Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice.

Background: The cannabinoid receptor 2 (CB2R), a cannabinoid receptor primarily expressed in immune cells, has been found in the brain, particularly in the hippocampus, where it plays crucial roles in modulating various neural functions, including synaptic plasticity, neuroprotection, neurogenesis, anxiety and stress responses, and neuroinflammation. Despite this growing understanding, the intricate electrophysiological characteristics of hippocampal neurons in CB2R knockout (CB2R KO) mice remain elusive. Aim and Methods: This study aimed to comprehensively assess the electrophysiological traits of hippocampal synaptic and network functions in CB2R KO mice. The focus was on aspects such as synaptic transmission, short- and long-term synaptic plasticity, and neural network synchrony (theta oscillations). Results: Our findings unveiled multiple functional traits in these CB2R KO mice, notably elevated synaptic transmission in hippocampal CA1 neurons, decreased both synaptic short-term plasticity (paired-pulse facilitation) and long-term potentiation (LTP), and impaired neural network synchronization. Conclusion: In essence, this study yields insightful revelations about the influence of CB2Rs on hippocampal neural functions. By illuminating the electrophysiological modifications in CB2R KO mice, our research enriches the comprehension of CB2R involvement in hippocampal function. Such insights could hold implications for advancing our understanding of the neural mechanisms under the influence of CB2Rs within the brain.

Effects of valproate on seizure-like activity in Drosophila melanogaster with a knockdown of Ube3a in different neuronal populations as a model of Angelman Syndrome.

Angelman Syndrome is a rare, genetically induced neurodevelopmental disorder. This disorder stems from a mutation or deletion of the maternal UBE3A gene. Characteristics of this disease include developmental delay, recurring seizures, and severe intellectual disabilities. We studied seizure activity in male Drosophila melanogaster with a knockdown of Ube3a in different neuronal populations (GABAergic, glutamatergic, mushroom body, and all neurons) and investigated the effects of the antiseizure medication (ASM) on seizure-like activity. Epileptiform activity was monitored in individual fruit flies using imaging chambers and mechanically induced seizures using a vortex assay. A positive control was also used: eas (easily shocked seizure phenotype). Seizure activity was analyzed for sums of seizure durations, number of seizures, and total time to return to normal activity. Ube3a knockdowns in GABAergic neurons elicited more seizure-like episodes than knockdowns in glutamatergic neurons and were on par with the positive control group and those with knockdowns in the mushroom bodies. We have established a method whereby valproate could be administered through food rather than through injections to effectively treat epileptiform activity. We demonstrated that if Ube3a is not knocked down pan-neuronally, Angelman Syndrome seizure-like activity can be studied using Drosophila melanogaster and therefore allows for high-throughput drug discovery.

Cell Fate Decision Making through Oriented Cell Division.

The ability to dictate cell fate decisions is critical during animal development. Moreover, faithful execution of this process ensures proper tissue homeostasis throughout adulthood, whereas defects in the molecular machinery involved may contribute to disease. Evolutionarily conserved protein complexes control cell fate decisions across diverse tissues. Maintaining proper daughter cell inheritance patterns of these determinants during mitosis is therefore a fundamental step of the cell fate decision-making process. In this review, we will discuss two key aspects of this fate determinant segregation activity, cortical cell polarity and mitotic spindle orientation, and how they operate together to produce oriented cell divisions that ultimately influence daughter cell fate. Our focus will be directed at the principal underlying molecular mechanisms and the specific cell fate decisions they have been shown to control.