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Michaelides, M.

Publications and source records attributed to Michaelides, M..

2 recordsLinked to original sources

High-accuracy Decoding of Complex Visual Scenes from Neuronal Calcium Responses

The brain contains billions of neurons defined by diverse cytoarchitectural, anatomical, genetic, and functional properties. Sensory encoding and decoding are popular research areas in the fields of neuroscience, neuroprosthetics and artificial intelligence but the contribution of neuronal diversity to these processes is not well understood. Deciphering this contribution necessitates development of sophisticated neurotechnologies that can monitor brain physiology and behavior via simultaneous assessment of individual genetically-defined neurons during the presentation of discrete sensory cues and behavioral contexts. Neural networks are a powerful technique for formulating hierarchical representations of data using layers of nonlinear transformations. Here we leverage the availability of an unprecedented collection of neuronal activity data, derived from [~]25,000 individual genetically-defined neurons of the parcellated mouse visual cortex during the presentation of 118 unique and complex naturalistic scenes, to demonstrate that neural networks can be used to decode discrete visual scenes from neuronal calcium responses with high ([~]96%) accuracy. Our findings highlight the novel use of neural networks for sensory decoding using neuronal calcium imaging data and reveal a neuroanatomical map of visual decoding strength traversing brain regions, cortical layers, neuron types, and time. Our findings also demonstrate the utility of feature selection in assigning contributions of neuronal diversity to visual decoding accuracy and the low requirement of network architecture complexity for high accuracy decoding in this experimental context.

neuroscience

Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been assigned by linkage to two loci, MCDR1 on chromosome 6q16 and MCDR3 on chromosome 5p15-p13. Recently, noncoding variants upstream of PRDM13 and a large duplication including IRX1 have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine NCMD families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD at the MCDR3 locus and provide insights into the genetic pathways involved in human macular development.\n\nAbbreviations list

genomics