1,075 research outputs found
Identifying Network Correlates of Memory Consolidation
Neuronal spiking activity carries information about our experiences in the waking world but exactly how the brain can quickly and efficiently encode sensory information into a useful neural code and then subsequently consolidate that information into memory remains a mystery. While neuronal networks are known to play a vital role in these processes, detangling the properties of network activity from the complex spiking dynamics observed is a formidable challenge, requiring collaborations across scientific disciplines. In this work, I outline my contributions in computational modeling and data analysis toward understanding how network dynamics facilitate memory consolidation. For experimental perspective, I investigate hippocampal recordings of mice that are subjected to contextual fear conditioning and subsequently undergo sleep-dependent fear memory consolidation. First, I outline the development of a functional connectivity algorithm which rapidly and robustly assesses network structure based on neuronal spike timing. I show that the relative stability of these functional networks can be used to identify global network dynamics, revealing that an increase in functional network stability correlates with successful fear memory consolidation in vivo. Using an attractor-based model to simulate memory encoding and consolidation, I go on to show that dynamics associated with a second-order phase transition, at a critical point in phase-space, are necessary for recruiting additional neurons into network dynamics associated with memory consolidation. I show that successful consolidation subsequently shifts dynamics away from a critical point and towards sub-critical dynamics. Investigations of in vivo spiking dynamics likewise revealed that hippocampal dynamics during non-rapid-eye-movement (NREM) sleep show features of being near a critical point and that fear memory consolidation leads to a shift in dynamics. Finally, I investigate the role of NREM sleep in facilitating memory consolidation using a conductance-based model of neuronal activity that can easily switch between modes of activity loosely representing waking and NREM sleep. Analysis of model simulations revealed that oscillations associated with NREM sleep promote a phase-based coding of information; neurons with high firing rates during periods of wake lead spiking activity during NREM oscillations. I show that when phase-coding is active in both simulations and in vivo, synaptic plasticity selectively strengthens the input to neurons firing late in the oscillation while simultaneously reducing input to neurons firing early in the oscillation. The effect is a net homogenization of firing rates observed in multiple other studies, and subsequently leads to recruitment of new neurons into a memory engram and information transfer from fast firing neurons to slow firing neurons. Taken together, my work outlines important, newly-discovered features of neuronal network dynamics related to memory encoding and consolidation: networks near criticality promote recruitment of additional neurons into stable firing patterns through NREM-associated oscillations and subsequently consolidates information into memories through phase-based coding.PHDBiophysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162991/1/qmskill_1.pd
Contributions to models of single neuron computation in striatum and cortex
A deeper understanding is required of how a single neuron utilizes its nonlinear subcellular devices to generate complex neuronal dynamics. Two compartmental models of cortex and striatum are accurately formulated and firmly grounded in the experimental reality of electrophysiology to address the questions: how striatal projection neurons implement location-dependent dendritic integration to carry out association-based computation and how cortical pyramidal neurons strategically exploit the type and location of synaptic contacts to enrich its computational capacities.Neuronale Zellen transformieren kontinuierliche Signale in diskrete Zeitserien von Aktionspotentialen und kodieren damit Perzeptionen und interne Zustände. Kompartiment-Modelle werden formuliert von Nervenzellen im Kortex und Striatum, die elektrophysiologisch fundiert sind, um spezifische Fragen zu adressieren: i) Inwiefern implementieren Projektionen vom Striatum ortsabhängige dendritische Integration, um Assoziationens-basierte Berechnungen zu realisieren? ii) Inwiefern nutzen kortikale Zellen den Typ und den Ort, um die durch sie realisierten Berechnungen zu optimieren
The influence of dopamine on prediction, action and learning
In this thesis I explore functions of the neuromodulator dopamine in the context
of autonomous learning and behaviour. I first investigate dopaminergic influence
within a simulated agent-based model, demonstrating how modulation of
synaptic plasticity can enable reward-mediated learning that is both adaptive and
self-limiting. I describe how this mechanism is driven by the dynamics of agentenvironment
interaction and consequently suggest roles for both complex spontaneous
neuronal activity and specific neuroanatomy in the expression of early, exploratory
behaviour. I then show how the observed response of dopamine neurons
in the mammalian basal ganglia may also be modelled by similar processes involving
dopaminergic neuromodulation and cortical spike-pattern representation within
an architecture of counteracting excitatory and inhibitory neural pathways, reflecting
gross mammalian neuroanatomy. Significantly, I demonstrate how combined
modulation of synaptic plasticity and neuronal excitability enables specific (timely)
spike-patterns to be recognised and selectively responded to by efferent neural populations,
therefore providing a novel spike-timing based implementation of the hypothetical
‘serial-compound’ representation suggested by temporal difference learning.
I subsequently discuss more recent work, focused upon modelling those complex
spike-patterns observed in cortex. Here, I describe neural features likely to contribute
to the expression of such activity and subsequently present novel simulation
software allowing for interactive exploration of these factors, in a more comprehensive
neural model that implements both dynamical synapses and dopaminergic
neuromodulation. I conclude by describing how the work presented ultimately suggests
an integrated theory of autonomous learning, in which direct coupling of agent
and environment supports a predictive coding mechanism, bootstrapped in early
development by a more fundamental process of trial-and-error learning
Self Organisation and Hierarchical Concept Representation in Networks of Spiking Neurons
The aim of this work is to introduce modular processing mechanisms for cortical functions implemented
in networks of spiking neurons. Neural maps are a feature of cortical processing
found to be generic throughout sensory cortical areas, and self-organisation to the fundamental
properties of input spike trains has been shown to be an important property of cortical organisation.
Additionally, oscillatory behaviour, temporal coding of information, and learning through
spike timing dependent plasticity are all frequently observed in the cortex. The traditional
self-organising map (SOM) algorithm attempts to capture the computational properties of this
cortical self-organisation in a neural network. As such, a cognitive module for a spiking SOM
using oscillations, phasic coding and STDP has been implemented. This model is capable of
mapping to distributions of input data in a manner consistent with the traditional SOM algorithm,
and of categorising generic input data sets. Higher-level cortical processing areas appear
to feature a hierarchical category structure that is founded on a feature-based object representation.
The spiking SOM model is therefore extended to facilitate input patterns in the form of
sets of binary feature-object relations, such as those seen in the field of formal concept analysis.
It is demonstrated that this extended model is capable of learning to represent the hierarchical
conceptual structure of an input data set using the existing learning scheme. Furthermore,
manipulations of network parameters allow the level of hierarchy used for either learning or
recall to be adjusted, and the network is capable of learning comparable representations when
trained with incomplete input patterns. Together these two modules provide related approaches
to the generation of both topographic mapping and hierarchical representation of input spaces
that can be potentially combined and used as the basis for advanced spiking neuron models of
the learning of complex representations
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Neuronal dynamics and connectivity analysis of neuronal cultures on multi electrode arrays
Despite a number of attempts over the past two decades, research into reliable, controlled induction of long term evoked responses, mimicking low level learning and memory in dissociated cell cultures remains challenging. In addition, a full understanding of the stimulus-response relationships that underlie synaptic plasticity has not yet been achieved, and many of the underlying principles remain largely unknown. Plasticity studies have been predominantly limited to low density Multi/Micro Electrode Arrays (MEAs). With the advent of complementary metal-oxide-semiconductor (CMOS) based High-Density (HD) MEAs, unprecedented spatial and temporal resolution is now possible. In this thesis, an attempt to bridge the gap between studies of neural plasticity and the use of CMOS based HD-MEAs with thousands of electrodes, is reported. Additionally, since such HD-MEAs generate a large volume of data and require advanced analytics to efficiently process and analyse recordings, computational tools and novel algorithms to infer connectivity during plasticity have been developed.
The study showed that the responsiveness, stability and initial firing rate of neuronal cultures are the deciding factors to reliably induce evoked responses. With multi-site stimulation, sustained long term potentiation was achieved, which was validated both by evoked response plots and overall firing rates measured at five different time points - before and after repeated stimulation, and at a three day time points. In contrast, while depression responses were observed, it was found that the effects were not sustained over many days. The findings of the study suggest that appropriate selection of neuronal cultures is crucial for inducing desired evoked responses and criteria for this have been developed. Furthermore, it is concluded that the initial responses to test stimuli can be used to determine whether potentiated or depressed responses are to be expected.
To analyse the recordings, pipeline of computational tools was developed. Firstly, neuronal synchrony metrics were adapted for the first time for large HD-MEA recordings and shown to correspond effectively to the firing dynamics. To analyse functional connectivity, an information theoretic approach, Transfer Entropy(TE), was utilised. The method showed accurate estimation of functional connectivity with mid 80th percentile accuracy on simulated data. A superimposition method was proposed to enhance confidence in the connectivity estimation. To statistically evaluate connectivity estimation, a new surrogate method, based on ISI distribution approach, was proposed and validated with a simulated Izhikevich network. The method achieved improved accuracy, compared to the existing ISI shuffling method. This newly developed method was later utilised to infer connectivity and refine connections during the learning process of real neuronal cultures over many days of stimulation. The connectivity inference corresponded accurately to both the spontaneous and stimulated networks during evoked responses and the proposed method permitted observation of the evolution of connections for the potentiated network
Single Biological Neurons as Temporally Precise Spatio-Temporal Pattern Recognizers
This PhD thesis is focused on the central idea that single neurons in the
brain should be regarded as temporally precise and highly complex
spatio-temporal pattern recognizers. This is opposed to the prevalent view of
biological neurons as simple and mainly spatial pattern recognizers by most
neuroscientists today. In this thesis, I will attempt to demonstrate that this
is an important distinction, predominantly because the above-mentioned
computational properties of single neurons have far-reaching implications with
respect to the various brain circuits that neurons compose, and on how
information is encoded by neuronal activity in the brain. Namely, that these
particular "low-level" details at the single neuron level have substantial
system-wide ramifications. In the introduction we will highlight the main
components that comprise a neural microcircuit that can perform useful
computations and illustrate the inter-dependence of these components from a
system perspective. In chapter 1 we discuss the great complexity of the
spatio-temporal input-output relationship of cortical neurons that are the
result of morphological structure and biophysical properties of the neuron. In
chapter 2 we demonstrate that single neurons can generate temporally precise
output patterns in response to specific spatio-temporal input patterns with a
very simple biologically plausible learning rule. In chapter 3, we use the
differentiable deep network analog of a realistic cortical neuron as a tool to
approximate the gradient of the output of the neuron with respect to its input
and use this capability in an attempt to teach the neuron to perform nonlinear
XOR operation. In chapter 4 we expand chapter 3 to describe extension of our
ideas to neuronal networks composed of many realistic biological spiking
neurons that represent either small microcircuits or entire brain regions
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