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...

Individuals with normal hearing exhibit considerable variability in their capacity to understand speech in noisy environments. Previous research suggests the cause of this variance may be due to individual differences in cognition and auditory perception. To investigate the impact of cognitive and perceptual differences on speech comprehension, 25 adult human participants with normal hearing completed numerous cognitive and psychoacoustic tasks including the Flanker, Stroop, Trail Making, reading span, and temporal fine structure tests. They also completed a continuous multitalker spatial attention task while neural activity was recorded using electroencephalography. The auditory cortical N1 response was extracted as a measure of neural speech encoding during continuous speech listening using an engineered “chirped-speech” (Cheech) stimulus. We compared N1 component morphologies of target and masker speech stimuli to assess neural correlates of attentional gains while listening to concurrently played short...

Chronic pain affects millions globally, yet no universally effective treatment exists. The primary motor cortex (M1) has been a key target for chronic pain therapies, with electrical stimulation of the M1 (eMCS) showing promise. However, the mechanisms underlying M1-mediated analgesic effects are not fully understood. We investigated the role of the primary somatosensory cortex (S1) in M1-mediated analgesia using a neuropathic pain mouse model. In this model, neuropathic pain is associated with increased spontaneous activity of layer V pyramidal neurons (LV-PNs) in the S1, partly attributed to the reduced activity of somatostatin-expressing inhibitory neurons (SST+ INs), which normally suppress LV-PNs. While manipulation of either LV-PNs or SST+ INs has been shown to alleviate pain, the role of S1 in M1-mediated analgesia has not been identified. Using multichannel silicon probes, we applied eMCS to neuropathic mice and observed significant analgesia. Histological analyses revealed that eMCS activated SST+...

What the basal ganglia do is an oft-asked question; answers range from the selection of actions to the specification of movement to the estimation of time. Here, I argue that how the basal ganglia do what they do is a less-asked but equally important question. I show that the output regions of the basal ganglia create a stringent computational bottleneck, both structurally, because they have far fewer neurons than do their target regions, and dynamically, because of their tonic, inhibitory output. My proposed solution to this bottleneck is that the activity of an output neuron is setting the weight of a basis function, a function defined by that neuron’s synaptic contacts. I illustrate how this may work in practice, allowing basal ganglia output to shift cortical dynamics and control eye movements via the superior colliculus. This solution can account for troubling issues in our understanding of the basal ganglia: why we see output neurons increasing their activity during behavior, rather than only decreas...

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 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.