A Model of Visually Guided Plasticity of the Auditory Spatial Map in the Barn Owl

In the barn owl, the self-organization of the auditory map of space in the external nucleus of the inferior colliculus (ICx) is strongly influenced by vision, but the nature of this interaction is unknown. In this paper a biologically plausible and minimalistic model of ICx self-organization is proposed where the ICx receives a learn signal based on the owl’s visual attention. When the visual attention is focused in the same spatial location as the auditory input, the learn signal is turned on, and the map is allowed to adapt. A two-dimensional Kohonen map is used to model the ICx, and simulations were performed to evaluate how the learn signal would affect the auditory map. When primary area of visual attention was shifted at different spatial locations, the auditory map shifted to the corresponding location. The shift was complete when done early in the development and partial when done later. Similar results have been observedin the barn owl with its visual field modified with prisms. Therefore, the simulations suggest that a learn signal, based on visual attention, is a possible explanation for the auditory plasticity

Investigation of firing properties in CA1 hippocampal pyramidal neurons in a mouse model of Fragile X syndrome

textFragile X Syndrome is the most common form of heritable cognitive disability. It is caused by a genetic mutation that leads to a lack of protein from the FMR1 gene. This protein (FMRP) is used to regulate the translation of many other proteins, thereby leading to a wide range of effects. Because the origin of this disease is based on the lack of a single protein, an animal model with construct validity can be used to investigate the potential effects leading to the symptoms of the disease. Many studies have investigated the synaptic plasticity differences of CA1 pyramidal neurons between a mouse model of fragile X syndrome (KO) and a wild type mouse (WT). This study investigates the differences in firing properties of a CA1 pyramidal neuron between the KO and WT. Specifically, contributions of two ion channels are investigated: the Ca2+ and voltage activated potassium channel (BK) and the potassium channel (M) inhibited by the muscarinic acetylcholine receptor. This study finds some differences that warrant further investigation, including differences in spike timing, spike width and the initial rate of rise of an action potential. However, several areas of investigation yield subtle or confounding results, which may indicate that the CA1 pyramidal neurons affected by the lack of FMRP may make up more than one population.Neuroscienc

Mitochondrial DNA variation across 56,434 individuals in gnomAD

Genomic databases of allele frequency are extremely helpful for evaluating clinical variants of unknown significance; however, until now, databases such as the Genome Aggregation Database (gnomAD) have focused on nuclear DNA and have ignored the mitochondrial genome (mtDNA). Here, we present a pipeline to call mtDNA variants that addresses three technical challenges: (1) detecting homoplasmic and heteroplasmic variants, present, respectively, in all or a fraction of mtDNA molecules; (2) circular mtDNA genome; and (3) misalignment of nuclear sequences of mitochondrial origin (NUMTs). We observed that mtDNA copy number per cell varied across gnomAD cohorts and influenced the fraction of NUMT-derived false-positive variant calls, which can account for the majority of putative heteroplasmies. To avoid false positives, we excluded contaminated samples, cell lines, and samples prone to NUMT misalignment due to few mtDNA copies. Furthermore, we report variants with heteroplasmy ≥10%. We applied this pipeline to 56,434 whole-genome sequences in the gnomAD v3.1 database that includes individuals of European (58%), African (25%), Latino (10%), and Asian (5%) ancestry. Our gnomAD v3.1 release contains population frequencies for 10,850 unique mtDNA variants at more than half of all mtDNA bases. Importantly, we report frequencies within each nuclear ancestral population and mitochondrial haplogroup. Homoplasmic variants account for most variant calls (98%) and unique variants (85%). We observed that 1/250 individuals carry a pathogenic mtDNA variant with heteroplasmy above 10%. These mtDNA population allele frequencies are freely accessible and will aid in diagnostic interpretation and research studies