Each stage of a scientist's career is filled with unique challenges that seem like roadblocks to becoming an advocate. Graduate school is no exception, but early career scientists should be advocating for science, as what this year’s budget provides can alter our career trajectories. As a graduate student, I first thought there wasn’t much I could do, and that advocacy could only be effective if it was intense and all consuming. Even if I figured out what to do, it seemed like it would be too much. I soon found this assumption to be false.

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...

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.

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...

One pending question in social neuroscience is whether interpersonal interactions are processed differently by the brain depending on the bodily characteristics of the interactor, i.e., their physical appearance. To address this issue, we engaged participants in a minimally interactive task with an avatar either showing bodily features or not while recording their brain activity using electroencephalography (EEG) in order to investigate indices of action observation and action monitoring processing. Multivariate results showed that bodily compared with nonbodily appearance modulated parieto-occipital neural patterns throughout the entire duration of the observed movement and that, importantly, such patterns differ from the ones related to initial shape processing. Furthermore, among the electrocortical indices of action monitoring, only the early observational positivity (oPe) was responsive to the bodily appearance of the observed agent under the specific task requirement to predict the partner movement. ...

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+...

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...

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 primary motor cortex (M1) is strongly engaged by movement planning and execution. However, the role of M1 activity in voluntary grasping is still not completely understood. Here we analyze recordings of M1 neurons during the execution of a delayed reach-to-grasp task, where monkeys had to actively grasp an object with either a side or a precision grip, and then pull it with a low or high amount of force. Single cell and neural populations analyses showed that grip type was robustly and specifically encoded by a large population of neurons, while force level was weakly and transiently encoded within mixed-selective neurons that also encoded grip type. Notably, the grip type was stably decoded from motor cortical populations during the preparation and execution epochs of the task. Our results are consistent with the idea that planning and performing specific grasping movements are high-level skills that strongly engage M1 neurons, while the execution of pulling force might be prominently encoded at lower...