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Biology subjects

Cervera, R. L.

Publications and source records attributed to Cervera, R. L..

2 recordsLinked to original sources

Prefrontal control of actions in freely moving macaques

Our natural behavioral repertoires include complex coordinated actions of characteristic types. To better understand the organization of action and its neural underpinnings, we examined behavior and neural activity in rhesus macaques performing a freely moving foraging task in an open environment. We developed a novel analysis pipeline that can identify meaningful units of behavior, corresponding to recognizable actions such as sitting, walking, jumping, and climbing. On the basis of action transition probabilities, we found that behavior was organized in a modular and hierarchical fashion. We found that, after regressing out many potential confounders, actions are associated with specific patterns of firing in each of six prefrontal brain regions and that, overall, representation of actions is progressively stronger in more dorsal and more caudal prefrontal regions. Conversely, we found that switching between actions resulted in changed firing rates, with more rostral and more ventral regions showing stronger effects. Together, these results establish a link between control of action state and neuronal activity in prefrontal regions in the primate brain.

neuroscience↗

A Genetic Model Therapy Proposes a Critical Role for Liver Dysfunction in Mitochondrial Biology and Disease

The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Here we present a new animal model that recapitulates key components of Leigh Syndrome, French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the Leucine Rich Pentatricopeptide repeat-containing motif (LRPPRC) gene. LRPPRC has native functions related to mitochondrial mRNA polyadenylation and translation as well as a role in gluconeogenesis. We used the Gene-Breaking Transposon (GBT) cassette to create a revertible, insertional mutant zebrafish line in the LRPPRC gene. lrpprc zebrafish homozygous mutants displayed impaired muscle development, liver function and lowered levels of mtDNA transcripts and are lethal by 12dpf, all outcomes similar to clinical phenotypes observed in patients. Investigations using an in vivo lipidomics approach demonstrated accumulation of non-polar lipids in these animals. Transcript profiling of the mutants revealed dysregulation of clinically important nuclearly encoded and mitochondrial transcripts. Using engineered liver-specific rescue as a genetic model therapy, we demonstrate survival past the initial larval lethality, as well as restored normal gut development, mitochondrial morphology and triglyceride levels functionally demonstrating a critical role for the liver in the pathophysiology of this model of mitochondrial disease. Understanding the molecular mechanism of the liver-mediated genetic rescue underscores the potential to improve the clinical diagnostic and therapeutic developments for patients suffering from these devastating disorders.

genetics↗