@article {140649, title = {Challenges and opportunities for discovering the biology of rare genetic diseases of the brain.}, journal = {J Biosci}, volume = {49}, year = {2024}, month = {2024}, abstract = {

Diseases of the human nervous system are an important cause of morbidity and mortality worldwide. These disorders arise out of multiple aetiologies of which rare genetic mutations in genes vital to nervous system development and function are an important cause. The diagnosis of such rare disorders is challenging due to the close overlap of clinical presentations with other diseases that are not of genetic origin. Further, understanding the mechanisms by which mutations lead to altered brain structure and function is also challenging, given that the brain is not readily accessible for tissue biopsy. However, recent developments in modern technologies have opened up new opportunities for the analysis of rare genetic disorders of the brain. In this review, we discuss these developments and strategies by which they can be applied effectively for better understanding of rare diseases of the brain. This will lead to the development of new clinical strategies to manage brain disorders.

}, keywords = {Biology, Brain, Humans, Mutation, Rare Diseases}, issn = {0973-7138}, author = {Raghu, Padinjat and Sharma, Yojet and Suseela Devi, Aswathy Bhuvanendran Nair and Krishnan, Harini} } @article {1016, title = {Neighborhood matters: divergent patterns of stress-induced plasticity across the brain.}, journal = {Nat Neurosci}, volume = {18}, year = {2015}, month = {2015 Oct}, pages = {1364-75}, abstract = {

The fact that exposure to severe stress leads to the development of psychiatric disorders serves as the basic rationale for animal models of stress disorders. Clinical and neuroimaging studies have shown that three brain areas involved in learning and memory--the hippocampus, amygdala and prefrontal cortex--undergo distinct structural and functional changes in individuals with stress disorders. These findings from patient studies pose several challenges for animal models of stress disorders. For instance, why does stress impair cognitive function, yet enhance fear and anxiety? Can the same stressful experience elicit contrasting patterns of plasticity in the hippocampus, amygdala and prefrontal cortex? How does even a brief exposure to traumatic stress lead to long-lasting behavioral abnormalities? Thus, animal models of stress disorders must not only capture the unique spatio-temporal features of structural and functional alterations in these brain areas, but must also provide insights into the underlying neuronal plasticity mechanisms. This Review will address some of these key questions by describing findings from animal models on how stress-induced plasticity varies across different brain regions and thereby gives rise to the debilitating emotional and cognitive symptoms of stress-related psychiatric disorders.

}, keywords = {Animals, Brain, Humans, Neuronal Plasticity, Stress, Psychological}, issn = {1546-1726}, doi = {10.1038/nn.4115}, author = {Chattarji, Sumantra and Tomar, Anupratap and Suvrathan, Aparna and Ghosh, Supriya and Rahman, Mohammed Mostafizur} } @article {1011, title = {Sloppiness in spontaneously active neuronal networks.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Jun 3}, pages = {8480-92}, abstract = {

Various plasticity mechanisms, including experience-dependent, spontaneous, as well as homeostatic ones, continuously remodel neural circuits. Yet, despite fluctuations in the properties of single neurons and synapses, the behavior and function of neuronal assemblies are generally found to be very stable over time. This raises the important question of how plasticity is coordinated across the network. To address this, we investigated the stability of network activity in cultured rat hippocampal neurons recorded with high-density multielectrode arrays over several days. We used parametric models to characterize multineuron activity patterns and analyzed their sensitivity to changes. We found that the models exhibited sloppiness, a property where the model behavior is insensitive to changes in many parameter combinations, but very sensitive to a few. The activity of neurons with sloppy parameters showed faster and larger fluctuations than the activity of a small subset of neurons associated with sensitive parameters. Furthermore, parameter sensitivity was highly correlated with firing rates. Finally, we tested our observations from cell cultures on an in vivo recording from monkey visual cortex and we confirm that spontaneous cortical activity also shows hallmarks of sloppy behavior and firing rate dependence. Our findings suggest that a small subnetwork of highly active and stable neurons supports group stability, and that this endows neuronal networks with the flexibility to continuously remodel without compromising stability and function.

}, keywords = {Action Potentials, Animals, Brain, Cells, Cultured, Electric Stimulation, Embryo, Mammalian, Entropy, Models, Neurological, Nerve Net, Neural Pathways, Neurons, Rats, Synapses, Visual Cortex}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.4421-14.2015}, author = {Panas, Dagmara and Amin, Hayder and Maccione, Alessandro and Muthmann, Oliver and van Rossum, Mark and Berdondini, Luca and Hennig, Matthias H} }