Biology subjects

Khan, B.

Publications and source records attributed to Khan, B..

4 recordsLinked to original sources

bioRxiv2024

Integration of binocular vision and motor state to promote prey pursuit

Most animals with two eyes combine the inputs to achieve binocular vision, which can serve numerous functions, and is particularly useful in hunting prey. However, the mechanisms by which visual information from the two eyes are combined remain largely unknown. Here, we designed a device to reversibly occlude the eyes of a head-fixed zebrafish larva, and used large-scale volumetric two-photon imaging to identify binocular neurons that respond to prey stimuli. We found these binocular prey-responsive neurons (bino-PRNs) were primarily located in three areas, the pretectum, thalamus, and nucleus isthmi. We then characterized the bino-PRNs functional properties, and found that their left and right eye receptive fields are offset to varying degrees, which would correspond to objects at naturalistic hunting distances for a larva with converged eyes. We also found that bino-PRNs have a significantly greater response in hunting trials, which could be the result of an eye convergence-related corollary discharge. We then optogenetically induced prey capture eye and tail movements, and found that this hunting command activates prey responsive neurons in the pretectum, thalamus, and nucleus isthmi. These findings indicate that bino-PRNs receive visual and motor input that would allow them to encode prey position in three dimensions.

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↗

bioRxiv2024

Sorafenib induces muscle wasting by disrupting the activity of distinct chromatin regulators

Adverse effects of chemotherapies can outweigh the benefits in cancer patients. Various chemotherapeutics are linked to muscle wasting or cachexia, drastically reducing the chance of survivability of cancer patients. Insights into the molecular basis of chemotherapy-induced cachexia is an unmet need to improve the treatment strategies. Here, we investigated the tyrosine kinase inhibitor class of chemotherapeutic agents for their effects on muscle function. Sorafenib, but not Nilotinib and Imatinib, triggered cachexia. System-wide transcriptome and proteome analyses revealed that Sorafenib alters the global transcriptional program and proteostasis in muscle cells. Mechanistically, Sorafenib treatment reduced active epigenetic mark H3K4 methylation on distinct muscle-specific genes due to the defective chromatin association of SET1/A, a catalytic component of the SET1/MLL complex. It favored transcriptionally incompetent chromatin, characterized by diminished association with RNA polymerase II. The transcriptional reorientation led to disrupted sarcomere organization, calcium homeostasis, and mitochondrial respiration. Consequently, the contractile ability of muscle cells was severely compromised. Collectively, we identified an unanticipated transcriptional mechanism underlying Sorafenib-induced cachexia. Our findings hold the potential to strategize therapy regimens to minimize chemotherapy-induced cachexia and improve treatment outcomes.

cell biology↗

bioRxiv2020

Whole-brain mapping of monosynaptic inputs to midbrain cholinergic neurons

The cholinergic midbrain is involved in a wide range of motor and cognitive processes. Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental nucleus (LDT) send long-ranging axonal projections that target sensorimotor and limbic areas in the thalamus, the dopaminergic midbrain and the striatal complex following a topographical gradient, where they influence a range of functions including attention, reinforcement learning and action-selection. Nevertheless, a comprehensive examination of the afferents to PPN and LDT cholinergic neurons is still lacking, partly due to the neurochemical heterogeneity of this region. Here we characterize the whole-brain input connectome to cholinergic neurons across distinct functional domains (i.e. PPN vs LDT) using conditional transsynaptic retrograde labeling in ChAT::Cre male and female rats. The quantification of input neurons revealed that both PPN and LDT receive similar substantial inputs from the superior colliculus and the output of the basal ganglia (i.e. substantia nigra pars reticulata). In addition, we found that PPN cholinergic neurons receive preferential inputs from basal ganglia structures than from the cortex, whereas LDT cholinergic neurons receive preferential inputs from cortical areas. Our results provide the first characterization of inputs to PPN and LDT cholinergic neurons. The differences in afferents to each cholinergic structure support their differential roles in behavior. Significance statementAcetylcholine is a widespread neuromodulator that regulates a wide variety of functions including learning, goal-directed behavior and execution of movements. In this study we characterized the distribution of presynaptic neurons that modulate the activity of functionally distinct midbrain cholinergic neurons located in the pedunculopontine nucleus (PPN) and the laterodorsal tegmental nucleus (LDT) by using a transsynaptic, modified-rabies virus strategy. We reveal that input neurons are widely distributed throughout the brain but segregated into specific functional domains. Motor related areas innervate preferentially the PPN, whereas limbic related areas preferentially innervate the LDT. Our results suggest that input neurons located along distinct functional domains have differential impact over cholinergic midbrain regions.

neuroscience↗