Goal-tracking (GT) rats are sensitive to Pavlovian outcome devaluation while sign-tracking (ST) rats are devaluation insensitive. During outcome devaluation, GT rats flexibly modify responding to cues based on the current value of the associated outcome. However, ST rats rigidly respond to cues regardless of the current outcome value. Prior work demonstrated disconnection of the basolateral amygdala (BLA) and anterior insular cortex (aIC) decreased both GT and ST behaviors. Given the role of these regions in appetitive motivation and behavioral flexibility, we predicted that disrupting BLA to aIC pathway during outcome devaluation would reduce flexibility in GT rats and reduce rigid appetitive motivation in ST rats. We inhibited the BLA to aIC pathway by infusing inhibitory DREADDs (hM4Di-mcherry) or control (mCherry) virus into the BLA and implanted cannulae into the aIC to inhibit BLA terminals using intracranial injections of clozapine N-oxide (CNO). After training, we used a within - subject satiety-in...

Implantation of guide cannulas is a widely used technique to access specific brain areas. Although commercially available, the need to personalize these implants and the high cost prompted us to design open-source customized devices taking advantage of 3D printing technology. Our cannulas consisted in a 3D-printed head mount designed according to the Paxinos coordinates to reach the CA1 area of the hippocampus. To cut guide cannulas to the proper length, we designed and realized an original 3D-printed linear motion apparatus. Polylactic acid thermoplastic polymer was used as printing material. Homemade or commercial cannulas were implanted in 4- to 6-month-old wild-type mice and intrahippocampal injections of amyloid-β peptide at different concentrations were performed. In vivo behavioral studies of novel object recognition indicated that results obtained with homemade versus commercial devices were comparable. Methylene blue injections and Nissl staining confirmed the correct localization of cannulas in t...

The ability to detect faces in the environment is of utmost ecological importance for human social adaptation. While face categorization is efficient, fast and robust to sensory degradation, it is massively impaired when the facial stimulus does not match the natural contrast statistics of this visual category, i.e., the typically experienced ordered alternation of relatively darker and lighter regions of the face. To clarify this phenomenon, we characterized the contribution of natural contrast statistics to face categorization. Specifically, 31 human adults viewed various natural images of nonface categories at a rate of 12 Hz, with highly variable images of faces occurring every eight stimuli (1.5 Hz). As in previous studies, neural responses at 1.5 Hz as measured with high-density electroencephalography (EEG) provided an objective neural index of face categorization. Here, when face images were shown in their naturally experienced contrast statistics, the 1.5-Hz face categorization response emerged ove...

Our brains synthesize vast and varied sensory inputs to represent an event or place that can later be recalled freely. The term “engram” refers to a group of neurons activated in association with a memory or event, suggesting that if one were to activate a subset of cells in the ensemble, one would trigger the recall of a memory. The medial temporal lobes, including the hippocampus, are often studied as the primary region of spatial engram formation (Josselyn and Tonegawa, 2020). However, newly formed spatial memory representations are incredibly transient. Following encoding, consolidation from the hippocampus to related cortical structures is critical for stable memory retention (Wirt and Hyman, 2017). What happens when this process of generating stable long-term memories is disrupted? Neuronal hyperactivity, seen in seizures, potentially corrupts existing engrams and is often associated with retrograde amnesia in humans. Retrograde amnesia, or forgetting recently formed memories, could be because of dis...

It has been suggested that the dorsomedial striatum (DMS) is engaged in the early stages of motor learning for goal-directed actions, whereas at later stages, control is transferred to the dorsolateral striatum (DLS), a process that enables learned motor actions to become a skill or habit. It is not known whether these striatal regions are simultaneously active while the expertise is acquired. To address this question, we developed a mouse “Treadmill Training Task” that tracks changes in mouse locomotor coordination during running practice and simultaneously provides a means to measure local neuronal activity using photometry. To measure change in motor coordination over treadmill practice sessions, we used DeepLabCut (DLC) and custom-built code to analyze body position and paw movements. By evaluating improvements in motor coordination during training with simultaneous neuronal calcium activity in the striatum, we found that DMS direct pathway neurons exhibited decreased activity as the mouse gained profi...

Three-dimensional neuronal culture systems such as spheroids, organoids, and assembloids constitute a branch of neuronal tissue engineering that has improved our ability to model the human brain in the laboratory. However, the more elaborate the brain model, the more difficult it becomes to study functional properties such as electrical activity at the neuronal level, similar to the challenges of studying neurophysiology in vivo . We describe a simple approach to generate self-assembled three-dimensional neuronal spheroid networks with defined human cell composition on microelectrode arrays. Such spheroid networks develop a highly three-dimensional morphology with cell clusters up to 60 μm in thickness and are interconnected by pronounced bundles of neuronal fibers and glial processes. We could reliably record from up to hundreds of neurons simultaneously per culture for ≤90 d. By quantifying the formation of these three-dimensional structures over time, while regularly monitoring electrical activity, we w...

Running wheels for mice residing in the home cage are useful for the continuous measurement of locomotor activity for studies testing exercise interventions or exercise-induced effects on brain and metabolism. Here, we have developed an open source, printable, open-faced running wheel that is automated to collect locomotor information such as distance traveled, wheel direction, and velocity that can be binned into epochs over 24 h or multiple days. This system allows for remote data collection to avoid human interference in mouse behavioral experiments. We tested this system in an activity-based anorexia procedure. Using these wheels, we replicate previous findings that food restriction augments wheel-running activity.

Recently, a new generation of devices have been developed to record neural activity simultaneously from hundreds of electrodes with a very high spatial density, both for in vitro and in vivo applications. While these advances enable to record from many more cells, they also challenge the already complicated process of spike sorting (i.e., extracting isolated single-neuron activity from extracellular signals). In this work, we used synthetic ground-truth recordings with controlled levels of correlations among neurons to quantitatively benchmark the performance of state-of-the-art spike sorters focusing specifically on spike collisions. Our results show that while modern template-matching-based algorithms are more accurate than density-based approaches, all methods, to some extent, failed to detect synchronous spike events of neurons with similar extracellular signals. Interestingly, the performance of the sorters is not largely affected by the spiking activity in the recordings, with respect to average firi...

Almost every industry had a deer-in-the-headlights moment when the COVID-19 pandemic forced the world to a halt. The education field was faced with an unprecedented situation. How do we continue our instruction with this bizarre reality that we must accept as the new normal? Educators from kindergarten to university levels had to urgently adapt their ways to keep the mission of education alive. While some teaching methods remained effective despite remote learning and “Zoom school,” some were simply not possible to implement given social distancing and occupancy restriction guidelines at the time. As an undergraduate neuroscience educator, one daunting dilemma was how to continue laboratory research training of our young neuroscientists. Universities across the country had to send students home and restrict access to campuses. Many of our undergraduate neuroscience students are on premedical tracks, and these restrictions added much more complexity to their goals of meeting medical school requirements of s...

In the article “A Novel Neuron-Specific Regulator of the V-ATPase in Drosophila ,” by Amina Dulac, Abdul-Raouf Issa, Jun Sun, Giorgio Matassi, Célia Jonas, Baya Chérif-Zahar, Daniel Cattaert, and Serge …