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Gidon, A.

Publications and source records attributed to Gidon, A..

2 recordsLinked to original sources

Burst coding despite unimodal interval distributions

The burst coding hypothesis posits that the occurrence of sudden high-frequency patterns of action potentials constitutes a salient syllable of the neural code. Many neurons, however, do not produce clearly demarcated bursts, an observation invoked to rule out the pervasiveness of this coding scheme across brain areas and cell types. Here we ask how identifiable spike-timing patterns have to be to preserve potent transmission of information. Should we expect that neurons avoid ambiguous patterns that are neither clearly bursts nor isolated spikes? We addressed these questions using information theory and computational simulations. By quantifying how information transmission depends on firing statistics, we found that the information transmitted is not strongly influenced by the presence of clearly demarcated modes in the interspike interval distribution, a feature often used to identify the presence of burst coding. Instead, we found that neurons having unimodal interval distributions were still able to ascribe different meanings to bursts and isolated spikes. In this regime, information transmission depends on properties of the synapses as well as the length and relative frequency of bursts. Furthermore, we found that common metrics used to quantify burstiness were also unable to predict the degree with which bursts could be used to carry information. Our results provide guiding principles for the implementation of coding strategies based on spike-timing patterns, and show that even unimodal firing statistics can be consistent with a bivariate neural code.

neuroscience

Mitochondrial dysfunction in skeletal muscle of fukutin deficient mice is resistant to exercise- and AICAR-induced rescue

Disruptions in the dystrophin-glycoprotein complex (DGC) are clearly the primary basis underlying various forms of muscular dystrophies and dystroglycanopathies, but the cellular consequences of DGC disruption are still being investigated. Mitochondrial abnormalities are becoming an apparent consequence and contributor to dystrophy disease pathology. Herein, we demonstrate that muscle-specific deletion of the fukutin gene [Myf5/fktn-KO mice (KO)], a model of secondary dystroglycanopathy, results in ~30% lower muscle strength (P<0.001) and 16% lower mitochondrial function (P=0.002) compared to healthy littermate controls (LM). We also observed ~80% lower PGC-1 signaling (P=0.004), a primary transcription factor for mitochondrial biogenesis, in KO mice that likely contributes to the mitochondrial defects. PGC-1 is post-translationally regulated via phosphorylation by AMPK. Treatment with the AMPK agonist AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) failed to rescue mitochondrial deficits in KO mice (P=0.458) but did have beneficial (~30% greater) effects on recovery of muscle contractility following injury in both LM and KO mice compared to saline treatment (P=0.006). The beneficial effects of AMPK stimulation via AICAR on muscle function may be partially explained by AMPKs other role of regulating skeletal muscle autophagy, a cellular process critical for clearance of damaged and/or dysfunctional organelles. Two primary conclusions can be drawn from this data, 1) fukutin deletion produces intrinsic muscular metabolic defects that likely contribute to dystroglycanopathy disease pathology, and 2) AICAR treatment accelerates recovery of muscle function following injury suggesting AMPK signaling as a possible target for therapeutic strategies.

physiology