Shyam Diwakar

Axonal Na+ Channels Ensure Fast Spike Activation and Back-Propagation in Cerebellar Granule Cells

In most neurons, Na+ channels in the axon are complemented by others localized in the soma and dendrites to ensure spike back-propagation. However, cerebellar granule cells are neurons with simplified architecture in which the dendrites are short and unbranched and a single thin ascending axon travels toward the molecular layer before bifurcating into parallel fibers. Here we show that in cerebellar granule cells, Na+ channels are enriched in the axon, especially in the hillock, but almost absent from soma and dendrites. The impact of this channel distribution on neuronal electroresponsiveness was investigated by multi-compartmental modeling. Numerical simulations indicated that granule cells have a compact electrotonic structure allowing excitatory postsynaptic potentials to diffuse with little attenuation from dendrites to axon. The spike arose almost simultaneously along the whole axonal ascending branch and invaded the hillock the activation of which promoted spike back-propagation with marginal delay (<200 micros) and attenuation (<20 mV) into the somato-dendritic compartment. These properties allow granule cells to perform sub-millisecond coincidence detection of pre- and postsynaptic activity and to rapidly activate Purkinje cells contacted by the axonal ascending branch.

Altered Neuron Excitability and Synaptic Plasticity in the Cerebellar Granular Layer of Juvenile Prion Protein Knock-Out Mice with Impaired Motor Control

Although the role of abnormal prion protein (PrP) conformation in generating infectious brain diseases (transmissible spongiform encephalopathy) has been recognized, the function of PrP in the normal brain remains mostly unknown. In this investigation, we considered the effect of PrP gene knock-out (PrP0/0) on cerebellar neural circuits and in particular on granule cells, which show intense PrP expression during development and selective affinity for PrP. At the third postnatal week, when PrP expression would normally attain mature levels, PrP0/0 mice showed low performance in the accelerating rotarod and runway tests and the functioning of 40% of granule cells was abnormal. Spikes were slow, nonovershooting, and nonrepetitive in relation with a reduction in transient inward and outward membrane currents, and also the EPSPs and EPSCs had slow kinetics. Overall, these alterations closely resembled an immature phenotype. Moreover, in slow-spiking PrP0/0 granule cells, theta-burst stimulation was unable to induce any long-term potentiation. This profound impairment in synaptic excitation and plasticity was associated with a protracted proliferation of granule cells and disappeared at P40–P50 along with the recovery of normal motor behavior (Büeler et al., 1992). These results suggest that PrP plays an important role in granule cell development eventually regulating cerebellar network formation and motor control.

Local Field Potential Modeling Predicts Dense Activation in Cerebellar Granule Cells Clusters under LTP and LTD Control

Local field-potentials (LFPs) are generated by neuronal ensembles and contain information about the activity of single neurons. Here, the LFPs of the cerebellar granular layer and their changes during long-term synaptic plasticity (LTP and LTD) were recorded in response to punctate facial stimulation in the rat in vivo. The LFP comprised a trigeminal (T) and a cortical (C) wave. T and C, which derived from independent granule cell clusters, co-varied during LTP and LTD. To extract information about the underlying cellular activities, the LFP was reconstructed using a repetitive convolution (ReConv) of the extracellular potential generated by a detailed multicompartmental model of the granule cell. The mossy fiber input patterns were determined using a Blind Source Separation (BSS) algorithm. The major component of the LFP was generated by the granule cell spike Na+ current, which caused a powerful sink in the axon initial segment with the source located in the soma and dendrites. Reproducing the LFP changes observed during LTP and LTD required modifications in both release probability and intrinsic excitability at the mossy fiber-granule cells relay. Synaptic plasticity and Golgi cell feed-forward inhibition proved critical for controlling the percentage of active granule cells, which was 11% in standard conditions but ranged from 3% during LTD to 21% during LTP and raised over 50% when inhibition was reduced. The emerging picture is that of independent (but neighboring) trigeminal and cortical channels, in which synaptic plasticity and feed-forward inhibition effectively regulate the number of discharging granule cells and emitted spikes generating “dense” activity clusters in the cerebellar granular layer.

The VALUE @ Amrita Virtual Labs Project: Using Web Technology to Provide Virtual Laboratory Access to Students

In response to the Indian Ministry of Human Resource Development (MHRD) National Mission on Education through Information and Communication Technology (NME-ICT) Initiative, the Virtual and Accessible Laboratories Universalizing Education (VALUE @ Amrita) Virtual Labs Project was initiated to provide laboratory-learning experiences to college and university students across India who may not have access to adequate laboratory facilities or equipment. These virtual laboratories require only a broadband Internet connection and standard web browser. Amrita Vishwa Vidyapeetham University (Amrita University) is part of a consortium of twelve institutions building over two hundred virtual labs covering nine key disciplines in science and engineering. This National Mission project hopes to reach out to Indias millions of engineering and science students at both undergraduate and postgraduate levels. The Virtual Labs Project is providing virtual laboratory experiments that directly support the All India Council for Technical Education (AICTE) and the University Grants Commission (UGC) model curricula for engineering and sciences undergraduate and postgraduate programs.

Modeling spike-train processing in the cerebellum granular layer and changes in plasticity reveal single neuron effects in neural ensembles

The cerebellum input stage has been known to perform combinatorial operations on input signals. In this paper, two types of mathematical models were used to reproduce the role of feed-forward inhibition and computation in the granular layer microcircuitry to investigate spike train processing. A simple spiking model and a biophysically-detailed model of the network were used to study signal recoding in the granular layer and to test observations like center-surround organization and time-window hypothesis in addition to effects of induced plasticity. Simulations suggest that simple neuron models may be used to abstract timing phenomenon in large networks, however detailed models were needed to reconstruct population coding via evoked local field potentials (LFP) and for simulating changes in synaptic plasticity. Our results also indicated that spatio-temporal code of the granular network is mainly controlled by the feed-forward inhibition from the Golgi cell synapses. Spike amplitude and total number of spikes were modulated by LTP and LTD. Reconstructing granular layer evoked-LFP suggests that granular layer propagates the nonlinearities of individual neurons. Simulations indicate that granular layer network operates a robust population code for a wide range of intervals, controlled by the Golgi cell inhibition and is regulated by the post-synaptic excitability.

Enhanced facilitation of biotechnology education in developing nations via virtual labs: analysis, implementation and case-studies

Methods for educating students in biotechnology require intensive training in laboratory procedures. Laboratory procedures cost Universities in terms of equipment and experienced guidance which often come short in many developing countries. Universities need revitalizing approach and well-adapted curriculum especially in terms of laboratory practice. For enhanced education at the level of University-level laboratory courses such as those in biology or biotechnology, one of the key elements is the need to allow the student to familiarize laboratory techniques in par with regular theory. The Sakshat Amrita virtual biotechnology lab project focusing on virtualizing wet-lab techniques and integrating the learning experience has added a new dimension to the regular teaching courses at the University. Establishing virtual labs requires both domain knowledge and virtualizing skills via programming, animation and device-based feedback. This paper reports a cost-effective process used in virtualizing real biotechnology labs for education at Universities. The major challenge in setting up an effective knowledge dissemination for laboratory courses was not only the scientific approach of biotechnology, but included the virtualization aspects such as usage/design scalability, deliverability efficiency, network connectivity issues, security and speed of adaptability to incorporate and update changes into existing experiments. This paper also discusses an issue-specific case-study of a functional virtual lab in biotechnology and its many issues and challenges.

Remote triggered photovoltaic solar cell lab: Effective implementation strategies for Virtual Labs

Remote triggered laboratories are an excellent way to provide access to costly labs and equipment for students in areas without such facilities. A novel remote triggered photovoltaic solar cell experiment is presented here. This experiment enables the student to learn in a hands-on, practical way about the fundamental characteristics of photovoltaic solar cells. The experiment has a web interface in which the student can turn a number of light bulbs on and off, adjust the load voltage of the solar cell, and view the experiment in real-time via a web-cam. In addition, the characteristics of the solar cells under these various conditions are measured and displayed on the web interface in a spreadsheet and are plotted in a novel and learning-effective manner. This experiment has been hosted on our Virtual Labs website for over a year, with a large number of students using the site. This paper presents implementation strategies and methods used which have proven effective for Virtual Labs, along with a technical description of the experiment and the system used to create and host the experiment.

Biotechnology Virtual Labs - Integrating Wet-lab Techniques and Theoretical Learning for Enhanced Learning at Universities

For enhanced education at the level of University courses such as those in biology or biotechnology, one of the key elements is the need of time and expertise to allow the student to familiarize laboratory techniques in par with regular theory. The Sakshat Amrita virtual biotechnology lab project focusing on virtualizing wet-lab techniques and integrating the learning experience has added a new dimension to the regular teaching courses at the University. Establishing virtual labs requires both domain knowledge and virtualizing skills via programming, animation and device-based feedback. Challenges in the biotechnology sector in setting up a laboratory that integrates both the feel and phenomenon includes the medley of multiple techniques. This paper reports one such cost-effective process used in virtualizing a real biotechnology lab at the University-level. The major challenge in setting up an effective knowledge dissemination for laboratory courses was not only the scientific approach of biotechnology, but included the virtualization aspects such as usage/design scalability, deliverability efficiency, network connectivity issues, security and speed of adaptability to incorporate and update changes into existing experiments. This paper also discusses an issue-specific case-study of a functional virtual lab in biotechnology and its many issues and challenges.

Biotechnology Virtual Labs: Facilitating Laboratory Access Anytime-Anywhere for Classroom Education

Biotechnology is becoming more popular and well identified as a mainline industry. Students have shown greater interest in learning the techniques. As a discipline, biotechnology has led to new advancements in many areas. Criminal investigation has changed dramatically thanks to DNA fingerprinting. Significant advances in forensic medicine, anthropology and wildlife management have been noticed in the last few years. Biotechnology has brought out hundreds of medical diagnostic tests that keep the blood safe from infectious diseases such as HIV and also aid detection of other conditions early enough to be successfully treated. Medical kits for diabetes, blood cholesterol and home pregnancy tests are also biotechnology diagnostic products. Industrial biotech applications have led to cleaner processes that produce less waste and use less energy and water in such industrial sectors as chemicals, pulp and paper, textiles, food, energy, and metals and minerals. Laundry detergents produced in many countries contain biotechnology-based enzymes making them nature friendly and safer. Agricultural biotechnology benefits farmers, consumers and the environment by increasing yields and farm income, decreasing pesticide applications and improving soil and water quality, and providing healthful foods for consumers. Biotechnology has created more than 200 new therapies and vaccines, including products to treat cancer, diabetes, HIV/ AIDS and autoimmune disorders.

Modeling cerebellar granular layer excitability and combinatorial computation with spikes

The cerebellum input stage has been known to perform combinatorial operations [1] [3] on input signals. In this paper, we developed a model to study information transmission and signal recoding in the cerebellar granular layer and to test observations like center-surround organization and time-window hypothesis [1] [2]. We also developed simple neuron models for abstracting timing phenomena in large networks. Detailed biophysical models were used to study synaptic plasticity and its effect in generation and modulation of spikes in the granular layer network. Our results indicated that spatio-temporal information transfer through the granular network is controlled by synaptic inhibition [1]. Spike amplitude and number of spikes were modulated by L TP and LTD. Both in vitro and in vivo simulations indicated that inhibitory input via Golgi cells acts as a modulator and regulates the post synaptic excitability.