Biology subjects

Cherian, C.

Publications and source records attributed to Cherian, C..

4 recordsLinked to original sources

bioRxiv2025

Neuronal normalization in monkey MT is an intensity-weighted average

Normalization is a ubiquitous neuronal computation that is important for safeguarding stimulus selectivity. However, normalization strength has been found to vary greatly across neurons. Here, we show that the normalization of responses by neurons in the macaque middle temporal visual area (MT) is profoundly affected by the receptive field responsivity at each stimulus location. An intensity-weighted normalization model, in which intensity is defined as the product of stimulus contrast and a location-specific receptive field weight, explains most of the previously observed variability in normalization across neurons. It furthermore explains systematic changes in the semi-saturation contrast of contrast response functions at different receptive field locations. Finally, intensity-weighted normalization reveals that spontaneous activity can be viewed as unknown excitatory drive that has measurable intensity and contributes to normalization equivalently to experimental stimuli.

neuroscience↗

bioRxiv2025

Sex-specific differences in the regulation and function of cellular immunity in Drosophila

Sex differences in development and physiology are prevalent in animals. One physiological system with pronounced differences between the sexes is the immune system: the immune response in humans differs between sexes and results in differential susceptibility of males and females to autoimmune diseases, malignancies, and infectious diseases. However, much remains to be discovered about the mechanisms underlying these sex-based differences in immunity. Here, we use the Drosophila hematopoietic organ, the lymph gland, as a model to investigate sex differences in cellular immunity and determine the underlying mechanisms. We find that, in line with their smaller body size, males have smaller lymph glands than females that contain fewer blood progenitors and produce less immune cells. Single cell RNA-seq analysis of the lymph gland showed that they expressed that sex determination genes and identified substantial sex-specific differences in gene expression. By manipulating the sexual identity of different cell types in the lymph gland we show that a subset of these sex differences are controlled by organ-intrinsic mechanisms involving the hematopoietic niche. Importantly, we find a differential response between males and females to changes in insulin signaling, an important regulator of the immune response in the niche. Finally, we provide evidence for differences in the cellular immune response following infection between males and females. Overall, our results provide mechanistic insight into how sex differences in immunity are established. Authors SummaryOur paper deals with a fundamental question in biology, how does the sex of an organism influence its anatomy and physiology. In particular, we focus on sex-differences in immunity and stem cell function. We establish the Drosophila larva as a model for analysing sex-based differences in cellular immunity. Cellular immunity in Drosophila is based on the production of multiple types of mature immune cells from blood progenitors and takes place in the fly hematopoietic organ, the larval lymph gland. We find that sex controls the number of various cell types in the lymph gland (progenitors, and specific varieties of mature blood cells). These sex-differences vary by cell type and change depending on whether flies are raised under homeostatic or infection conditions. We provide insight into the mechanisms that mediate these sex differences, identifying a possible role for the hematopoietic niche and insulin signaling. Taken together our work not only serves as an initial characterization of baseline sex-differences in fly hematopoiesis and cellular immunity but also identifies important areas for future exploration.

immunology↗

bioRxiv2024

A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality.

Contextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy and holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, these techniques generally require animals to be head-fixed. There are few paradigms that test contextual fear conditioning in head-fixed mice, and none where the behavioral outcome following fear conditioning is freezing, the most common measure of fear in freely moving animals. To address this gap, we developed a contextual fear conditioning paradigm in head-fixed mice using virtual reality (VR) environments. We designed an apparatus to deliver tail shocks (unconditioned stimulus, US) while mice navigated a VR environment (conditioned stimulus, CS). The acquisition of contextual fear was tested when the mice were reintroduced to the shock-paired VR environment the following day. We tested three different versions of this paradigm and, in all of them, observed an increased conditioned fear response characterized by increased freezing behavior. This was especially prominent during the first trial in the shock-paired VR environment, compared to a neutral environment where the mice received no shocks. Our results demonstrate that head-fixed mice can be fear conditioned in VR, discriminate between a feared and neutral VR context, and display freezing as a conditioned response, similar to freely behaving animals. Furthermore, using a two-photon microscope, we imaged from large populations of hippocampal CA1 neurons before, during, and following contextual fear conditioning. Our findings reconfirmed those from the literature on freely moving animals, showing that CA1 place cells undergo remapping and show narrower place fields following fear conditioning. Our approach offers new opportunities to study the neural mechanisms underlying the formation, recall, and extinction of contextual fear memories. As the head-fixed preparation is compatible with multi-photon microscopy and holographic stimulation, it enables long-term tracking and manipulation of cells throughout distinct memory stages and provides subcellular resolution for investigating axonal, dendritic, and synaptic dynamics in real-time.

animal behavior and cognition↗

bioRxiv2020

Changing reward expectation transforms spatial encoding and retrieval in the hippocampus

Internal states of reward expectation play a central role in influencing the strength of spatial memories. At the cellular level, spatial memories are represented through the firing dynamics of hippocampal place cells. However, it remains unclear how internal states of reward expectation influence place cell dynamics and exert their effects on spatial memories. Here we show that when reward expectation is altered, the same environment becomes encoded by a distinct ensemble of place cells at all locations. Further, when reward expectation is high versus low, place cells demonstrate enhanced reliability during navigation and greater stability across days at all locations within the environment. These findings reveal that when rewards are expected, neuromodulatory circuits that represent internal reward expectation support and strengthen the encoding and retrieval of spatial information by place cells at all locations that lead to reward. This enhanced spatial memory can be used to guide future decisions about which locations are most likely to lead to rewards that are crucial for survival.

neuroscience↗