Clustering Predicts Memory Performance in Networks of Spiking and Non-Spiking Neurons

The problem we address in this paper is that of finding effective and parsimonious patterns of connectivity in sparse associative memories. This problem must be addressed in real neuronal systems, so that results in artificial systems could throw light on real systems. We show that there are efficient patterns of connectivity and that these patterns are effective in models with either spiking or non-spiking neurons. This suggests that there may be some underlying general principles governing good connectivity in such networks. We also show that the clustering of the network, measured by Clustering Coefficient, has a strong negative linear correlation to the performance of associative memory. This result is important since a purely static measure of network connectivity appears to determine an important dynamic property of the network

The Performance of Associative Memory Models with Biologically Inspired Connectivity

This thesis is concerned with one important question in artificial neural networks, that is, how biologically inspired connectivity of a network affects its associative memory performance. In recent years, research on the mammalian cerebral cortex, which has the main responsibility for the associative memory function in the brains, suggests that the connectivity of this cortical network is far from fully connected, which is commonly assumed in traditional associative memory models. It is found to be a sparse network with interesting connectivity characteristics such as the “small world network” characteristics, represented by short Mean Path Length, high Clustering Coefficient, and high Global and Local Efficiency. Most of the networks in this thesis are therefore sparsely connected. There is, however, no conclusive evidence of how these different connectivity characteristics affect the associative memory performance of a network. This thesis addresses this question using networks with different types of connectivity, which are inspired from biological evidences. The findings of this programme are unexpected and important. Results show that the performance of a non-spiking associative memory model is found to be predicted by its linear correlation with the Clustering Coefficient of the network, regardless of the detailed connectivity patterns. This is particularly important because the Clustering Coefficient is a static measure of one aspect of connectivity, whilst the associative memory performance reflects the result of a complex dynamic process. On the other hand, this research reveals that improvements in the performance of a network do not necessarily directly rely on an increase in the network’s wiring cost. Therefore it is possible to construct networks with high associative memory performance but relatively low wiring cost. Particularly, Gaussian distributed connectivity in a network is found to achieve the best performance with the lowest wiring cost, in all examined connectivity models. Our results from this programme also suggest that a modular network with an appropriate configuration of Gaussian distributed connectivity, both internal to each module and across modules, can perform nearly as well as the Gaussian distributed non-modular network. Finally, a comparison between non-spiking and spiking associative memory models suggests that in terms of associative memory performance, the implication of connectivity seems to transcend the details of the actual neural models, that is, whether they are spiking or non-spiking neurons

The Impact of Mild Traumatic Brain injury on Neuronal Networks and Neurobehavior

Despite its enormous incidence, mild traumatic brain injury is not well understood. One aspect that needs more definition is how the mechanical energy during injury affects neural circuit function. Recent developments in cellular imaging probes provide an opportunity to assess the dynamic state of neural networks with single-cell resolution. In this dissertation, we developed imaging methods to assess the state of dissociated cortical networks exposed to mild injury. We probed the microarchitecture of an injured cortical circuit subject to two different injury levels, mild stretch (10% peak) and mild/moderate (35%). We found that mild injury produced a transient increase in calcium activity that dissipated within 1 h after injury. Alternatively, mild/moderate mechanical injury produced immediate disruption in network synchrony, loss in excitatory tone, and increased modular topology, suggesting a threshold for repair and degradation. The more significant changes in network behavior at moderate stretch are influenced by NMDA receptor activation and subsequent proteolytic changes in the neuronal populations. With the ability to analyze individual neurons in a circuit before and after injury, we identified several biomarkers that confer increased risk or protection from mechanical injury. We found that pre-injury connectivity and NMDA receptor subtype composition (NR2A and NR2B content) are important predictors of node loss and remodeling. Mechanistically, stretch injury caused a reduction in voltage-dependent Mg2+ block of the NR2B-cotaning NMDA receptors, resulting in increased uncorrelated activity both at the single channel and network level. The reduced coincidence detection of the NMDA receptor and overactivation of these receptors further impaired network function and plasticity. Given the demonstrated link between NR2B-NMDARs and mitochondrial dysfunction, we discovered that neuronal de-integration from the network is mediated through mitochondrial signaling. Finally, we bridged these network level studies with an investigation of changes in neurobehavior following blast-induced traumatic brain injury (bTBI), a form of mild TBI. We first developed and validated an open-source toolbox for automating the scoring of several common behavior tasks to study the deficits that occur following bTBI. We then specifically evaluated the role of neuronal transcription factor Elk-1 in mediating deficits following blast by exposing Elk-1 knockout mouse to equivalent blast pressure loading. Our systems-level behavior analysis showed that bTBI creates a complex change in behavior, with an increase in anxiety and loss of habituation in object recognition. Moreover, we found these behavioral deficits were eliminated in Elk-1 knockout animals exposed to blast loading. Together, we merged information from different perspectives (in silico, in vitro, and in vivo) and length scales (single channels, single-cells, networks, and animals) to study the impact of mild traumatic brain injury on neuronal networks and neurobehavior

Functional connectivity and dendritic integration of feedback in visual cortex

A fundamental question in neuroscience is how different brain regions communicate with each other. Sensory processing engages distributed circuits across many brain areas and involves information flow in the feedforward and feedback direction. While feedforward processing is conceptually well understood, feedback processing has remained mysterious. Cortico-cortical feedback axons are enriched in layer 1, where they form synapses with the apical dendrites of pyramidal neurons. The organization and dendritic integration of information conveyed by these axons, however, are unknown. This thesis describes my efforts to link the circuit-level and dendritic-level organization of cortico-cortical feedback in the mouse visual system. First, using cellular resolution all-optical interrogation across cortical areas, I characterized the functional connectivity between the lateromedial higher visual area (LM) and primary visual cortex (V1). Feedback influence had both facilitating and suppressive effects on visually-evoked activity in V1 neurons, and was spatially organized: retinotopically aligned feedback was relatively more suppressive, while retinotopically offset feedback was relatively more facilitating. Second, to examine how feedback inputs are integrated in apical dendrites, I optogenetically stimulated presynaptic neurons in LM while using 2-photon calcium imaging to map feedback-recipient spines in the apical tufts of layer 5 neurons in V1. Activation of a single feedback-providing input was sufficient to boost calcium signals and recruit branch-specific local events in the recipient dendrite, suggesting that feedback can engage dendritic nonlinearities directly. Finally, I measured the recruitment of apical dendrites during visual stimulus processing. Surround visual stimuli, which should recruit relatively more facilitating feedback, drove local calcium events in apical tuft branches. Moreover, global dendritic event size was not purely determined by somatic activity but modulated by visual stimuli and behavioural state, in a manner consistent with the spatial organization of feedback. In summary, these results point toward a possible involvement of active dendritic processing in the integration of feedback signals. Active dendrites could thus provide a biophysical substrate for the integration of essential top-down information streams, including contextual or predictive processing

Relationship between brain plasticity, learning and foraging performance in honey bees.

Brain structure and learning capacities both vary with experience, but the mechanistic link between them is unclear. Here, we investigated whether experience-dependent variability in learning performance can be explained by neuroplasticity in foraging honey bees. The mushroom bodies (MBs) are a brain center necessary for ambiguous olfactory learning tasks such as reversal learning. Using radio frequency identification technology, we assessed the effects of natural variation in foraging activity, and the age when first foraging, on both performance in reversal learning and on synaptic connectivity in the MBs. We found that reversal learning performance improved at foraging onset and could decline with greater foraging experience. If bees started foraging before the normal age, as a result of a stress applied to the colony, the decline in learning performance with foraging experience was more severe. Analyses of brain structure in the same bees showed that the total number of synaptic boutons at the MB input decreased when bees started foraging, and then increased with greater foraging intensity. At foraging onset MB structure is therefore optimized for bees to update learned information, but optimization of MB connectivity deteriorates with foraging effort. In a computational model of the MBs sparser coding of information at the MB input improved reversal learning performance. We propose, therefore, a plausible mechanistic relationship between experience, neuroplasticity, and cognitive performance in a natural and ecological context

A Methodology for the Development of Recurrent Networks for Sequence Processing Tasks

Artificial neural networks are increasingly being used for dealing with real world applications. Many of these (e.g. speech recognition) are based on an ability to perform sequence processing. A class of artificial neural networks, known as recurrent networks, have architectures which incorporate feedback connections. This in turn allows the development of a memory mechanism to allow sequence processing to occur. A large number of recurrent network models have been developed, together with modifications of existing architectures and learning rules. However there has been comparatively little effort made to compare the performance of these models relative to each other. Such comparative studies would show differences in performance between networks and allow an examination of what features of a network give rise to desirable behaviours such as faster learning and superior generalisation ability. This thesis describes the results of a number of existing comparative studies and the results of new research. Three different recurrent networks, both in their original form and with modifications, are tested with four different sequence processing tasks. The results of this research clearly show that recurrent networks vary widely in terms of their performance and lead to a methodology based on the following conclusions: </br

Synaptic organisation of visual space in primary visual cortex

How a sensory stimulus is processed and perceived depends on the surrounding sensory scene. In the visual cortex, contextual signals can be conveyed by an extensive network of intra- and inter-areal excitatory connections that link neurons representing stimulus features separated in visual space. However, the connectional logic of visual contextual inputs remains unknown; it is not clear what information individual neurons receive from different parts of the visual field, nor how this input relates to the visual features a neuron encodes, defined by its spatial receptive field. We determined the organisation of excitatory synaptic inputs responding to different locations in the visual scene by mapping spatial receptive fields in dendritic spines of mouse visual cortex neurons using two-photon calcium imaging. We found that neurons received functionally diverse inputs from extended regions of visual space. Inputs representing similar visual features from the same location in visual space were more likely to cluster on neighbouring spines. Inputs from visual field regions beyond the postsynaptic neuron’s receptive field often synapsed on higher-order dendritic branches. These putative long-range inputs were more frequent and more likely to share the preference for oriented edges with the postsynaptic neuron when the input’s receptive field was spatially displaced along the axis of the postsynaptic neuron’s receptive field orientation. Therefore, the connectivity between neurons with displaced receptive fields obeys a specific rule, whereby they connect preferentially when their receptive fields are co-oriented and co-axially aligned. This organization of synaptic connectivity is ideally suited for amplification of elongated edges, which are enriched in the visual environment, and thus provides a potential substrate for contour integration and object grouping