Biology subjects

Gosselin, E.

Publications and source records attributed to Gosselin, E..

4 recordsLinked to original sources

bioRxiv2025

Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood brain barrier disruption

Focal stroke leads to complex changes in the cerebral microcirculation in surviving brain tissues that strongly influence recovery. Plasminogen activator inhibitor-1 (PAI-1; encoded by Serpine1) is highly upregulated in endothelial cells after stroke. Since the primary function of PAI-1 is to inhibit fibrin clot breakdown, we hypothesized that blocking this pathway would be beneficial for recovery since it is expected to increase capillary blood flow after stroke. Using longitudinal in vivo imaging in mice subjected to ischemic stroke, we unexpectedly found that knockdown of Serpine1 in brain endothelial cells leads to a long-lasting reduction in peri-infarct capillary width, red blood cell velocity and flux. Conversely, stimulating this pathway in naive mice increased capillary width and blood flow. Lowered peri-infarct blood flow in Serpine1 knockdown mice attenuated deleterious blood brain barrier disruption and pro-inflammatory gene expression. Serpine1 knockdown improved the progressive recovery of sensory evoked cortical responses, as well as cognitive and sensorimotor function. These findings challenge the assumption that increased blood flow after stroke is better for recovery and reveal that carefully tuning flow, rather than maximizing it, may be optimal. Further our data highlight the therapeutic potential of targeting endothelial Serpine1/PAI-1 signalling in promoting stroke recovery.

neuroscience↗

bioRxiv2025

Sound offset responses become highly informative in the auditory cortex

The entire auditory system downstream of the cochlea features pronounced offset responses, which follow the termination of sounds. Because of their ubiquity, it is still an unsolved question whether offset responses are generated early in the auditory system and then propagated or recomputed at each processing stage. Here, we analysed large-scale sound responses datasets acquired in the cochlear nucleus, inferior colliculus, medial geniculate nucleus and auditory cortex of awake mice. All brain regions showed a significant proportion of offset responses often combined with onset and sustained responses in the same neuron. However, using population activity decoders, we observed that neural representations after the sound offset show a three-fold increase in sound encoding accuracy in the cortex relative to subcortical areas. This result indicates that cortical offsets encode a more precise short-term memory of the elapsed sound than subcortical offsets and that they likely result from specific computational steps. Key points summaryO_LIOffset responses are found throughout the central auditory system C_LIO_LIOffset responses are often combined to sustained and onset responses at all central auditory system stages C_LIO_LIOffset responses provide richer information about elapsed sounds in the auditory cortex C_LI

neuroscience↗

bioRxiv2025

Feature-dependent decorrelation of sound representations across the auditory pathway

AbstractEarly studies on orientation selectivity in the visual cortex have suggested that sensory systems generate new feature representations at specific processing stages. Many observations challenge this view, but in the absence of systematic, multistage measurements, the logic of how feature tuning emerges remains elusive. Here, using a generic approach based on representational similarity analysis with a noise-corrected population metric, we demonstrate in the mouse auditory system that feature representations evolve gradually with, in some cases, major, feature-specific improvements at particular stages. We observe that single frequency tuning is already fully developed in the cochlear nucleus, the first stage of processing, while tuning to higher-order features improves up to the auditory cortex, with major steps in the inferior colliculus for amplitude modulation frequency or noise bandwidth tuning and in the cortex for frequency modulation direction and for complex sound identity or direction. Moreover, we observe that intensity tuning is established in a feature-dependent manner, earlier for pure frequencies than for more complex sounds. This indicates that auditory feature computations are a mix of stepwise and gradual processes which together contribute to decorrelate sound representations.

neuroscience↗

bioRxiv2024

Massive perturbation of sound representations by anesthesia in the auditory brainstem

Anesthesia modifies sensory representations in the thalamo-cortical circuit, but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation in anesthesia is not possible based on awake activity. However, population level parameters, such as average tuning strength and population decoding accuracy are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing. TeaserAnesthesia compromises the normal transmission of sensory information as early as the first relay in the auditory system.

neuroscience↗