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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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The Polysialylation Of NCAM

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Dr. Rishabh Pathak

Polysialylation of NCAM refers to the post-translational modification of the Neural Cell Adhesion Molecule (NCAM) with polysialic acid chains. Here is an overview of polysialylation of NCAM:

1.      Polysialic Acid (PSA):

o  Polysialic acid is a linear homopolymer of α-2,8-linked sialic acid residues.

o    PSA is a large, negatively charged carbohydrate polymer that can be attached to glycoproteins, with NCAM being one of the major carriers of polysialic acid in the nervous system.

2.     Function of Polysialylation:

o    Regulation of Cell Adhesion: Polysialylation of NCAM reduces its adhesive properties, leading to decreased cell-cell adhesion and increased cell motility.

o Neuronal Plasticity: Polysialylation of NCAM is involved in modulating neuronal plasticity, axon guidance, and synaptic remodeling during development and in response to environmental cues.

o    Neurite Outgrowth: PSA-NCAM promotes neurite outgrowth by reducing cell adhesion, allowing for increased exploratory behavior of growth cones and facilitating axon pathfinding.

3.     Developmental Role:

o Neural Development: Polysialylation of NCAM is particularly important during neural development, where it regulates processes such as neuronal migration, axon guidance, and synaptogenesis.

o    Plasticity and Learning: The dynamic regulation of polysialylation of NCAM is associated with synaptic plasticity, learning, and memory formation in the brain.

4.    Regulation of Polysialylation:

o    Enzymatic Modification: Polysialylation of NCAM is catalyzed by two polysialyltransferases, ST8SiaII and ST8SiaIV, which add polysialic acid chains to specific sites on NCAM.

o Developmental Regulation: The expression and activity of polysialyltransferases are tightly regulated during development and can be influenced by various extracellular signals and neuronal activity.

5.     Functional Implications:

o  Disease Associations: Dysregulation of polysialylation of NCAM has been implicated in neurodevelopmental disorders, neurodegenerative diseases, and psychiatric conditions.

o  Therapeutic Potential: Modulation of polysialylation of NCAM represents a potential therapeutic target for promoting neural regeneration, enhancing synaptic plasticity, and treating neurological disorders.

In summary, polysialylation of NCAM plays a critical role in regulating cell adhesion, neuronal plasticity, and neural development by modulating the adhesive properties of NCAM and influencing processes such as neurite outgrowth, axon guidance, and synaptic remodeling. The dynamic regulation of polysialylation of NCAM contributes to the functional diversity of NCAM in the nervous system and its involvement in various physiological and pathological conditions.

 

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