Biology subjects

Lazarte, I. P.

Publications and source records attributed to Lazarte, I. P..

4 recordsLinked to original sources

bioRxiv2024

Perinatal serotonin signalling dynamically influences the development of cortical GABAergic circuits with consequences for lifelong sensory encoding

Serotonin plays a prominent role in neurodevelopment, regulating processes from cell division to synaptic connectivity1,2. Clinical studies suggest that alterations in serotonin signalling such as genetic polymorphisms3-5 or antidepressant exposure during pregnancy6,7 are risk factors for neurodevelopmental disorders. However, an understanding of how dysfunctional neuromodulation alters systems level activity over neocortical development is lacking. Here, we use a longitudinal imaging approach to investigate how genetics, pharmacology, and aversive experience disrupt state-dependent serotonin signalling with pathological consequences for sensory processing. We find that all three factors lead to increased neocortical serotonin levels during the initial postnatal period. Genetic deletion of the serotonin transporter or antidepressant dosing results in a switch from hypo- to hyper-cortical activity that arises as a consequence of altered cortical GABAergic microcircuitry. However, the trajectories of these manipulations differ with postnatal exposure to antidepressants having effects on adult sensory encoding. The latter is not seen in the genetic model despite a similar early phenotype, and a distinct influence of maternal genotype on the development of supragranular layers. These results reveal the dynamics and critical nature of serotonin signalling during perinatal life; pharmacological targeting of which can have profound life-long consequences for cognitive development of the offspring.

neuroscience↗

bioRxiv2024

The claustrum enhances neural variability by modulating the responsiveness of the prefrontal cortex

The claustrum is recognized for its significant impact on various cognitive functions and its extensive connections with other brain regions, yet its functional role remains to be fully understood. Here, we utilized an optogenetic approach to investigate the claustrums influence on neuronal activity within the dorsal prefrontal cortex (dPFC) of mice. We conducted two-photon calcium imaging to assess dPFC cell responses during exposure to visual stimuli and widefield photostimulation of claustrum axons embedded in the dPFC. We identified three distinct subpopulations of neurons -- sensory responsive, opto responsive, and opto-boosted cells -- each exhibiting unique response dynamics to combined visual and optogenetic stimuli. Our findings reveal that stimulation of claustrum axons can normalize neuronal responsiveness, while enhancing neural variability, and significantly increasing network homogeneity. Training in a Pavlovian task showed that while enhanced variability with claustrum axon stimulation in neural responses persists, training does not further increase this variability but instead leads to greater network homogeneity. Additionally, we also performed claustrum axon silencing experiments that revealed that the claustrum may operate bidirectionally to maintain enhanced variability and homogeneity in the prefrontal cortex. These results highlight the crucial role of the claustrum in dynamically modulating dPFC activity, impacting both neuronal variability and network synchronization.

neuroscience↗

bioRxiv2024

The visuomotor transformations underlying defensive behaviors and hunting

The visual system can process diverse stimuli and make the decision to execute appropriate behaviors, but it remains unclear where and how this transformation takes place. We imaged the zebrafish visual system while larvae responded with hunting, freezing, and escape behaviors, and systematically identified visually driven neurons and behaviorally correlated sensorimotor neurons. Our analyses indicate within the optic tectum, broadly tuned sensory neurons are functionally connected to sensorimotor neurons that respond specifically during one behavior, transforming visual information into motor output. We also identified sensorimotor neurons in four other areas downstream of the tectum, and these neurons are also specific for one behavior, indicating that once the decision to behave has been made, the segregation of the pathways continues in later areas. Our findings suggest that the tectum receives visual sensory information and is responsible for selecting a single behavioral outcome, which is then relayed to downstream areas. Significance statementHere, we developed a novel visually-evoked freezing paradigm in zebrafish, and combined this with escape and hunting behaviors to ask how visual stimuli are identified and converted into different behavioral outcomes. We found that the optic tectum contains neurons that detect all three stimuli, as well as sensorimotor neurons for the three behaviors, suggesting that it is a site of sensorimotor transformation, which was supported by our analysis of correlations between the populations. The sensorimotor neurons in the tectum are highly specific for one behavior, and this segregation is maintained in the three downstream areas where we also identified sensorimotor neurons, indicating that the tectum flexibly transforms visual information into a single behavioral output.

neuroscience↗

bioRxiv2022

Single neurons and networks in the claustrum integrate input from widespread cortical sources

The claustrum is thought to be one of the most highly interconnected forebrain structures but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons to understand how the structures unique convergence of input and divergence of output support binding information streams. We found that neurons in the claustrum communicate with each other across efferent projection-defined modules which were differentially innervated by sensory and frontal cortical areas. Individual claustrum neurons were responsive to inputs from more than one cortical region in a cell-type and projection-specific manner, particularly between areas of frontal cortex. In vivo imaging of claustrum axons revealed responses to both unimodal and multimodal sensory stimuli. Finally, chronic claustrum silencing specifically reduced animals sensitivity to multimodal stimuli. These findings support the view that the claustrum is a fundamentally integrative structure, consolidating information from around the cortex and redistributing it following local computations.

neuroscience↗