Biology subjects

de Hoz, L.

Publications and source records attributed to de Hoz, L..

7 recordsLinked to original sources

bioRxiv2022

Coding of unsupervised predictable sound-context associations in the auditory midbrain

Our environment is made of a myriad of stimuli present in combinations often patterned in predictable ways. For example, there is a strong association between where we are and the sounds we hear. Like so many environmental patterns, sound-context associations are learned implicitly, in an unsupervised manner, and are highly informative and predictive of normality. Yet, we know little about where and how unsupervised sound-context associations are coded in the brain. Here we measured plasticity in the auditory midbrain of mice living over days in a naturalistic environment designed to present sound-context associations with different degrees of predictability. Plasticity in the auditory midbrain, a hub of auditory input and multimodal feedback, developed over days and reflected learning of contextual information in a manner that depended on the predictability of the sound-context association and not on reinforcement. Plasticity took the form of broad frequency shifts in tuning in auditory midbrain neurons. These shifts were paralleled by an increase in response gain and correlated with an increase in neuronal frequency discrimination. Thus, the auditory midbrain codes for unsupervised predictable sound-context associations, revealing a subcortical engagement in the detection of contextual sounds. This detection might facilitate the processing of behaviorally relevant foreground information described to occur in cortical auditory structures.

neuroscience↗

bioRxiv2022

Prior unsupervised experience leads to long lasting effects in sensory gating during discrimination learning

As the animal moves in its environment, the brain detects and learns the structure of the surrounding stimuli, independently of the immediate relevance this has for the animal. This experience influences subsequent learning in a manner quantified using paradigms such as latent inhibition or stimulus preconditioning, which measure the effect that unsupervised (not-reinforced) learning has on subsequent reinforced learning. Despite our understanding of the behavioural consequences of prior neutral experience, there is little understanding about the influence of this previous experience on neuronal plasticity. Using latent inhibition, we have shown in mice that learning a two tone discrimination is slower in mice that have had previous neutral exposure to the same or similar tones (<2/3 octave away). Neutral exposure thus elicits profound changes in the brain that influence subsequent learning. To study how previous experience influences experience-dependent plasticity, and better understand the interactions between experience, learning, and plasticity, we recorded sound evoked responses in the auditory cortex of exposed and trained mice. We studied both changes in response magnitude and changes in sensory dynamics, and related both to the differential behavioral effects of different pre-exposure conditions. Here we describe the neuronal changes that paralleled the behavioral findings. We found that discrimination learning led to stronger initial sound-evoked responses and a long-lasting increase in response adaptation and an increase. The first effect was delayed in animals that showed latent inhibition, paralleling behavioural learning. Overall our data reveal that slow changes in behaviour that accompanied learning, paralleled the slow dynamics of experience-dependent plasticity in auditory cortex.

neuroscience↗

bioRxiv2021

Sound disrupts sleep-associated brain oscillations inrodents according to its meaning

Sleep is essential but poses a risk to the animal. Filtering acoustic information according to its relevance, a process generally known as sensory gating, is crucial during sleep to ensure a balance between rest and danger detection. The mechanisms of this sensory gating and its specificity are not understood. Here, we tested the effect that sounds of different meaning had on sleep-associated ongoing oscillations. We recorded EEG and EMG from mice during rapid-eye movement (REM) and non-REM (NREM) sleep while presenting sounds with or without behavioural relevance. We found that sound presentation per se, in the form of an unfamiliar neutral sound, elicited a weak or no change in the sleep-dependent EEG power during NREM and REM sleep. In contrast, the presentation of a sound previously conditioned in an aversive task, elicited a clear and fast decrease in the sleep-dependent EEG power during both sleep phases, suggesting a transition to lighter sleep without awakening. The observed changes generally weakened over training days and were not present in animals that failed to learn. Interestingly, the effect could be generalized to unfamiliar neutral sounds if presented following conditioned training, an effect that depended on sleep phase and sound type. The data demonstrate that sounds are differentially gated during sleep depending on their meaning and that this process is reflected in disruption of sleep-associated brain oscillations without an effect on behavioural arousal.

neuroscience↗

bioRxiv2021

Natural sound characteristics explain perceptual categorization

As we interact with our surroundings, we encounter the same or similar objects from different perspectives and are compelled to generalize. For example, we recognize dog barks as a distinct class of sound, despite the variety of individual barks. While we have some understanding of how generalization is done along a single stimulus dimension, such as frequency or color, natural stimuli are identifiable by a combination of dimensions. To understand perception, measuring the interaction across stimulus dimensions is essential. For example, when identifying a sound, does our brain focus on a specific dimension or a combination, such as its frequency and duration? Furthermore, does the relative relevance of each dimension reflect its contribution to the natural sensory environment? Using a 2- dimension discrimination task for mice we tested untrained generalization across several pairs of auditory dimensions in a naturalistic and automatized behavioral paradigm. We uncovered a perceptual hierarchy over the tested dimensions that was dominated by the sounds spectral composition. This hierarchy could reflect the relevance of the different dimensions in natural stimuli and their potentially associated differential shaping of neuronal tuning. Mice could learn to pay more attention to dimensions low in the hierarchy, but this learning was more rigid and did not generalize as flexibly. Stimuli are thus not perceived as a whole but as a combination of their features, each of which weights differently on the dentification of the stimulus according to an established hierarchy.

neuroscience↗

bioRxiv2019

A role of oligodendrocytes in information processing independent of conduction velocity

Myelinating oligodendrocytes enable fast impulse propagation along axons as revealed through studies of homogeneously myelinated white matter tracts. However, gray matter myelination patterns are different, with sparsely myelinated sections leaving large portions of the axons naked. The consequences of this patchy myelination for oligodendrocyte function are not understood but suggest other roles in information processing beyond the regulation of axonal conduction velocity. Here, we analyzed the contribution of myelin to auditory information processing using paradigms that are good predictors of speech understanding in humans. We compared mice with different degrees of dysmyelination using acute cortical multiunit recordings in combination with behavioral readouts. We identified complex alterations of neuronal responses that reflect fatigue and temporal acuity deficits. Partially discriminable but overall similar deficits were observed in mice with oligodendrocytes that can myelinate but cannot fully support axons metabolically. Thus, myelination contributes to sustained stimulus perception in temporally complex paradigms, revealing a role of oligodendrocytes in the CNS beyond the increase of axonal conduction velocity.

neuroscience↗

bioRxiv2019

jULIEs: extracellular probes for recordings and stimulation in the structurally and functionally intact mouse brain

High signal-to-noise, scalable and minimally invasive recording and stimulation of the nervous system in intact animals is of fundamental importance to advance the understanding of brain function. Extracellular electrodes are among the most powerful tools capable of interfacing with large neuronal populations1-3. Neuronal tissue damage remains a major limiting factor in scaling electrode arrays, and has been found to correlate with electrode diameter across different electrode materials, such as microfabricated Michigan and Utah-style arrays4, MEMS and microsystems5, soft polymer or tungsten electrodes6 and Parylene C probes7. Small diameter ultramicroelectrodes (UMEs), while highly desirable, pose significant technical challenges such as reaching sufficient electrolyte-electrode coupling and limiting stray signal loss. To overcome these challenges, we have designed juxtacellular Ultra-Low Impedance Electrodes (jULIEs), a scalable technique for achieving high signal-to-noise electrical recordings as well as stimulation with UMEs. jULIEs are metal-glass composite UMEs thermally drawn to outer diameters (OD) of <25 {micro}m, with metal core diameters (ID) of as little as 1 {micro}m. We introduce a two-step electrochemical modification strategy that reduces UME coupling impedances by two orders of magnitude. Modifications enabled high signal-to-noise neural recordings in vivo through wires with micrometer scale core diameters. Histological and imaging experiments indicated that local vascular damage is minimal. Spikes reached amplitudes over 1 mV in vivo, indicating that recordings are possible in close proximity to intact neurons. Recording sites can be arranged in arbitrary patterns tailored to various neuroanatomical target structures and allowing parallel penetrations. jULIEs thus represent a versatile platform that allows for reliable recording and manipulation of neural activity in any areas of the functionally intact mammalian brain.

neuroscience↗

bioRxiv2019

Physiological and pathophysiological homeostasis of astroglial channel proteins by Nedd4-2

Nedd4-2 is an E3 ubiquitin ligase, missense mutation of which is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of {gamma}-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity, and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy.\n\nCONDENSED TITLEUbiquitination of Astrocytic Channels by Nedd4-2\n\nSUMMARYUbiquitination is a key regulatory machinery for protein expression. Our present work provides evidence that astrocytic ion channel proteostasis coordinated by an E3 ubiquitin ligase Nedd4-2 is of particular importance for the maintenance of neuronal network activity.

neuroscience↗