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Farjami, S.

Publications and source records attributed to Farjami, S..

4 recordsLinked to original sources

Beyond Locomotion: How Specialized Motor Rhythms Enable Vertebrate Escape from Capture

Escape behaviors following capture are crucial for survival, yet their underlying neurobiological mechanisms remain poorly understood. We investigated how Xenopus laevis tadpoles use struggling movements to escape head restraint. High-speed video tracking revealed a stereotyped sequence of body flexions with distinct kinematics during capture and release. We further recorded motoneuron and motor nerve activity along the body axis during fictive struggling to reconstruct biologically realistic struggling commands, to drive the movement of a biomechanically detailed tadpole model. Simulations showed that struggling - characterized by long-duration, low-frequency, caudorostral muscle activation - was optimized to generate escape forces. Notably, hydrodynamic thrust alone proved insufficient for release. However, direct mechanical interactions between the tadpoles body and the restraining object generated additional reactive forces that facilitated escape. These findings demonstrate how animals use coordinated motor outputs and body mechanics to interact with environment to generate maximal freeing forces as the fundamental escape strategy.

neuroscience↗

Amygdala GABA Neurons: Gatekeepers of Stress and Reproduction

Stress can disrupt menstrual cycles, cause infertility, and lead to other reproductive disorders. The posterodorsal medial amygdala (MePD) processes stress signals and regulates the gonadotropin-releasing hormone (GnRH) pulse generator through GABAergic inhibitory projections to the hypothalamus. However, how stress is processed in the MePD - especially involving its dense GABA and Urocortin-3 (UCN3) neurons - remains poorly understood. In this study, we combine in vivo GRadient-INdex (GRIN) lens mini-endoscopic calcium imaging (to track neuronal activity), optogenetics, clustering analysis, and computational modeling to investigate the MePD circuitry. Our findings reveal two anti-correlated GABA subpopulations in the MePD that dictate responses to both UCN3 neuron stimulation and restraint stress. Our computational modeling suggests that mutual inhibition between these GABA groups drives the anti-correlated activity and predicts how these interactions shape downstream responses to stimulation of GABA and UCN3 neurons. We test these predictions using optogenetics and confirm that GABA neurons are critical for the transmission of UCN3 signals to regulate luteinizing hormone (LH) pulse frequency. Our study is the first to show how GABA neurons in the amygdala mediate stress effects on reproductive health, uncovering key neural mechanisms linking emotional and reproductive functions.

physiology↗

Decoding the relative contributions of extrinsic and intrinsic mechanisms in mediating heterogeneous spiking activities of sensory neurons in vivo using computational modeling

Neurons ubiquitously display heterogeneities in spiking activity even within a given cell type. To date, the relative contributions of extrinsic mechanisms (e.g., synaptic bombardment) and intrinsic mechanisms (e.g., conductances, cell morphology) towards determining spiking activity remain poorly understood. Here we address this important question using a novel approach that combines biophysical techniques, in which extracellular in vivo recordings of electrosensory pyramidal cells within weakly electric fish, are combined with computational modeling. Specifically, by varying parameters, a conductance-based computational model successfully reproduced the highly heterogeneous spiking activities seen experimentally. Model parameters that varied the most were then used to gauge the relative contributions of extrinsic vs. intrinsic mechanisms. Overall, extrinsic synaptic input was predicted to be the main factor accounting for spiking heterogeneities. We tested this prediction experimentally by performing two different manipulations: i) pharmacologically inactivating feedback; ii) applying the neuromodulator serotonin. Our model predicted that feedback inactivation should reduce while serotonin application should increase spiking heterogeneities. Experiments corroborated these predictions. Importantly, for serotonin application, increased heterogeneity occurred despite a strong reduction in intrinsic membrane conductance, further demonstrating that extrinsic synaptic input is the primary determinant of spiking heterogeneities in vivo. Taken together, our results demonstrate that devising a computational model to capture spiking heterogeneities in vivo and assessing which parameters are responsible can successfully determine the relative contributions of extrinsic vs. intrinsic inputs. We expect this approach to be generalizable to other systems and species.

neuroscience↗

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddingtons epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

developmental biology↗