Dynamic Control of Network Level Information Processing through Cholinergic Modulation

Acetylcholine (ACh) release is a prominent neurochemical marker of arousal state within the brain. Changes in ACh are associated with changes in neural activity and information processing, though its exact role and the mechanisms through which it acts are unknown. Here I show that the dynamic changes in ACh levels that are associated with arousal state control informational processing functions of networks through its effects on the degree of Spike-Frequency Adaptation (SFA), an activity dependent decrease in excitability, synchronizability, and neuronal resonance displayed by single cells. Using numerical modeling I develop mechanistic explanations for how control of these properties shift network activity from a stable high frequency spiking pattern to a traveling wave of activity. This transition mimics the change in brain dynamics seen between high ACh states, such as waking and Rapid Eye Movement (REM) sleep, and low ACh states such as Non-REM (NREM) sleep. A corresponding, and related, transition in network level memory recall is also occurs as ACh modulates neuronal SFA. When ACh is at its highest levels (waking) all memories are stably recalled, as ACh is decreased (REM) in the model weakly encoded memories destabilize while strong memories remain stable. In levels of ACh that match Slow Wave Sleep (SWS), no encoded memories are stably recalled. This results from a competition between SFA and excitatory input strength and provides a mechanism for neural networks to control the representation of underlying synaptic information. Finally I show that during the low ACh conditions, oscillatory conditions allow for external inputs to be properly stored in and recalled from synaptic weights. Taken together this work demonstrates that dynamic neuromodulation is critical for the regulation of information processing tasks in neural networks. These results suggest that ACh is capable of switching networks between two distinct information processing modes. Rate coding of information is facilitated during high ACh conditions and phase coding of information is facilitated during low ACh conditions. Finally I propose that ACh levels control whether a network is in one of three functional states: (High ACh; Active waking) optimized for encoding of new information or the stable representation of relevant memories, (Mid ACh; resting state or REM) optimized for encoding connections between currently stored memories or searching the catalog of stored memories, and (Low ACh; NREM) optimized for renormalization of synaptic strength and memory consolidation. This work provides a mechanistic insight into the role of dynamic changes in ACh levels for the encoding, consolidation, and maintenance of memories within the brain.PHDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147503/1/roachjp_1.pd

Neural Avalanches at the Critical Point between Replay and Non-Replay of Spatiotemporal Patterns

We model spontaneous cortical activity with a network of coupled spiking units, in which multiple spatio-temporal patterns are stored as dynamical attractors. We introduce an order parameter, which measures the overlap (similarity) between the activity of the network and the stored patterns. We find that, depending on the excitability of the network, different working regimes are possible. For high excitability, the dynamical attractors are stable, and a collective activity that replays one of the stored patterns emerges spontaneously, while for low excitability, no replay is induced. Between these two regimes, there is a critical region in which the dynamical attractors are unstable, and intermittent short replays are induced by noise. At the critical spiking threshold, the order parameter goes from zero to one, and its fluctuations are maximized, as expected for a phase transition (and as observed in recent experimental results in the brain). Notably, in this critical region, the avalanche size and duration distributions follow power laws. Critical exponents are consistent with a scaling relationship observed recently in neural avalanches measurements. In conclusion, our simple model suggests that avalanche power laws in cortical spontaneous activity may be the effect of a network at the critical point between the replay and non-replay of spatio-temporal patterns

Representational Switching by Dynamical Reorganization of Attractor Structure in a Network Model of the Prefrontal Cortex

The prefrontal cortex (PFC) plays a crucial role in flexible cognitive behavior by representing task relevant information with its working memory. The working memory with sustained neural activity is described as a neural dynamical system composed of multiple attractors, each attractor of which corresponds to an active state of a cell assembly, representing a fragment of information. Recent studies have revealed that the PFC not only represents multiple sets of information but also switches multiple representations and transforms a set of information to another set depending on a given task context. This representational switching between different sets of information is possibly generated endogenously by flexible network dynamics but details of underlying mechanisms are unclear. Here we propose a dynamically reorganizable attractor network model based on certain internal changes in synaptic connectivity, or short-term plasticity. We construct a network model based on a spiking neuron model with dynamical synapses, which can qualitatively reproduce experimentally demonstrated representational switching in the PFC when a monkey was performing a goal-oriented action-planning task. The model holds multiple sets of information that are required for action planning before and after representational switching by reconfiguration of functional cell assemblies. Furthermore, we analyzed population dynamics of this model with a mean field model and show that the changes in cell assemblies' configuration correspond to those in attractor structure that can be viewed as a bifurcation process of the dynamical system. This dynamical reorganization of a neural network could be a key to uncovering the mechanism of flexible information processing in the PFC

The Timing of Vision – How Neural Processing Links to Different Temporal Dynamics

In this review, we describe our recent attempts to model the neural correlates of visual perception with biologically inspired networks of spiking neurons, emphasizing the dynamical aspects. Experimental evidence suggests distinct processing modes depending on the type of task the visual system is engaged in. A first mode, crucial for object recognition, deals with rapidly extracting the glimpse of a visual scene in the first 100 ms after its presentation. The promptness of this process points to mainly feedforward processing, which relies on latency coding, and may be shaped by spike timing-dependent plasticity (STDP). Our simulations confirm the plausibility and efficiency of such a scheme. A second mode can be engaged whenever one needs to perform finer perceptual discrimination through evidence accumulation on the order of 400 ms and above. Here, our simulations, together with theoretical considerations, show how predominantly local recurrent connections and long neural time-constants enable the integration and build-up of firing rates on this timescale. In particular, we review how a non-linear model with attractor states induced by strong recurrent connectivity provides straightforward explanations for several recent experimental observations. A third mode, involving additional top-down attentional signals, is relevant for more complex visual scene processing. In the model, as in the brain, these top-down attentional signals shape visual processing by biasing the competition between different pools of neurons. The winning pools may not only have a higher firing rate, but also more synchronous oscillatory activity. This fourth mode, oscillatory activity, leads to faster reaction times and enhanced information transfers in the model. This has indeed been observed experimentally. Moreover, oscillatory activity can format spike times and encode information in the spike phases with respect to the oscillatory cycle. This phenomenon is referred to as “phase-of-firing coding,” and experimental evidence for it is accumulating in the visual system. Simulations show that this code can again be efficiently decoded by STDP. Future work should focus on continuous natural vision, bio-inspired hardware vision systems, and novel experimental paradigms to further distinguish current modeling approaches

Associative memory of phase-coded spatiotemporal patterns in leaky Integrate and Fire networks

We study the collective dynamics of a Leaky Integrate and Fire network in which precise relative phase relationship of spikes among neurons are stored, as attractors of the dynamics, and selectively replayed at differentctime scales. Using an STDP-based learning process, we store in the connectivity several phase-coded spike patterns, and we find that, depending on the excitability of the network, different working regimes are possible, with transient or persistent replay activity induced by a brief signal. We introduce an order parameter to evaluate the similarity between stored and recalled phase-coded pattern, and measure the storage capacity. Modulation of spiking thresholds during replay changes the frequency of the collective oscillation or the number of spikes per cycle, keeping preserved the phases relationship. This allows a coding scheme in which phase, rate and frequency are dissociable. Robustness with respect to noise and heterogeneity of neurons parameters is studied, showing that, since dynamics is a retrieval process, neurons preserve stablecprecise phase relationship among units, keeping a unique frequency of oscillation, even in noisy conditions and with heterogeneity of internal parameters of the units

Metastability, Criticality and Phase Transitions in brain and its Models

This essay extends the previously deposited paper "Oscillations, Metastability and Phase Transitions" to incorporate the theory of Self-organizing Criticality. The twin concepts of Scaling and Universality of the theory of nonequilibrium phase transitions is applied to the role of reentrant activity in neural circuits of cerebral cortex and subcortical neural structures

Investigating the role of fast-spiking interneurons in neocortical dynamics

PhD ThesisFast-spiking interneurons are the largest interneuronal population in neocortex. It is well documented that this population is crucial in many functions of the neocortex by subserving all aspects of neural computation, like gain control, and by enabling dynamic phenomena, like the generation of high frequency oscillations. Fast-spiking interneurons, which represent mainly the parvalbumin-expressing, soma-targeting basket cells, are also implicated in pathological dynamics, like the propagation of seizures or the impaired coordination of activity in schizophrenia. In the present thesis, I investigate the role of fast-spiking interneurons in such dynamic phenomena by using computational and experimental techniques. First, I introduce a neural mass model of the neocortical microcircuit featuring divisive inhibition, a gain control mechanism, which is thought to be delivered mainly by the soma-targeting interneurons. Its dynamics were analysed at the onset of chaos and during the phenomena of entrainment and long-range synchronization. It is demonstrated that the mechanism of divisive inhibition reduces the sensitivity of the network to parameter changes and enhances the stability and exibility of oscillations. Next, in vitro electrophysiology was used to investigate the propagation of activity in the network of electrically coupled fast-spiking interneurons. Experimental evidence suggests that these interneurons and their gap junctions are involved in the propagation of seizures. Using multi-electrode array recordings and optogenetics, I investigated the possibility of such propagating activity under the conditions of raised extracellular K+ concentration which applies during seizures. Propagated activity was recorded and the involvement of gap junctions was con rmed by pharmacological manipulations. Finally, the interaction between two oscillations was investigated. Two oscillations with di erent frequencies were induced in cortical slices by directly activating the pyramidal cells using optogenetics. Their interaction suggested the possibility of a coincidence detection mechanism at the circuit level. Pharmacological manipulations were used to explore the role of the inhibitory interneurons during this phenomenon. The results, however, showed that the observed phenomenon was not a result of synaptic activity. Nevertheless, the experiments provided some insights about the excitability of the tissue through scattered light while using optogenetics. This investigation provides new insights into the role of fast-spiking interneurons in the neocortex. In particular, it is suggested that the gain control mechanism is important for the physiological oscillatory dynamics of the network and that the gap junctions between these interneurons can potentially contribute to the inhibitory restraint during a seizure.Wellcome Trust

Dynamical principles in neuroscience

Dynamical modeling of neural systems and brain functions has a history of success over the last half century. This includes, for example, the explanation and prediction of some features of neural rhythmic behaviors. Many interesting dynamical models of learning and memory based on physiological experiments have been suggested over the last two decades. Dynamical models even of consciousness now exist. Usually these models and results are based on traditional approaches and paradigms of nonlinear dynamics including dynamical chaos. Neural systems are, however, an unusual subject for nonlinear dynamics for several reasons: (i) Even the simplest neural network, with only a few neurons and synaptic connections, has an enormous number of variables and control parameters. These make neural systems adaptive and flexible, and are critical to their biological function. (ii) In contrast to traditional physical systems described by well-known basic principles, first principles governing the dynamics of neural systems are unknown. (iii) Many different neural systems exhibit similar dynamics despite having different architectures and different levels of complexity. (iv) The network architecture and connection strengths are usually not known in detail and therefore the dynamical analysis must, in some sense, be probabilistic. (v) Since nervous systems are able to organize behavior based on sensory inputs, the dynamical modeling of these systems has to explain the transformation of temporal information into combinatorial or combinatorial-temporal codes, and vice versa, for memory and recognition. In this review these problems are discussed in the context of addressing the stimulating questions: What can neuroscience learn from nonlinear dynamics, and what can nonlinear dynamics learn from neuroscience?This work was supported by NSF Grant No. NSF/EIA-0130708, and Grant No. PHY 0414174; NIH Grant No. 1 R01 NS50945 and Grant No. NS40110; MEC BFI2003-07276, and Fundación BBVA

Spiking Dynamics during Perceptual Grouping in the Laminar Circuits of Visual Cortex

Grouping of collinear boundary contours is a fundamental process during visual perception. Illusory contour completion vividly illustrates how stable perceptual boundaries interpolate between pairs of contour inducers, but do not extrapolate from a single inducer. Neural models have simulated how perceptual grouping occurs in laminar visual cortical circuits. These models predicted the existence of grouping cells that obey a bipole property whereby grouping can occur inwardly between pairs or greater numbers of similarly oriented and co-axial inducers, but not outwardly from individual inducers. These models have not, however, incorporated spiking dynamics. Perceptual grouping is a challenge for spiking cells because its properties of collinear facilitation and analog sensitivity to inducer configurations occur despite irregularities in spike timing across all the interacting cells. Other models have demonstrated spiking dynamics in laminar neocortical circuits, but not how perceptual grouping occurs. The current model begins to unify these two modeling streams by implementing a laminar cortical network of spiking cells whose intracellular temporal dynamics interact with recurrent intercellular spiking interactions to quantitatively simulate data from neurophysiological experiments about perceptual grouping, the structure of non-classical visual receptive fields, and gamma oscillations.CELEST, an NSF Science of Learning Center (SBE-0354378); SyNAPSE program of the Defense Advanced Research Project Agency (HR001109-03-0001); Defense Advanced Research Project Agency (HR001-09-C-0011