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...

Fredrick John Seil, MD was born on November 9, 1933 of German parentage in the town of Neu schowe (Nove Sove) in the former Yugoslavia (now Ravno Selo, Serbia). He emigrated with his family to the United States in March of 1938.

Investigation of neural processes underlying motor control requires behavioral readouts that capture the richness of actions, including both categorical (choice-based) information and motor execution (kinematics). We present an open-source platform for behavioral training of head-fixed mice that combines a stationary or retractable forelimb-based joystick, sound-presentation system, capacitive lick sensor, and water reward dispenser. The setup allows for the creation of multiple behavioral paradigms, two of which are highlighted here: a two-alternative forced-choice auditory-motor discrimination paradigm and a two-armed bandit value-based decision-making task. In the auditory-motor paradigm, mice learn to report high- or low-frequency tones by pushing or pulling the joystick. In the value-based paradigm, mice learn to push or pull the joystick based on the history of rewarded trials. In addition to reporting categorical choices, this setup provides a rich dataset of motor parameters that reflect components...

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by specific morphological and electrophysiological properties. First, in ∼90% of the cases, their axon arises from an axon-bearing dendrite (ABD) at highly variable distances from the soma. Second, they display a highly regular pattern of spontaneous activity (aka pacemaking) and a broad action potential (AP) that faithfully back-propagate through the entire dendritic arbor. In previous studies (Moubarak et al., 2019; Moubarak et al., 2022), we demonstrated that the presence of a high density of sodium current in the ABD and the complexity of this dendrite played a critical role in the robustness of pacemaking and setting the half-width of the AP. In the current study, we investigated the postnatal development of both morphology and AP shape in SNc DA neurons in order to determine when and how the mature electrophysiological phenotype of these neurons was achieved. To do so, we performed electrophysiological recordings of SNc ...

Operant conditioning (OC) is a classical paradigm and a standard technique used in experimental psychology in which animals learn to perform an action to achieve a reward. By using this paradigm, it is possible to extract learning curves and measure accurately reaction times (RTs). Both these measurements are proxy of cognitive capabilities and can be used to evaluate the effectiveness of therapeutic interventions in mouse models of disease. Here, we describe a fully 3D printable device that is able to perform OC on freely moving mice, while performing real-time tracking of the animal position. We successfully trained six mice, showing stereotyped learning curves that are highly reproducible across mice and reaching >70% of accuracy after 2 d of conditioning. Different products for OC are commercially available, though most of them do not provide customizable features and are relatively expensive. This data demonstrate that this system is a valuable alternative to available state-of-the-art commercial devi...

To successfully navigate our daily environment, humans (as well as non-human organisms) rely on the crucial skill of selecting perceptual information into relevant categories (e.g. ‘things that are edible’, ‘things that are dangerous’ etc.). This catego...

Approximately 30% of all women will experience physical intimate partner violence (IPV) in their lifetime. IPV commonly results in physical injury to the head, which could cause significant impairment in psychological processes if a lesion (i.e. injury ...

A decline in cognitive abilities is associated with the aging process, affecting nearly 33% of US adults over the age of 70, and is a risk factor for the development of dementia and Alzheimer's disease. Several studies have reported age-related alterations in the transcriptome in the hippocampus, a major site of memory storage that is among the first regions impacted with age, dementia, and Alzheimer's disease. However, much remains unknown about why these transcriptional changes exist in the aged hippocampus and how this impacts memory late in life. Here, we show that monoubiquitination of histone H2B (H2Bubi), an epigenetic mechanism recently reported to be major regulator of the epigenome and transcriptome during memory formation in the young adult brain, decreases with age in the hippocampus of male rats. In vivo CRISPR-dCas9–mediated upregulation of Rnf20 , the only ubiquitin E3 ligase for H2B, in the hippocampus significantly improved memory retention in aged rats. Remarkably, RNA-seq analysis reveal...

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...

Amyloidogenic processing of beta-amyloid precursor protein (APP) by beta-secretase and Presenilin (PS) /gamma-secretase releases the beta-amyloid (Abeta) and the intracellular domain of APP (AICD). Abeta is the prime culprit for the pathogenesis of Alzh...