hallmarks include the accumulation of misfolded alpha-Synuclein (α-Syn) in Lewy bodies (LBs) and Lewy neurites. Phosphorylation of α-Syn is a prominent feature of these inclusions, but its role in disease pathogenesis remains unclear. To identify the role of α-Syn phosphorylation in Synucleinopathy, we generated two Snca knock-in (KI) mouse models carrying phosphomimetic mutations at SncaY39 or SncaS129 ( SncaY39E or SncaS129D ) which manipulated epitopes phosphorylated in PD brain. Both SncaY39E and SncaS129D KI mice displayed increased α-Syn phosphorylation, enhanced oligomer formation, and a shift of α-Syn localization from membrane-bound to cytoplasm. However, neurodegeneration in substantia nigra was not observed up to 24 months of age. These findings demonstrate that mimicking the phosphorylation of Y39 or S129 can induce endogenous α-Syn phosphorylation. Still, a singl...

The SfN annual meeting has excellent opportunities to make meaningful connections and seek real-time information. Here are a few ways you can personalize your experience.

Organized by the FENS-Kavli Network of Excellence (FKNE) under the umbrella of the FENS Committee of Higher Education and Training (CHET), this session focuses on topics relevant for senior postdocs and newly appointed PIs who want to start their own lab, including: - How to get your first PI position. - Selection of team members. - Application and management of funds. - Early career mobility. - Balancing family with career.

The crisis of reproducibility in biology, from which neuroscience is not immune, has many causes. This workshop covers the wide-ranging issues that contribute to irreproducibility. It focuses on the bias in dissemination of experimental data from the point of view of journals, funding agencies, and the general media.