Mechanisms of ocular dominance plasticity in the juvenile and adult mouse visual cortex

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011.Cataloged from PDF version of thesis. Vita.Includes bibliographical references (p. 171-185).Ocular dominance (OD) plasticity is a classic example of bidirectional experience-dependent plasticity in the primary visual cortex. This form of plasticity is most robust during early postnatal development (termed the "critical period"), when monocular deprivation (MD) leads to a rapid weakening of responses evoked through the deprived eye followed by a delayed strengthening of non-deprived eye inputs. It has been proposed that these bidirectional changes occur as a three-stage process: first, degradation of patterned visual input weakens deprived-eye responses via homosynaptic long-term depression (LTD); this is accompanied by a shift in the plasticity modification threshold (0m) that determines the direction of synaptic plasticity, such that synaptic strengthening is favored over synaptic weakening; finally, weak open-eye responses are strengthened via the mechanisms of homosynaptic long-term potentiation (LTP). Despite the growing evidence supporting this model of experience-dependent synaptic modification, the exact molecular and synaptic mechanisms that are responsible for these processes remain controversial. In my thesis work, I address three questions. First, I attempt to parse the relative contribution of excitatory and inhibitory processes to expression of the OD shift in order to understand how deprived-eye depression is expressed in the cortex. To address this, I first induce a shift in OD with 3 days of MD and then use several pharmacological methods to shut off cortical inhibitory synaptic transmission. I demonstrate that rapid deprived-eye depression is strongly expressed at excitatory thalamocortical synapses without any influences of polysynaptic intracortical inhibition. In the second part of my work, I try to resolve the nature/identity of the molecular mechanism that underlies the regulation of [theta]m. Using a transgenic mouse model, I find that a reduction in the NR2A/B subunit ratio of the N-methyl-d-aspartate (NMDA) receptor during MD alters the qualities of OD plasticity by impairing weakening of deprived-eye inputs and enhancing strengthening of open-eye inputs. These findings suggest that NMDAR subunit composition may specify the value and the rate of adjustment of synaptic 0m, which in turn determines the bidirectional cortical response to MD. The final portion of my thesis addresses the factors that limit OD plasticity beyond the critical period. I test the hypothesis that the developmental increase in intracortical GABAergic inhibitory synaptic transmission is a fundamental restricting factor for adult cortical plasticity and demonstrate that parvalbumin-expressing fast-spiking basket cells are specifically implicated in the absence of juvenile-like deprived-eye depression in adult mice.by Lena A. Khibnik.Ph.D

A Direct Projection from Mouse Primary Visual Cortex to Dorsomedial Striatum

The mammalian striatum receives inputs from many cortical areas, but the existence of a direct axonal projection from the primary visual cortex (V1) is controversial. In this study we use anterograde and retrograde tracing techniques to demonstrate that V1 directly innervates a topographically defined longitudinal strip of dorsomedial striatum in mice. We find that this projection forms functional excitatory synapses with direct and indirect pathway striatal projection neurons (SPNs) and engages feed-forward inhibition onto these cells. Importantly, stimulation of V1 afferents is sufficient to evoke phasic firing in SPNs. These findings therefore identify a striatal region that is functionally innervated by V1 and suggest that early visual processing may play an important role in striatal-based behaviors

Geometrical Properties of Coupled Oscillators at Synchronization

We study the synchronization of $N$ nearest neighbors coupled oscillators in a ring. We derive an analytic form for the phase difference among neighboring oscillators which shows the dependency on the periodic boundary conditions. At synchronization, we find two distinct quantities which characterize four of the oscillators, two pairs of nearest neighbors, which are at the border of the clusters before total synchronization occurs. These oscillators are responsible for the saddle node bifurcation, of which only two of them have a phase-lock of phase difference equals $\pm$$\pi$/2. Using these properties we build a technique based on geometric properties and numerical observations to arrive to an exact analytic expression for the coupling strength at full synchronization and determine the two oscillators that have a phase-lock condition of $\pm$$\pi$/2.Comment: accepted for publication in "Communications in Nonlinear Science and Numerical Simulations

System Identification for Limit Cycling Systems: A Case Study for Combustion Instabilities

This paper presents a case study in system identification for limit cycling systems. The focus of the paper is on (a) the use of model structure derived from physcal considerations and (b) the use of algorithms for the identification of component subsystems of this model structure. The physical process used in this case study is that of a reduced order model for combustion instabilities for lean premixed systems. The identification techniques applied in this paper are the use of linear system identification tools (prediction error methods), time delay estimation (based on Kalman filter harmonic estimation methods) and qualitative validation of model properties using harmonic balance and describing function methods. The novelty of the paper, apart from its practical application, is that closed loop limit cycle data is used together with a priori process structural knowledge to identify both linear dynamic forward and nonlinear feedback paths. Future work will address the refinement of the process presented in this paper, the use of alternative algorithms and also the use of control approachs for the validated model structure obtained from this paper

Modeling the dynamics of glacial cycles

This article is concerned with the dynamics of glacial cycles observed in the geological record of the Pleistocene Epoch. It focuses on a conceptual model proposed by Maasch and Saltzman [J. Geophys. Res.,95, D2 (1990), pp. 1955-1963], which is based on physical arguments and emphasizes the role of atmospheric CO2 in the generation and persistence of periodic orbits (limit cycles). The model consists of three ordinary differential equations with four parameters for the anomalies of the total global ice mass, the atmospheric CO2 concentration, and the volume of the North Atlantic Deep Water (NADW). In this article, it is shown that a simplified two-dimensional symmetric version displays many of the essential features of the full model, including equilibrium states, limit cycles, their basic bifurcations, and a Bogdanov-Takens point that serves as an organizing center for the local and global dynamics. Also, symmetry breaking splits the Bogdanov-Takens point into two, with different local dynamics in their neighborhoods

DBSolve Optimum: a software package for kinetic modeling which allows dynamic visualization of simulation results

<p>Abstract</p> <p>Background</p> <p>Systems biology research and applications require creation, validation, extensive usage of mathematical models and visualization of simulation results by end-users. Our goal is to develop novel method for visualization of simulation results and implement it in simulation software package equipped with the sophisticated mathematical and computational techniques for model development, verification and parameter fitting.</p> <p>Results</p> <p>We present mathematical simulation workbench DBSolve Optimum which is significantly improved and extended successor of well known simulation software DBSolve5. Concept of "dynamic visualization" of simulation results has been developed and implemented in DBSolve Optimum. In framework of the concept graphical objects representing metabolite concentrations and reactions change their volume and shape in accordance to simulation results. This technique is applied to visualize both kinetic response of the model and dependence of its steady state on parameter. The use of the dynamic visualization is illustrated with kinetic model of the Krebs cycle.</p> <p>Conclusion</p> <p>DBSolve Optimum is a user friendly simulation software package that enables to simplify the construction, verification, analysis and visualization of kinetic models. Dynamic visualization tool implemented in the software allows user to animate simulation results and, thereby, present them in more comprehensible mode. DBSolve Optimum and built-in dynamic visualization module is free for both academic and commercial use. It can be downloaded directly from <url>http://www.insysbio.ru</url>.</p

Daphnia revisited: Local stability and bifurcation theory for physiologically structured population models explained by way of an example

We consider the interaction between a general size-structured consumer population and an unstructured resource. We show that stability properties and bifurcation phenomena can be understood in terms of solutions of a system of two delay equations (a renewal equation for the consumer population birth rate coupled to a delay differetial equation for the resource concentration). As many results for such systems are available, we can draw rigorous conclusions concerning dynamical behaviour from an analysis of a characteristic equation. We derive the characteristic equation for a fairly general class of population models, including those based on the Kooijman-Metz Daphnia model and a model introduced by Gurney-Nisbet and Jones et al., and next obtain various ecological insights by analytical or numerical studies of special cases

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit