Biology subjects

Basak, R.

Publications and source records attributed to Basak, R..

5 recordsLinked to original sources

bioRxiv2022

Cross-strata co-occurrence of ripples with theta-frequency oscillations in the hippocampus of foraging rats

Background and motivationBrain rhythms have been postulated to play central roles in animal cognition. A prominently reported dichotomy of hippocampal rhythms, driven primarily by historic single-strata recordings, assigns theta-frequency oscillations (4-12 Hz) and ripples (120-250 Hz) to be exclusively associated with preparatory and consummatory behaviors, respectively. However, due to the differential power expression of these two signals across hippocampal strata, reports of such exclusivity require validation through simultaneous multi-strata recordings and cross-strata analysis of these oscillatory patterns. MethodologyWe assessed co-occurrence of theta-frequency oscillations with ripples in multi-channel recordings of extracellular potentials across hippocampal strata from foraging rats. We detected all ripple events from an identified stratum pyramidale (SP) channel based on rigorous thresholds relating to the spectro-temporal and spatial characteristics of ripples. We then defined theta epochs based on theta oscillations detected from each of the different channels spanning the SP to the stratum lacunosum-moleculare (SLM) through the stratum radiatum (SR). We calculated the proportion of ripples embedded within theta epochs. ResultsWe found [~]20% (across rats) of ripple events (in SP) to co-occur with theta epochs identified from SR/SLM channels, defined here as theta ripples. All characteristics of theta ripples were comparable with ripples that occurred in the absence of theta oscillations. Furthermore, the power of theta oscillations in the immediate vicinity of theta ripples was similar to theta power across identified theta epochs, together validating the identification process of theta ripples. Strikingly, when theta epochs were instead identified from the SP channel, such co-occurrences were significantly lower in number. The reduction in the number of theta ripples was consequent to progressive reduction in theta power along the SLM-SR-SP axis. We assessed the behavioral state of rats during ripple events and found most theta ripples to occur during immobile periods. We confirmed that across sessions and rats, the theta power observed during exploratory theta epochs was comparable with theta power during immobile theta epochs. In addition, the progressive reduction in theta power along the SLM-SR-SP axis was common to both exploratory and immobile periods. Finally, we found a strong theta-phase preference of theta ripples within the third quadrant [3{pi}/2-2{pi}] of the associated theta oscillation. ImplicationsOur analyses provide direct quantitative evidence for the occurrence of ripple events nested within theta oscillations in the rodent hippocampus. These analyses emphasize that the prevalent dichotomy about the manifestation of theta-frequency oscillations and ripples needs to be reevaluated, after explicitly accounting for the differential stratum-dependent expression of these two oscillatory patterns. The prevalence of theta ripples expands the potential roles of ripple-frequency oscillations to span the continuum of encoding, retrieval, and consolidation, achieved through interactions with theta oscillations.

neuroscience↗

bioRxiv2022

Identification of potential natural compound inhibitors and drug like molecules against human METTL3 by docking and molecular dynamics simulation

Nucleotide level chemical modification in transcriptome is critical in regulating different cellular processes, including cancer. The most investigated epitranscriptomic modification is methylation at the N6-position of adenosine (m6A). This dynamic modification process is carried out by: writer, reader and eraser proteins. Writers are methyltransferases, METTL3 is the major writer that works in association with METTL14, an accessory protein. Extensive study revealed that cancer progression for acute myeloid leukaemia, gastric cancer, colorectal cancer, hepatocellular carcinoma, and lung cancer is directly contributed by irregular expression of METTL3. Targeting METTL3, has opened a new window in the development of new inhibitors/drugs. In this study, 80 commercially available compounds were found from an unbiased screening by molecular docking, showing better score when compared with the existing substrate/substrate-analogue and the inhibitor bound crystal structures in terms of docking score and binding energy calculation. Among this pool of compounds, the best seven small molecules, AMF, RAD, JNJ, MEH, ECP, MHN, SGI, have been selected and further validated by different computational tools like binding energy calculation, molecular dynamics simulation etc. The novel hits found in this study can function as lead compounds which can be developed into inhibitors as well as drugs, specific against METTL3.

bioinformatics↗

bioRxiv2021

Focal Laser Stimulation of Fly Nociceptors Activates Distinct Axonal and Dendritic Ca2+ Signals

Drosophila Class IV neurons are polymodal nociceptors that detect noxious mechanical, thermal, optical and chemical stimuli. Escape behaviors in response to attacks by parasitoid wasps are dependent on Class IV cells, whose highly branched dendritic arbors form a fine meshwork that is thought to enable detection of the wasps needle-like ovipositor barb. To understand how mechanical stimuli trigger cellular responses, we used a focused 405-nm laser to create highly local lesions to probe the precise position needed in evoke responses. By imaging calcium signals in dendrites, axons, and soma in response to stimuli of varying positions, intensities and spatial profiles, we discovered that there are two distinct nociceptive pathways. Direct stimulation to dendrites (the contact pathway) produces calcium responses in axons, dendrites and the cell body whereas stimulation adjacent to the dendrite (the non-contact pathway) produces calcium responses in the axons only. We interpret the non-contact pathway as damage to adjacent cells releasing diffusible molecules that act on the dendrites. Axonal responses have higher sensitivities and shorter latencies. In contrast, dendritic responses have lower sensitivities and longer latencies. Stimulation of finer, distal dendrites leads to smaller responses than stimulation of coarser, proximal dendrites, as expected if the contact response depends on the geometric overlap of the laser profile and the dendrite diameter. Because the axon signals to the CNS to trigger escape behaviors, we propose that the density of the dendritic meshwork is high not only to enable direct contact with the ovipositor, but also to enable neuronal activation via diffusing signals from damaged surrounding cells. Dendritic contact evokes responses throughout the dendritic arbor, even to regions distant and distal from the stimulus. These dendrite-wide calcium signals may facilitate hyperalgesia or cellular morphological changes following dendritic damage. Statement of SignificanceAnimals encounter a wide range of noxious stimuli in the natural world. Nociceptive neurons are specialized cells that sense harmful stimuli and trigger avoidance responses. Class IV cells, located under the cuticle in Drosophila larvae, are polymodal nociceptors that respond to noxious mechanical, thermal, optical, and chemical stimuli. To investigate the spatial requirements of mechanoreception in Class IV neurons, we measured calcium signals evoked by a focused laser beam that creates highly localized tissue damage. We discovered that different cellular compartments - axons and dendrites - responded differentially depending on whether the stimulus makes direct contact with the neuron or not. This provides evidence that mechanical nociception in Class IV cells occurs via two distinct pathways.

neuroscience↗

bioRxiv2019

Robust emergence of sharply tuned place cell responses in hippocampal neurons with structural and biophysical heterogeneities

Hippocampal pyramidal neurons sustain propagation of fast electrical signals and are electrotonically non-compact structures exhibiting cell-to-cell variability in their complex dendritic arborization. In this study, we demonstrate that sharp place-field tuning and several somato-dendritic functional maps concomitantly emerge despite the presence of geometrical heterogeneities in these neurons. We establish this employing an unbiased stochastic search strategy involving thousands of models that spanned several morphologies and distinct profiles of dispersed synaptic localization and channel expression. Mechanistically, employing virtual knockout models, we explored the impact of bidirectional modulation in dendritic spike prevalence on place-field tuning sharpness. Consistent with prior literature, we found that across all morphologies, virtual knockout of either dendritic fast sodium channels or N-methyl-D-aspartate receptors led to a reduction in dendritic spike prevalence, whereas A-type potassium channel knockouts resulted in a nonspecific increase in dendritic spike prevalence. However, place-field tuning sharpness was critically impaired in all three sets of virtual knockout models, demonstrating that sharpness in feature tuning is maintained by an intricate balance between mechanisms that promote and those that prevent dendritic spike initiation. From the functional standpoint of the emergence of sharp feature tuning and intrinsic functional maps, within this framework, geometric variability was compensated by a combination of synaptic democracy, the ability of randomly dispersed synapses to yield sharp tuning through dendritic spike initiation, and ion-channel degeneracy. Our results suggest electrotonically non-compact neurons to be endowed with several degrees of freedom, encompassing channel expression, synaptic localization and morphological micro-structure, in achieving sharp feature encoding and excitability homeostasis.

neuroscience↗

bioRxiv2017

Spatially dispersed synapses yield sharply-tuned place cell responses through dendritic spike initiation

The literature offers evidence for a critical role of spatially-clustered iso-feature synapses in eliciting dendritic spikes essential for sharp feature selectivity, with apparently contradictory evidence demonstrating spatial dispersion of iso-feature synapses. Here, we reconcile this apparent contradiction by demonstrating that the generation of dendritic spikes, the emergence of an excitatory ramp in somatic voltage responses and sharp tuning of place-cell responses are all attainable even when iso-feature synapses are randomly dispersed across the dendritic arbor. We found this tuning sharpness to be critically reliant on dendritic sodium and transient potassium channels and on N-methyl-D-aspartate receptors. Importantly, we demonstrate that synaptic potentiation targeted to afferents from one specific place field is sufficient to effectuate place-field selectivity even when intrinsically disparate neurons received randomly dispersed afferents from multiple place-field locations. These conclusions proffer dispersed localization of isofeature synapses as a strong candidate for achieving sharp feature selectivity in neurons across sensory-perceptual systems.\n\nO_LSTHighlightsC_LSTO_LISystematic analysis of four synaptic localization profiles for sharp spatial tuning\nC_LIO_LIDendritic spikes are generated even with randomly dispersed iso-feature synapses\nC_LIO_LISharp feature tuning could be achieved even in the absence of synaptic clusters\nC_LIO_LITargeted, yet dispersed, synaptic plasticity sufficient for place-cell emergence\nC_LI

neuroscience↗