Biology subjects

Rama, R.

Publications and source records attributed to Rama, R..

4 recordsLinked to original sources

bioRxiv2025

Serotonin Engages Divergent 5-HT Receptor Pathways for Cell Type-Resolved Modulation of Prefrontal Layer 5 Microcircuits

Background and PurposeSerotonin (5-HT) is a key neuromodulator in the prefrontal cortex (PFC), yet its cell type-specific effects across excitatory and inhibitory microcircuits remain incompletely understood. We aimed to determine how 5-HT shapes intrinsic excitability and synaptic transmission in defined neuronal populations of the medial PFC (mPFC). Experimental ApproachWe performed whole-cell recordings from morphologically and electrophysiologically characterised layer 5 (L5) neurons in rat mPFC. Pyramidal neurons were classified into adaptive-spiking high input resistance (ASH), adaptive-spiking low input resistance (ASL), and regular-spiking (RS) types; interneurons were categorised as non-fast-spiking (nFS), regular-fast-spiking (rFS), and stuttering-fast-spiking (sFS) interneurons. These cell types exhibited distinct membrane properties, firing patterns, and axonal projections. We assessed serotonergic modulation using bath-applied 5-HT and subtype-specific receptor mechanisms. Key Results5-HT produced divergent postsynaptic responses across pyramidal neuron subtypes: ASH and RS neurons depolarised via 5-HT2A receptor (5-HT2AR) activation, whereas ASL neurons exhibited 5-HT1AR-mediated hyperpolarisation. Among interneurons, rFS and sFS cells depolarised through ionotropic 5-HT3ARs, while nFS interneurons were largely unaffected. At the synaptic level, 5-HT suppressed excitatory synaptic transmission between pyramidal neurons via presynaptic 5-HT1BRs, and conversely enhanced GABAergic transmission from FS interneurons via presynaptic 5-HT3ARs. Conclusions & ImplicationsSerotonin exerts bidirectional, cell type-specific serotonergic modulation of local microcircuits that acts to suppress excitation while facilitating inhibition. This balanced and targeted regulation, arising from distinct distributions of somatodendritic and presynaptic 5-HT receptors, provides a mechanistic basis for serotonergic influence on attention, cognitive flexibility, and emotional regulation.

neuroscience↗

bioRxiv2024

Copy number variations of Plasmodium vivax DBP1, EBP/DBP2, and RBP2b in Duffy-positive and Duffy-negative Ethiopians

Recent evidence challenges the belief that Duffy-negative individuals are resistant to Plasmodium vivax due to lacking Duffy Antigen Receptor for Chemokines (DARC). Erythrocyte Binding Protein (EBP/DBP2) has shown moderate binding to Duffy-negative erythrocytes in vitro. Reticulocyte Binding Protein 2b (RBP2b) interactions with Transferrin Receptor 1 (TfR1) suggest involvement in Duffy-negative infections. Gene copy number variations in PvDBP1, PvEBP/DBP2, and PvRBP2b were investigated in Duffy-positive and Duffy-negative P. vivax-infected individuals from Ethiopia. Among Duffy-positive samples, 34% displayed PvDBP1 duplications (Cambodian-type). In Duffy-negative infections, 30% showed duplications, mostly Cambodian-type. For PvEBP/DBP2 and PvRBP2b, Duffy-positive samples exhibited higher duplication rates (1-8 copies for PvEBP/DBP2, 1-5 copies for PvRBP2b 46% and 43% respectively) compared to Duffy-negatives (20.8% and 26% respectively). The range of copy number variations was lower in Duffy-negative infections. Demographic and clinical factors associated with gene multiplications in both Duffy types were explored, enhancing understanding of P. vivax evolution in Duffy-negative Africans.

microbiology↗

bioRxiv2019

Multimodal Study of the Effects of Varying Task Load Utilizing EEG, GSR and Eye-Tracking

ObjectiveThe effect of task load on performance is investigated by simultaneously collecting multi-modal physiological data and participant response data. Periodic response to a questionnaire is also obtained. The goal is to determine combinations of modalities that best serve as predictors of task performance.\n\nApproachA group of participants performed a computer-based visual search task mimicking postal code sorting. A five-digit number had to be assigned to one of six different non-overlapping numeric ranges. Trials were presented in blocks of progressively increasing task difficulty. The participants responses were collected simultaneously with 32 channels of electroencephalography (EEG) data, eye-tracking data, and Galvanic Skin Response (GSR) data. The NASA Task-Load-Index self-reporting instrument was administered at discrete time points in the experiment.\n\nMain resultsLow beta frequency EEG waves (12.5-18 Hz) were more prominent as cognitive task load increased, with most activity in frontal and parietal regions. These were accompanied by more frequent eye blinks and increased pupillary dilation. Blink duration correlated strongly with task performance. Phasic components of the GSR signal were related to cognitive workload, whereas tonic components indicated a more general state of arousal. Subjective data (NASA TLX) as reported by the participants showed an increase in frustration and mental workload. Based on one-way ANOVA, EEG and GSR provided the most reliable correlation to perceived workload level and were the most informative measures (taken together) for performance prediction.\n\nSignificanceNumerous modalities come into play during task-related activity. Many of these modalities can provide information on task performance when appropriately grouped. This study suggests that while EEG is a good predictor of task performance, additional modalities such as GSR increase the likelihood of more accurate predictions. Further, in controlled laboratory conditions, the most informative or minimum number of modalities can be isolated for monitoring in real work environments.

neuroscience↗

bioRxiv2019

TRAF6 controls excitatory spinogenesis and excitation-inhibition balance thought binding neuroplastin

Synaptogenic mechanisms and their relevance to achieve a correct synapse density and activity in mature neurons are poorly understood. Here, we show that the tumor necrosis factor receptor-associated factor 6 (TRAF6) controls early spinogenesis by binding the cell adhesion molecule neuroplastin which is has been related to synapse formation in vivo. TRAF6-neuroplastin co-precipitations from brain samples and co-transfected HEK cells is explained by direct interaction of the proteins based on three-dimensional modelling and biochemical identification of intracellular amino acids of neuroplastin binding the TRAF-C domain of TRAF6 with micromolar affinity. TRAF6 was not only required for normal spinogenesis but also was strictly necessary to restore failed spinogenesis in neuroplastin-deficient neurons. Independently from neuroplastins extracellular adhesive properties or interaction with another known partner i.e. the plasma membrane Ca2+ ATPases, TRAF6 mediated formation of new postsynapses by neuroplastin overexpression in rat hippocampal neurons. Furthermore, TRAF6-controlled spinogenesis was required for the establishment of a correct synapse density as well as proper synaptic activity and intrinsic neuronal activity as demonstrated with intracellular and extracellular electrophysiological recordings. These findings provide a novel mechanism for early synapse formation that shapes connectivity and functioning of hippocampal neurons.

cell biology↗