Forming long-term memories is crucial for adaptive behavior and survival in changing environments. The molecular consolidation processes which underlie the formation of these long-term memories are dependent on protein synthesis in excitatory and SST-expressing neurons. A centrally important, parallel process to this involves the removal of the memory constraint quinone reductase 2 (QR2), which has been recently shown to enhance memory consolidation for novel experiences in the cortex and hippocampus, via redox modulation. However, it is unknown within which cell type in the cortex removal of QR2 occurs, nor how this affects neuronal function. Here, we use novel taste learning in the mouse anterior insular cortex (aIC) to show that similarly to mRNA translation, QR2 removal occurs in excitatory and SST-expressing neurons. Interestingly, both novel taste and QR2 inhibition reduce excitability specifically within SST, but not excitatory neurons. Furthermore, reducing QR2 expression in SST, but not in PV or e...

Relapse is a major challenge to the treatment of substance use disorders. A progressive increase in cue-induced drug craving, termed incubation of craving, is observed after withdrawal from multiple drugs of abuse in humans and rodents. Incubation of cocaine craving involves the strengthening of excitatory synapses onto nucleus accumbens (NAc) medium spiny neurons via postsynaptic accumulation of high-conductance Ca2+-permeable AMPA receptors. This enhances reactivity to drug-associated cues and is required for the expression of incubation. Additionally, incubation of cocaine craving is associated with loss of the synaptic depression normally triggered by stimulation of metabotropic glutamate receptor 5 (mGlu5), leading to endocannabinoid production, and expressed presynaptically via cannabinoid receptor 1 activation. Previous studies have found alterations in mGlu5 and Homer proteins associated with the loss of this synaptic depression. Here we conducted coimmunoprecipitation studies to investigate associ...

Epilepsy affects 3.4 million people in the United States, and, despite the availability of numerous antiepileptic drugs, 36% of patients have uncontrollable seizures, which severely impact quality of life. High-frequency oscillations (HFOs) are a potential biomarker of epileptogenic tissue that could be useful in surgical planning. As a result, research into the efficacy of HFOs as a clinical tool has increased over the last 2 decades. However, detection and identification of these transient rhythms in intracranial electroencephalographic recordings remain time-consuming and challenging. Although automated detection algorithms have been developed, their results are widely inconsistent, reducing reliability. Thus, manual marking of HFOs remains the gold standard, and manual review of automated results is required. However, manual marking and review are time consuming and can still produce variable results because of their subjective nature and the limitations in functionality of existing open-source softwar...

Gustometers have made it possible to deliver liquids in functional magnetic resonance imaging (fMRI) settings for decades, and mouthpieces are a critical part of these taste delivery systems. Here, we propose an innovative 3D-printed fMRI mouthpiece inspired by children’s pacifiers, allowing human participants to swallow while lying down in an MRI scanner. We used a large sample to validate the effectiveness of our method. The results suggest that the mouthpiece can be used to deliver taste stimuli by showing significant clusters of activation in the insular and piriform cortex, which are regions that have been consistently identified in taste processing. This mouthpiece fulfills several criteria guaranteeing a gustatory stimulus of quality, making the delivery precise and reliable. Moreover, this new pacifier-shaped design is simple and cheap to manufacture, hygienic, comfortable to keep in the mouth, and flexible to use in diverse cases. We hope that this new method will promote and facilitate the study ...

Although we use our visual and tactile sensory systems interchangeably for object recognition on a daily basis, little is known about the mechanism underlying this ability. This study examined how 3D shape features of objects form two congruent and interchangeable visual and tactile perceptual spaces in healthy male and female participants. Since active exploration plays an important role in shape processing, a virtual reality environment was used to visually explore 3D objects called digital embryos without using the tactile sense. In addition, during the tactile procedure, blindfolded participants actively palpated a 3D-printed version of the same objects with both hands. We first demonstrated that the visual and tactile perceptual spaces were highly similar. We then extracted a series of 3D shape features to investigate how visual and tactile exploration can lead to the correct identification of the relationships between objects. The results indicate that both modalities share the same shape features to...

Spontaneous recognition memory tasks are widely used to assess cognitive function in rodents and have become commonplace in the characterization of rodent models of neurodegenerative, neuropsychiatric and neurodevelopmental disorders. Leveraging an animal’s innate preference for novelty, these tasks use object exploration to capture the what, where and when components of recognition memory. Choosing and optimizing objects is a key feature when designing recognition memory tasks. Although the range of objects used in these tasks varies extensively across studies, object features can bias exploration, influence task difficulty and alter brain circuit recruitment. Here, we discuss the advantages of using 3D-printed objects in rodent spontaneous recognition memory tasks. We provide strategies for optimizing their design and usage, and offer a repository of tested, open-source designs for use with commonly used rodent species. The easy accessibility, low-cost, renewability and flexibility of 3D-printed open-sou...

The transcription factor cAMP response element-binding protein (CREB) is involved in a myriad of cellular functions in the central nervous system. For instance, the role of CREB via phosphorylation at the amino-acid residue Serine (Ser)133 in expressing plasticity-related genes and activity-dependent neuronal plasticity processes has been extensively demonstrated. However, much less is known about the role of CREB phosphorylation at Ser142 and Ser143. Here, we employed a viral vector containing a dominant negative form of CREB, with serine-to-alanine mutations at residue 142 and 143 to specifically block phosphorylation at both sites. We then transfected this vector into primary neurons in vitro or intracortically injected it into mice in vivo , to test whether these phosphorylation events were important for activity-dependent plasticity. We demonstrated by immunohistochemistry of cortical neuronal cultures that the expression of Arc, a known plasticity-related gene, requires triple phosphorylation of CREB...

Normal aging is associated with a decline in memory and motor learning ability. However, the exact form of these impairments (e.g., the short-term temporal stability and affected learning mechanisms) is largely unknown. Here, we used a sensorimotor adaptation task to examine changes in the temporal stability of two forms of learning (explicit and implicit) because of normal aging. Healthy young subjects (age range, 19–28 years; 20 individuals) and older human subjects (age range, 63–85 years; 19 individuals) made reaching movements in response to altered visual feedback. On each trial, subjects turned a rotation dial to select an explicit aiming direction. Once selected, the display was removed and subjects moved the cursor from the start position to the target. After initial training with the rotational feedback perturbation, subjects completed a series of probe trials at different delay periods to systematically assess the short-term retention of learning. For both groups, the explicit aiming showed no s...

Dopaminergic modulation is essential for the control of voluntary movement; however, the role of dopamine in regulating the neural excitability of the primary motor cortex (M1) is not well understood. Here, we investigated two modes by which dopamine influences the input/output function of M1 neurons. To test the direct regulation of M1 neurons by dopamine, we performed whole-cell recordings of excitatory neurons and measured excitability before and after local, acute dopamine receptor blockade. We then determined whether chronic depletion of dopaminergic input to the entire motor circuit, via a mouse model of Parkinson’s disease, was sufficient to shift M1 neuron excitability. We show that D1 receptor (D1R) and D2R antagonism altered subthreshold and suprathreshold properties of M1 pyramidal neurons in a layer-specific fashion. The effects of D1R antagonism were primarily driven by changes to intrinsic properties, while the excitability shifts following D2R antagonism relied on synaptic transmission. In c...

The V-ATPase is a highly conserved enzymatic complex that ensures appropriate levels of organelle acidification in virtually all eukaryotic cells. While the general mechanisms of this proton pump have been well studied, little is known about the specific regulations of neuronal V-ATPase. Here, we studied CG31030, a previously uncharacterized Drosophila protein predicted from its sequence homology to be part of the V-ATPase family. In contrast to its ortholog ATP6AP1/VhaAC45 which is ubiquitous, we observed that CG31030 expression is apparently restricted to all neurons, and using CRISPR/Cas9-mediated gene tagging, that it is mainly addressed to synaptic terminals. In addition, we observed that CG31030 is essential for fly survival and that this protein co-immunoprecipitates with identified V-ATPase subunits, and in particular ATP6AP2. Using a genetically-encoded pH probe (VMAT-pHluorin) and electrophysiological recordings at the larval neuromuscular junction, we show that CG31030 knock-down induces a major...