A Population Density Model of the Driven LGN/PGN

The interaction of two populations of integrate-and-fire-or-burst neurons representing thalamocortical cells from the dorsal lateral geniculate nucleus (dLGN) and thalamic reticular cells from the perigeniculate nucleus (PGN) is studied using a population density approach. A two-dimensional probability density function that evolves according to a time-dependent advection-reaction equation gives the distribution of cells in each population over the membrane potential and de-inactivation level of a low-threshold calcium current. In the absence of retinal drive, the population density network model exhibits rhythmic bursting. In the presence of constant retinal input, the aroused LGN/PGN population density model displays a wide range of responses depending on cellular parameters and network connectivity.https://scholarworks.wm.edu/asbookchapters/1130/thumbnail.jp

Towards building a more complex view of the lateral geniculate nucleus: Recent advances in understanding its role

The lateral geniculate nucleus (LGN) has often been treated in the past as a linear filter that adds little to retinal processing of visual inputs. Here we review anatomical, neurophysiological, brain imaging, and modeling studies that have in recent years built up a much more complex view of LGN . These include effects related to nonlinear dendritic processing, cortical feedback, synchrony and oscillations across LGN populations, as well as involvement of LGN in higher level cognitive processing. Although recent studies have provided valuable insights into early visual processing including the role of LGN, a unified model of LGN responses to real-world objects has not yet been developed. In the light of recent data, we suggest that the role of LGN deserves more careful consideration in developing models of high-level visual processing

Silences, Spikes and Bursts: Three-Part Knot of the Neural Code

When a neuron breaks silence, it can emit action potentials in a number of patterns. Some responses are so sudden and intense that electrophysiologists felt the need to single them out, labeling action potentials emitted at a particularly high frequency with a metonym -- bursts. Is there more to bursts than a figure of speech? After all, sudden bouts of high-frequency firing are expected to occur whenever inputs surge. The burst coding hypothesis advances that the neural code has three syllables: silences, spikes and bursts. We review evidence supporting this ternary code in terms of devoted mechanisms for burst generation, synaptic transmission and synaptic plasticity. We also review the learning and attention theories for which such a triad is beneficial.Comment: 15 pages, 4 figure

The thalamocortical symphony:How thalamus and cortex play together in schizophrenia and plasticity

The work presented in this thesis aimed at investigating the function and mechanism of corticothalamic-thalamocortical network in schizophrenia and experience-dependent plasticity, further discussed their possible connection.In Chapter 2, we examined the effects of low-dose ketamine on the corticothalamic circuit (CTC) system. Our findings reveal that ketamine induces abnormal spindle activity and gamma oscillations in the CTC system. Notably, ketamine also leads to a transition in thalamic neurons from burst-firing to tonic action potential mode, which may underlie deficits in spindle oscillations. Chapter 3 addresses sensory perception deficits in schizophrenia, emphasizing disruptions in beta and gamma frequency oscillations due to signal-to-noise ratio imbalances. Chapter 4 explores experience-dependent plasticity, highlighting the role of thalamic synaptic inhibition in ocular dominance plasticity and the influence of cortical feedback. Chapter 5 investigates the involvement of endocannabinoids, particularly CB1 receptors, in inhibitory synaptic maturation and ocular dominance plasticity within the primary visual cortex.The general discussion raises the possibility of a link between neural plasticity and schizophrenia, particularly during the transformative phase of adolescence when the brain undergoes significant changes. An abnormal balance between inhibition and excitation, influenced by GABAergic maturation deficits, connectivity disruptions, and altered perceptual information transfer, may contribute to the development of schizophrenia.This thesis offers valuable insights into the intricate mechanisms underlying schizophrenia, with a particular focus on the CTC circuit, NMDA receptors, and endocannabinoids in the context of neuronal plasticity and cognitive function

The thalamocortical symphony:How thalamus and cortex play together in schizophrenia and plasticity

The work presented in this thesis aimed at investigating the function and mechanism of corticothalamic-thalamocortical network in schizophrenia and experience-dependent plasticity, further discussed their possible connection.In Chapter 2, we examined the effects of low-dose ketamine on the corticothalamic circuit (CTC) system. Our findings reveal that ketamine induces abnormal spindle activity and gamma oscillations in the CTC system. Notably, ketamine also leads to a transition in thalamic neurons from burst-firing to tonic action potential mode, which may underlie deficits in spindle oscillations. Chapter 3 addresses sensory perception deficits in schizophrenia, emphasizing disruptions in beta and gamma frequency oscillations due to signal-to-noise ratio imbalances. Chapter 4 explores experience-dependent plasticity, highlighting the role of thalamic synaptic inhibition in ocular dominance plasticity and the influence of cortical feedback. Chapter 5 investigates the involvement of endocannabinoids, particularly CB1 receptors, in inhibitory synaptic maturation and ocular dominance plasticity within the primary visual cortex.The general discussion raises the possibility of a link between neural plasticity and schizophrenia, particularly during the transformative phase of adolescence when the brain undergoes significant changes. An abnormal balance between inhibition and excitation, influenced by GABAergic maturation deficits, connectivity disruptions, and altered perceptual information transfer, may contribute to the development of schizophrenia.This thesis offers valuable insights into the intricate mechanisms underlying schizophrenia, with a particular focus on the CTC circuit, NMDA receptors, and endocannabinoids in the context of neuronal plasticity and cognitive function

Neural Fields with Rebound Currents: Novel Routes to Patterning

The understanding of how spatio-temporal patterns of neural activity may arise in the cortex of the brain has advanced with the development and analysis of neural field models. To replicate this success for sub-cortical tissues, such as the thalamus, requires an extension to include relevant ionic currents that can further shape firing response. Here we advocate for one such approach that can accommodate slow currents. By way of illustration we focus on incorporating a T-type calcium current into the standard neural field framework. Direct numerical simulations are used to show that the resulting tissue model has many of the properties seen in more biophysically detailed model studies, and most importantly the generation of oscillations, waves, and patterns that arise from rebound firing. To explore the emergence of such solutions we focus on one-and two-dimensional spatial models and show that exact solutions describing homogeneous oscillations can be constructed n the limit that the firing rate nonlinearity is a Heaviside function. A linear stability analysis, using techniques from non-smooth dynamical systems, is used to determine the points at which bifurcations from synchrony can occur. Furthermore, we construct periodic travelling waves and investigate their stability with the use of an appropriate Evans function. The stable branches of the dispersion curve for periodic travelling waves are found to be in excellent agreement with simulations initiated from an unstable branch of the synchronous solution

Neural fields with rebound currents: Novel routes to patterning

The understanding of how spatio-temporal patterns of neural activity may arise in the cortex of the brain has advanced with the development and analysis of neural field models. Replicating this success for subcortical tissues, such as the thalamus, requires an extension to include relevant ionic currents that can further shape firing response. Here we advocate for one such approach that can accommodate slow currents. By way of illustration we focus on incorporating a T-type calcium current into the standard neural field framework. Direct numerical simulations are used to show that the resulting tissue model has many of the properties seen in more biophysically detailed model studies and, most important, the generation of oscillations, waves, and patterns that arise from rebound firing. To explore the emergence of such solutions we focus on one- and two-dimensional spatial models and show that exact solutions describing homogeneous oscillations can be constructed in the limit that the firing rate nonlinearity is a Heaviside function. A linear stability analysis, using techniques from nonsmooth dynamical systems, is used to determine the points at which bifurcations from synchrony can occur. Furthermore, we construct periodic traveling waves and investigate their stability with the use of an appropriate Evans function. The stable branches of the dispersion curve for periodic traveling waves are found to be in excellent agreement with simulations initiated from an unstable branch of the synchronous solution

Markov chain models of calcium puffs and sparks

Localized cytosolic Ca2+ elevations known as puffs and sparks are important regulators of cellular function that arise due to the cooperative activity of Ca2+-regulated inositol 1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RyRs) co-localized at Ca2+ release sites on the surface of the endoplasmic reticulum or sarcoplasmic reticulum. Theoretical studies have demonstrated that the cooperative gating of a cluster of Ca2+-regulated Ca 2+ channels modeled as a continuous-time discrete-state Markov chain may result in dynamics reminiscent of Ca2+ puffs and sparks. In such simulations, individual Ca2+-release channels are coupled via a mathematical representation of the local [Ca2+] and exhibit stochastic Ca2+ excitability where channels open and close in a concerted fashion. This dissertation uses Markov chain models of Ca 2+ release sites to advance our understanding of the biophysics connecting the microscopic parameters of IP3R and RyR gating to the collective phenomenon of puffs and sparks.;The dynamics of puffs and sparks exhibited by release site models that include both Ca2+ coupling and nearest-neighbor allosteric coupling are studied. Allosteric interactions are included in a manner that promotes the synchronous gating of channels by stabilizing neighboring closed-closed and/or open-open channel pairs. When the strength of Ca2+-mediated channel coupling is systematically varied, simulations that include allosteric interactions often exhibit more robust Ca2+ puffs and sparks. Interestingly, the changes in puff/spark duration, inter-event interval, and frequency observed upon the random removal of allosteric couplings that stabilize closed-closed channel pairs are qualitatively different than the changes observed when open-open channel pairs, or both open-open and closed-closed channel pairs are stabilized. The validity of a computationally efficient mean-field reduction applicable to the dynamics of a cluster of Ca2+-release Ca2+ channels coupled via the local [Ca2+] and allosteric interactions is also investigated.;Markov chain models of Ca2+ release sites composed of channels that are both activated and inactivated by Ca2+ are used to clarify the role of Ca2+ inactivation in the generation and termination of puffs and sparks. It is found that when the average fraction of inactivated channels is significant, puffs and sparks are often less sensitive to variations in the number of channels at release sites and the strength of Ca2+ coupling. While excessively fast Ca2+ inactivation can preclude puffs and sparks moderately fast Ca2+ inactivation often leads to time-irreversible puff/sparks whose termination is facilitated by the recruitment of inactivated channels throughout the duration of the puff/spark event. On the other hand, Ca2+ inactivation may be an important negative feedback mechanism even when its time constant is much greater than the duration of puffs and sparks. In fact, slow Ca 2+ inactivation can lead to release sites with a substantial fraction of inactivated channels that exhibit nearly time-reversible puffs and sparks that terminate without additional recruitment of inactivated channels

Characterization of response properties in the mouse lateral geniculate nucleus

The lateral geniculate nucleus (LGN) has been increasingly recognized to actively regulate information transmission to primary visual cortex (V1). Although efforts have been devoted to study its morphological and functional features, the full array of response characteristics in mouse LGN as well as their dependency on subjective state have been relatively unexplored. To address the question we recorded from mouse LGN with multisite-electrode-arrays (MEAs). From a dataset with 185 single units, our results revealed several exceptional response features in mouse LGN. We also demonstrated that subtypes, such as ON-/OFF-centre and transient/sustained cells exhibited functionally distinctive features, which might indicate parallel projections. To further compare response features from the full extent of mouse LGN, we developed a three-dimension (3D) LGN volume through histological approach. This volume explicitly captures morphological features of mouse LGN and provides the preciseness to classify location of single neuron into the anterior/middle/posterior LGN. Based on this categorization, we showed that response features were not regionally restricted within mouse LGN. We further examined neural activity with subjects in high or low isoflurane states. The distinct features in LFPs between the two states indicated that adjusting isoflurane concentration could provide a reliable and controllable experimental model to explore the state-dependent neural activity in mouse visual system. Subsequently, our results demonstrated that properties, including response latency, contrast sensitivity and spatial frequency properties were modulated by isoflurane concentration. Our current work suggests that mouse LGN can dynamically regulate information transmission to the cortex using numerous mechanisms, including responding mode, modulation of neuronal responses according to subjects’ states.Open Acces