Biology subjects

Ceballo, S.

Publications and source records attributed to Ceballo, S..

3 recordsLinked to original sources

bioRxiv2022

Emergence of a time-independent population code in auditory cortex enables sound categorization and discrimination learning

The temporal structure of sensory inputs contains essential information for their interpretation by the brain1-9. Sensory systems represent these temporal cues through two codes: the temporal sequences of neuronal activity and the spatial patterns of neuronal firing rate3,7,10-20. However, it is still unknown which of these two coexisting codes causally drives sensory decisions3,10,20,21. To separate their contributions, we designed an optogenetic stimulation paradigm in the mouse auditory cortex to generate neuronal activity patterns differing exclusively along their temporal or spatial dimensions. Training mice to discriminate these patterns shows that they efficiently learn to discriminate spatial but not temporal patterns, indicating that spatial representations are necessary for sensory learning. In line with this result, we observed, based on large-scale neuronal recordings of the auditory system, that the auditory cortex is the first region in which spatial patterns efficiently represent temporal auditory cues varying over several hundred milliseconds. This feature is shared by the deep layers of neural networks trained to categorise time-varying sounds. Therefore, the emergence of a spatial code for temporal sensory cues is a necessary condition to associate temporally structured stimuli to decisions. We expect this constraint to be crucial for re-engineering perception by cortical stimulation.

neuroscience↗

bioRxiv2019

MitoToxy Assay: a novel cell-based method for the assessment of metabolic toxicity in a multiwell plate format using a lactate FRET nanosensor, Laconic

Mitochondrial toxicity is a primary source of pre-clinical drug attrition. Methods that detect mitochondrial toxicity as early as possible during the drug development process are required. Here we introduce a new method for detecting mitochondrial toxicity based on MDA-MB-231 cells stably expressing the genetically-encoded FRET lactate indicator, Laconic. The method takes advantage of the high cytosolic lactate accumulation observed during mitochondrial stress, regardless of the specific toxicity mechanism, explained by compensatory glycolytic activation. IC50 determination using a standard multi-well plate reader, shown that the methodology allowed to detect metabolic toxicity induced by azide, antimycin, oligomycin, rotenone and myxothiazol with high sensitivity. Suitability for high-throughput screening applications was evaluated resulting in a Z-factor > 0.5 and CV% < 20. A pilot screening allowed sensitive detection of commercial drugs that were previously withdrawn from the market due to liver/cardiac toxicity issues, such as camptothecin, ciglitazone, troglitazone, rosiglitazone, and terfenadine, in ten minutes. We envisage that the availability of this technology, based on a fluorescent genetically-encoded indicator will allow direct assessment of mitochondrial metabolism, and will make the early detection of mitochondrial toxicity in the drug development process possible, saving time and resources.

pharmacology and toxicology↗

bioRxiv2018

Cortical recruitment determines learning dynamics and strategy

Salience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we show that sounds of diverse quality, but equal intensity and perceptual detectability, can recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.

neuroscience↗