@article {153341, title = {Discriminating neural ensemble patterns through dendritic computations in randomly connected feedforward networks.}, journal = {Elife}, volume = {13}, year = {2025}, month = {2025 Jan 24}, abstract = {

Co-active or temporally ordered neural ensembles are a signature of salient sensory, motor, and cognitive events. Local convergence of such patterned activity as synaptic clusters on dendrites could help single neurons harness the potential of dendritic nonlinearities to decode neural activity patterns. We combined theory and simulations to assess the likelihood of whether projections from neural ensembles could converge onto synaptic clusters even in networks with random connectivity. Using rat hippocampal and cortical network statistics, we show that clustered convergence of axons from three to four different co-active ensembles is likely even in randomly connected networks, leading to representation of arbitrary input combinations in at least 10 target neurons in a 100,000 population. In the presence of larger ensembles, spatiotemporally ordered convergence of three to five axons from temporally ordered ensembles is also likely. These active clusters result in higher neuronal activation in the presence of strong dendritic nonlinearities and low background activity. We mathematically and computationally demonstrate a tight interplay between network connectivity, spatiotemporal scales of subcellular electrical and chemical mechanisms, dendritic nonlinearities, and uncorrelated background activity. We suggest that dendritic clustered and sequence computation is pervasive, but its expression as somatic selectivity requires confluence of physiology, background activity, and connectomics.

}, keywords = {Animals, Axons, Computer Simulation, Dendrites, Hippocampus, Models, Neurological, Nerve Net, Neurons, Rats, Synapses}, issn = {2050-084X}, doi = {10.7554/eLife.100664}, author = {Bhanu Priya Somashekar and Upinder Singh Bhalla} } @article {880, title = {Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Jan 7}, pages = {325-38}, abstract = {

Neurodevelopmental disorders arise from single or multiple gene defects. However, the way multiple loci interact to modify phenotypic outcomes remains poorly understood. Here, we studied phenotypes associated with mutations in the schizophrenia susceptibility gene dysbindin (dysb), in isolation or in combination with null alleles in the dysb network component Blos1. In humans, the Blos1 ortholog Bloc1s1 encodes a polypeptide that assembles, with dysbindin, into the octameric BLOC-1 complex. We biochemically confirmed BLOC-1 presence in Drosophila neurons, and measured synaptic output and complex adaptive behavior in response to BLOC-1 perturbation. Homozygous loss-of-function alleles of dysb, Blos1, or compound heterozygotes of these alleles impaired neurotransmitter release, synapse morphology, and homeostatic plasticity at the larval neuromuscular junction, and impaired olfactory habituation. This multiparameter assessment indicated that phenotypes were differentially sensitive to genetic dosages of loss-of-function BLOC-1 alleles. Our findings suggest that modification of a second genetic locus in a defined neurodevelopmental regulatory network does not follow a strict additive genetic inheritance, but rather, precise stoichiometry within the network determines phenotypic outcomes.

}, keywords = {Animals, Animals, Genetically Modified, Carrier Proteins, Drosophila, Drosophila Proteins, Dystrophin-Associated Proteins, Female, Gene Dosage, Nerve Net, Neuronal Plasticity, Schizophrenia, Synapses, Synaptic Transmission}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3542-14.2015}, author = {Mullin, Ariana P and Sadanandappa, Madhumala K and Ma, Wenpei and Dickman, Dion K and VijayRaghavan, Krishnaswamy and Ramaswami, Mani and Sanyal, Subhabrata and Faundez, Victor} } @article {734, title = {Neural control of wing coordination in flies.}, journal = {Curr Biol}, volume = {25}, year = {2015}, month = {2015 Jan 5}, pages = {80-6}, abstract = {

At the onset of each flight bout in flies, neural circuits in the CNS must rapidly integrate multimodal sensory stimuli and synchronously engage hinges of the left and right wings for coordinated wing movements. Whereas anatomical and physiological investigations of flight have been conducted on larger flies, molecular genetic studies in Drosophila have helped identify neurons that mediate various levels of flight control. However, neurons that might mediate bilateral coordination of wing movements to precisely synchronize left and right wing engagement at flight onset and maintain their movement in perfect coordination at rapid frequencies during flight maneuvers remain largely unexplored. Wing coordination could be directly modulated via bilateral sensory inputs to motoneurons of steering muscles and/or through central interneurons. Using a Ca(2+)-activity-based GFP reporter, we identified three flight-activated central dopaminergic interneurons in the ventral ganglion, which connect to and activate motoneurons that innervate a pair of direct-steering flight muscles. The activation of these newly identified dopaminergic interneurons is context specific. Whereas bilateral wing engagement for flight requires these neurons, they do not control unilateral wing extension during courtship. Thus, independent central circuits function in the context of different natural behaviors to control the motor circuit for Drosophila wing movement.

}, keywords = {Animals, Central Nervous System, Dopaminergic Neurons, Drosophila, Flight, Animal, Genes, Reporter, Male, Synapses, Wings, Animal}, issn = {1879-0445}, doi = {10.1016/j.cub.2014.10.069}, author = {Sadaf, Sufia and Reddy, O Venkateswara and Sane, Sanjay P and Hasan, Gaiti} } @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} }