Mitochondrial Ca²⁺ Uniporter haploinsufficiency enhances long-term potentiation at hippocampal mossy fibre synapses

Long-term changes in synaptic strength form the basis of learning and memory. These changes rely upon energy demanding mechanisms which are regulated by local Ca2+ signaling. Mitochondria are optimised for providing energy and buffering Ca2+. However, our understanding of the role of mitochondria in regulating synaptic plasticity is incomplete. Here we have used optical and electrophysiological techniques in cultured hippocampal neurons and ex vivo hippocampal slices from mice with haploinsufficiency of the mitochondrial Ca2+ uniporter (MCU+/-) to address whether reducing mitochondrial Ca2+ uptake alters synaptic transmission and plasticity. We found that cultured MCU+/- hippocampal neurons have impaired Ca2+ clearance, and consequently enhanced synaptic vesicle fusion at presynapses occupied by mitochondria. Furthermore, long-term potentiation (LTP) at mossy fibre (MF) synapses, a process which is dependent on presynaptic Ca2+ accumulation, is enhanced in MCU+/- slices. Our results reveal a previously unrecognized role for mitochondria in regulating presynaptic plasticity of a major excitatory pathway involved in learning and memory

Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition.

Altered excitatory/inhibitory (E/I) balance is implicated in neuropsychiatric and neurodevelopmental disorders, but the underlying genetic etiology remains poorly understood. Copy number variations in CYFIP1 are associated with autism, schizophrenia, and intellectual disability, but its role in regulating synaptic inhibition or E/I balance remains unclear. We show that CYFIP1, and the paralog CYFIP2, are enriched at inhibitory postsynaptic sites. While CYFIP1 or CYFIP2 upregulation increases excitatory synapse number and the frequency of miniature excitatory postsynaptic currents (mEPSCs), it has the opposite effect at inhibitory synapses, decreasing their size and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Contrary to CYFIP1 upregulation, its loss in vivo, upon conditional knockout in neocortical principal cells, increases expression of postsynaptic GABAA receptor β2/3-subunits and neuroligin 3, enhancing synaptic inhibition. Thus, CYFIP1 dosage can bi-directionally impact inhibitory synaptic structure and function, potentially leading to altered E/I balance and circuit dysfunction in CYFIP1-associated neurological disorders

Three-Dimensional Printing of a Scalable Molecular Model and Orbital Kit for Organic Chemistry Teaching and Learning

Three-dimensional (3D) chemical models are a well-established learning tool used to enhance the understanding of chemical structures by converting two-dimensional paper or screen outputs into realistic three-dimensional objects. While commercial atom model kits are readily available, there is a surprising lack of large molecular and orbital models that could be used in large spaces. As part of a program investigating the utility of 3D printing in teaching, a modular size-adjustable molecular model and orbital kit was developed and produced using 3D printing and was used to enhance the teaching of stereochemistry, isomerism, hybridization, and orbitals

Breaking the Access to Education Barrier: Enhancing HPLC Learning with Virtual Reality Digital Twins

This research focuses on an innovative approach to High Performance Liquid Chromatography (HPLC) practical teaching, specifically exploring the application of Virtual Reality (VR) digital twin models to revolutionize undergraduate education. Traditionally, the exposure to HPLC instrumentation for undergraduates has been severely limited due to the substantial student population and the prohibitively high costs of these systems. To surmount these constraints, we designed and developed custom in-house multi-user VR software and created a VR digital twin model of the HPLC instrument in a training environment containing multiple HPLCs, aiming to simulate a realistic, interactive, and immersive learning environment. The investigation included a group of undergraduates with no previous HPLC experience, assessing the effectiveness of the VR digital twin model juxtaposed with conventional teaching methods. Results exhibited a marked improvement in student comprehension of HPLC and their engagement levels, with the VR digital twin model serving as a significant enhancer. Notably, students reported a heightened confidence in their operational understanding of the instrument and exhibited a more profound grasp of the underlying theoretical concepts. In light of these findings, we propose that VR digital twin models can revolutionize practical teaching, particularly in areas constrained by equipment accessibility. This paper, therefore, offers compelling insights into the transformative potential of VR digital twin models in reshaping HPLC practical teaching in undergraduate education

Breaking the Access to Education Barrier: Enhancing HPLC Learning with Virtual Reality

This research focuses on an innovative approach to the practical teaching of High Performance Liquid Chromatography (HPLC), specifically exploring the application of Virtual Reality (VR) in undergraduate education. Traditionally, the exposure to HPLC instrumentation for undergraduates has been limited due to a substantial student population and the prohibitively high costs of these systems. To overcome these challenges, we developed our own in-house multi-user VR software, as well as a VR digital twin model of HPLC instruments in our laboratory and placed multiple copies of these in a training environment, aiming to simulate a realistic, interactive, and immersive learning HPLC environment. The investigation of its effectiveness included a group of first year undergraduate students with no previous HPLC experience, aiming to assess the reception of the VR learning environment among a student cohort. The use of the VR software positively influenced student engagement with HPLC training. Survey results indicate that the majority of students greatly enjoyed the VR sessions, with many students reporting a heightened interest in practicals and self-reporting that they learned better than they would have using text or PowerPoints, though formal assessment is needed to quantify its impact on learning outcomes. Notably, students reported a heightened confidence in their operational understanding of the instrument and exhibited a more profound grasp of the underlying theoretical concepts. In light of these findings, we propose that VR learning environments equipped with digital twins of laboratory equipment can greatly enhance practical teaching, particularly in areas constrained by equipment accessibility. This work, therefore, offers compelling insights into the potential of VR learning environments in reshaping HPLC practical teaching in undergraduate education