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Unveiling Hidden Neural Codes: SIMPL – A Scalable and Fast Approach for Optimizing Latent Variables and Tuning Curves in Neural Population Data

Dr. Rishabh Pathak
This research paper presents SIMPL (Scalable Iterative Maximization of Population-coded Latents), a novel, computationally efficient algorithm designed to refine the estimation of latent variables and tuning curves from neural population activity. Latent variables in neural data represent essential low-dimensional quantities encoding behavioral or cognitive states, which neuroscientists seek to identify to understand brain computations better. Background and Motivation Traditional approaches commonly assume the observed behavioral variable as the latent neural code. However, this assumption can lead to inaccuracies because neural activity sometimes encodes internal cognitive states differing subtly from observable behavior (e.g., anticipation, mental simulation). Existing latent variable models face challenges such as high computational cost, poor scalability to large datasets, limited expressiveness of tuning models, or difficulties interpreting complex neural network-based functio...
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Dynamics Interactions Underpinning Secretory Vesicle Fusion

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Dr. Rishabh Pathak

The dynamics of interactions underpinning secretory vesicle fusion are crucial for neurotransmitter release and synaptic communication. Here is an overview of the key molecular interactions involved in the process of secretory vesicle fusion at the synapse:


1.      SNARE Complex Formation:

o SNARE Proteins: Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, including syntaxin, synaptobrevin (VAMP), and SNAP-25, play a central role in mediating membrane fusion.

o    Complex Formation: SNARE proteins from the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs) form a stable SNARE complex, bringing the vesicle close to the plasma membrane for fusion.

2.     Synaptotagmin Interaction with Calcium:

o    Calcium Sensor: Synaptotagmin, a calcium-binding protein located on the vesicle membrane, senses the increase in intracellular calcium levels upon neuronal depolarization.

o Calcium Binding: Calcium binding to synaptotagmin triggers conformational changes that promote the interaction between the vesicle and the plasma membrane, facilitating membrane fusion.

3.     Complexin Regulation:

o  Complexin Binding: Complexin is a protein that binds to the SNARE complex and regulates the timing of membrane fusion by preventing premature fusion and ensuring synchronized release of neurotransmitters.

o    Fusion Promotion: Complexin interacts with the SNARE complex to facilitate the final steps of membrane fusion, leading to the release of neurotransmitters into the synaptic cleft.

4.    Munc18-1 and Munc13 Interaction:

o    Munc18-1: Munc18-1 is a protein that interacts with syntaxin and regulates SNARE complex assembly and vesicle fusion.

o Munc13: Munc13 is involved in priming vesicles for fusion by promoting the transition of vesicles to a fusion-ready state through interactions with SNARE proteins and other regulatory factors.

5.     Rab Proteins and Membrane Trafficking:

o    Rab GTPases: Rab proteins regulate vesicle trafficking, docking, and fusion by coordinating membrane dynamics and vesicle transport to specific subcellular locations.

o Membrane Fusion Regulation: Rab GTPases interact with tethering factors, SNARE proteins, and other regulatory molecules to orchestrate the fusion of secretory vesicles with the target membrane.

Understanding the intricate molecular interactions underlying secretory vesicle fusion is essential for elucidating the mechanisms of neurotransmitter release at synapses and synaptic communication. Dysregulation of these interactions can lead to synaptic dysfunction and neurological disorders characterized by impaired neurotransmission. Studying the dynamics of these interactions provides valuable insights into the fundamental processes governing synaptic function and offers potential targets for therapeutic interventions aimed at restoring proper synaptic vesicle fusion and neurotransmitter release in the brain.

 

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