Publications
87 results found
Cayco-Gajic NA, Clopath C, Silver RA, 2017, Sparse synaptic connectivity is required for decorrelation and pattern separation in feedforward networks, Nature Communications, Vol: 8, ISSN: 2041-1723
Pattern separation is a fundamental function of the brain. The divergent feedforward networks thought to underlie this computation are widespread, yet exhibit remarkably similar sparse synaptic connectivity. Marr-Albus theory postulates that such networks separate overlapping activity patterns by mapping them onto larger numbers of sparsely active neurons. But spatial correlations in synaptic input and those introduced by network connectivity are likely to compromise performance. To investigate the structural and functional determinants of pattern separation we built models of the cerebellar input layer with spatially correlated input patterns, and systematically varied their synaptic connectivity. Performance was quantified by the learning speed of a classifier trained on either the input or output patterns. Our results show that sparse synaptic connectivity is essential for separating spatially correlated input patterns over a wide range of network activity, and that expansion and correlations, rather than sparse activity, are the major determinants of pattern separation.
Bono J, Clopath C, 2017, Modelling somatic and dendritic spike mediated plasticity at the single neuron and network level, Nature Communications, Vol: 8, ISSN: 2041-1723
Synaptic plasticity is thought to be the principal neuronal mechanism underlying learning. Models of plastic networks typically combine point neurons with spike-timing-dependent plasticity (STDP) as the learning rule. However, a point neuron does not capture the local non-linear processing of synaptic inputs allowed for by dendrites. Furthermore, experimental evidence suggests that STDP is not the only learning rule available to neurons. By implementing biophysically realistic neuron models, we study how dendrites enable multiple synaptic plasticity mechanisms to coexist in a single cell. In these models, we compare the conditions for STDP and for synaptic strengthening by local dendritic spikes. We also explore how the connectivity between two cells is affected by these plasticity rules and by different synaptic distributions. Finally, we show that how memory retention during associative learning can be prolonged in networks of neurons by including dendrites.
Bono J, Wilmes K, Clopath C, 2017, Modelling plasticity in dendrites: from single cells to networks, Current Opinion in Neurobiology, Vol: 46, Pages: 136-141, ISSN: 0959-4388
One of the key questions in neuroscience is how our brain self-organises to efficiently process information. To answer this question, we need to understand the underlying mechanisms of plasticity and their role in shaping synaptic connectivity. Theoretical neuroscience typically investigates plasticity on the level of neural networks. Neural network models often consist of point neurons, completely neglecting neuronal morphology for reasons of simplicity. However, during the past decades it became increasingly clear that inputs are locally processed in the dendrites before they reach the cell body. Dendritic properties enable local interactions between synapses and location-dependent modulations of inputs, rendering the position of synapses on dendrites highly important. These insights changed our view of neurons, such that we now think of them as small networks of nearly independent subunits instead of a simple point. Here, we propose that understanding how the brain processes information strongly requires that we consider the following properties: which plasticity mechanisms are present in the dendrites and how do they enable the self-organisation of synapses across the dendritic tree for efficient information processing? Ultimately, dendritic plasticity mechanisms can be studied in networks of neurons with dendrites, possibly uncovering unknown mechanisms that shape the connectivity in our brains.
Bass C, Helkkula P, De Paola V, et al., 2017, Detection of axonal synapses in 3D two-photon images, PLoS One, Vol: 12, Pages: 1-18, ISSN: 1932-6203
Studies of structural plasticity in the brain often require the detection and analysis of axonal synapses (boutons). To date, bouton detection has been largely manual or semi-automated, relying on a step that traces the axons before detection the boutons. If tracing the axon fails, the accuracy of bouton detection is compromised. In this paper, we propose a new algorithm that does not require tracing the axon to detect axonal boutons in 3D two-photon images taken from the mouse cortex. To find the most appropriate techniques for this task, we compared several well-known algorithms for interest point detection and feature descriptor generation. The final algorithm proposed has the following main steps: (1) a Laplacian of Gaussian (LoG) based feature enhancement module to accentuate the appearance of boutons; (2) a Speeded Up Robust Features (SURF) interest point detector to find candidate locations for feature extraction; (3) non-maximum suppression to eliminate candidates that were detected more than once in the same local region; (4) generation of feature descriptors based on Gabor filters; (5) a Support Vector Machine (SVM) classifier, trained on features from labelled data, and was used to distinguish between bouton and non-bouton candidates. We found that our method achieved a Recall of 95%, Precision of 76%, and F1 score of 84% within a new dataset that we make available for accessing bouton detection. On average, Recall and F1 score were significantly better than the current state-of-the-art method, while Precision was not significantly different. In conclusion, in this article we demonstrate that our approach, which is independent of axon tracing, can detect boutons to a high level of accuracy, and improves on the detection performance of existing approaches. The data and code (with an easy to use GUI) used in this article are available from open source repositories.
Hellyer P, Clopath C, Kehagia A, et al., 2017, From homeostasis to behavior: Balanced activity in an exploration of embodied dynamic environmental-neural interaction, PLoS Computational Biology, Vol: 13, ISSN: 1553-734X
In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we describe a simple model of spontaneous neural dynamics that controls an agent moving in a simple virtual environment. These dynamics generate interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics demonstrating the need for homeostatic mechanisms. We investigate roles for homeostatic plasticity both locally (local inhibition adjusting to balance excitatory input) as well as more globally (regional “task negative” activity that compensates for “task positive”, sensory input in another region) balancing neural activity and leading to more stable behavior (trajectories through the environment). Our results suggest complementary functional roles for both local and macroscale mechanisms in maintaining neural and behavioral dynamics and a novel functional role for macroscopic “task-negative” patterns of activity (e.g., the default mode network).
Brzosko Z, Zannone S, Schultz W, et al., 2017, Sequential neuromodulation of Hebbian plasticity offers mechanism for effective reward-based navigation, eLife, Vol: 6, Pages: 1-18, ISSN: 2050-084X
Spike timing-dependent plasticity (STDP) is under neuromodulatory control, which is correlated with distinct behavioral states. Previously we reported that dopamine, a reward signal, broadens the time window for synaptic potentiation and modulates the outcome of hippocampal STDP even when applied after the plasticity induction protocol (Brzosko et al., 2015). Here we demonstrate that sequential neuromodulation of STDP by acetylcholine and dopamine offers an efficacious model of reward-based navigation. Specifically, our experimental data in mouse hippocampal slices show that acetylcholine biases STDP towards synaptic depression, whilst subsequent application of dopamine converts this depression into potentiation. Incorporating this bidirectional neuromodulation-enabled correlational synaptic learning rule into a computational model yields effective navigation towards changing reward locations, as in natural foraging behavior. Thus, temporally sequenced neuromodulation of STDP enables associations to be made between actions and outcomes and also provides a possible mechanism for aligning the time scales of cellular and behavioral learning.
Clopath C, Bonhoeffer T, Hübener M, et al., 2017, Variance and Invariance of Neuronal Long-term Representations, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 372, ISSN: 1471-2970
Thebrainextractsbehaviorallyrelevantsensoryinputtoproduceappropriatemotoroutput.Ontheonehand,ourconstantlychangingenvironmentrequiresthistransformationtobeplastic.Ontheotherhand,plasticityisthoughttobebalancedbymechanismsensuringconstancyofneuronalrepresentationsinordertoachievestablebehavioralperformance.Yet,prominentchangesinsynapticstrengthandconnectivityalsooccurduringnormalsensoryexperience,indicatingacertaindegreeofconstitutiveplasticity.Thisraisesthequestionofhowstableneuronalrepresentationsareonthepopulationandalsoonthesingleneuronlevel.Herewereviewrecentdatafromlongitudinalelectrophysiologicalandopticalrecordingsofsingle-‐cellactivitythatassessthelong-‐termstabilityofneuronalstimulusselectivitiesunderconditionsofconstantsensoryexperience,duringlearning,andafterreversiblemodificationofsensoryinput.Theemergingpictureisthatneuronalrepresentationsarestabilizedbybehavioralrelevanceandthatthedegreeoflong-‐termtuningstabilityandperturbationresistancedirectlyrelatestothefunctionalroleoftherespectiveneurons,cell-‐types,andcircuits.Usinga‘toy’modelweshowthatstablebaselinerepresentationsandpreciserecoveryfromperturbationsinvisualcortexcouldarisefroma‘backbone’ofstrongrecurrentconnectivitybetweensimilarlytunedcellstogetherwithasmallnumberof‘anchor’neuronsexemptfromplasticchanges.
Pedrosa V, Clopath C, 2017, The role of neuromodulators in cortical lasticity. A computational perspective, Frontiers in Synaptic Neuroscience, Vol: 8, ISSN: 1663-3563
Neuromodulators play a ubiquitous role across the brain in regulating plasticity. With recent advances in experimental techniques, it is possible to study the effects of diverse neuromodulatory states in specific brain regions. Neuromodulators are thought to impact plasticity predominantly through two mechanisms: the gating of plasticity and the upregulation of neuronal activity. However, the consequences of these mechanisms are poorly understood and there is a need for both experimental and theoretical exploration. Here we illustrate how neuromodulatory state affects cortical plasticity through these two mechanisms. First, we explore the ability of neuromodulators to gate plasticity by reshaping the learning window for spike-timing-dependent plasticity. Using a simple computational model, we implement four different learning rules and demonstrate their effects on receptive field plasticity. We then compare the neuromodulatory effects of upregulating learning rate versus the effects of upregulating neuronal activity. We find that these seemingly similar mechanisms do not yield the same outcome: upregulating neuronal activity can lead to either a broadening or a sharpening of receptive field tuning, whereas upregulating learning rate only intensifies the sharpening of receptive field tuning. This simple model demonstrates the need for further exploration of the rich landscape of neuromodulator-mediated plasticity. Future experiments, coupled with biologically detailed computational models, will elucidate the diversity of mechanisms by which neuromodulatory state regulates cortical plasticity.
Badura A, Clopath C, Schonewille M, et al., 2016, Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments, Scientific Reports, Vol: 6, ISSN: 2045-2322
Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity.
Sweeney Y, Clopath C, 2016, Emergent spatial synaptic structure from diffusive plasticity, European Journal of Neuroscience, ISSN: 1460-9568
Some neurotransmitters can diffuse freely across cell membranes, influencing neighbouring neurons regardless of their synaptic coupling. This provides a means of neural communication, alternative to synaptic transmission, which can influence the way in which neural networks process information. Here, we ask whether diffusive neurotransmission can also influence the structure of synaptic connectivity in a network undergoing plasticity. We propose a form of Hebbian synaptic plasticity which is mediated by a diffusive neurotransmitter. Whenever a synapse is modified at an individual neuron through our proposed mechanism, similar but smaller modifications occur in synapses connecting to neighbouring neurons. The effects of this diffusive plasticity are explored in networks of rate-based neurons. This leads to the emergence of spatial structure in the synaptic connectivity of the network. We show that this spatial structure can coexist with other forms of structure in the synaptic connectivity, such as with groups of strongly interconnected neurons that form in response to correlated external drive. Finally, we explore diffusive plasticity in a simple feedforward network model of receptive field development. We show that, as widely observed across sensory cortex, the preferred stimulus identity of neurons in our network become spatially correlated due to diffusion. Our proposed mechanism of diffusive plasticity provides an efficient mechanism for generating these spatial correlations in stimulus preference which can flexibly interact with other forms of synaptic organisation.
Hellyer PJ, Jachs B, Clopath C, et al., 2015, Local inhibitory plasticity tunes macroscopic brain dynamics and allows the emergence of functional brain networks, Neuroimage, Vol: 124, Pages: 85-95, ISSN: 1095-9572
Rich, spontaneous brain activity has been observed across a range of different temporal and spatial scales. These dynamics are thought to be important for efficient neural functioning. A range of experimental evidence suggests that these neural dynamics are maintained across a variety of different cognitive states, in response to alterations of the environment and to changes in brain configuration (e.g., across individuals, development and in many neurological disorders). This suggests that the brain has evolved mechanisms to maintain rich dynamics across a broad range of situations. Several mechanisms based around homeostatic plasticity have been proposed to explain how these dynamics emerge from networks of neurons at the microscopic scale. Here we explore how a homeostatic mechanism may operate at the macroscopic scale: in particular, focusing on how it interacts with the underlying structural network topology and how it gives rise to well-described functional connectivity networks. We use a simple mean-field model of the brain, constrained by empirical white matter structural connectivity where each region of the brain is simulated using a pool of excitatory and inhibitory neurons. We show, as with the microscopic work, that homeostatic plasticity regulates network activity and allows for the emergence of rich, spontaneous dynamics across a range of brain configurations, which otherwise show a very limited range of dynamic regimes. In addition, the simulated functional connectivity of the homeostatic model better resembles empirical functional connectivity network. To accomplish this, we show how the inhibitory weights adapt over time to capture important graph theoretic properties of the underlying structural network. Therefore, this work presents suggests how inhibitory homeostatic mechanisms facilitate stable macroscopic dynamics to emerge in the brain, aiding the formation of functional connectivity networks.
Sadeh S, Clopath C, Rotter S, 2015, Processing of Feature Selectivity in Cortical Networks with Specific Connectivity (vol 10, e0127547, 2015), PLOS ONE, Vol: 10, ISSN: 1932-6203
Sadeh S, Clopath C, Rotter S, 2015, Emergence of Functional Specificity in Balanced Networks with Synaptic Plasticity, PLOS Computational Biology, Vol: 11, ISSN: 1553-734X
In rodent visual cortex, synaptic connections between orientation-selective neurons are unspecific at the time of eye opening, and become to some degree functionally specific only later during development. An explanation for this two-stage process was proposed in terms of Hebbian plasticity based on visual experience that would eventually enhance connections between neurons with similar response features. For this to work, however, two conditions must be satisfied: First, orientation selective neuronal responses must exist before specific recurrent synaptic connections can be established. Second, Hebbian learning must be compatible with the recurrent network dynamics contributing to orientation selectivity, and the resulting specific connectivity must remain stable for unspecific background activity. Previous studies have mainly focused on very simple models, where the receptive fields of neurons were essentially determined by feedforward mechanisms, and where the recurrent network was small, lacking the complex recurrent dynamics of large-scale networks of excitatory and inhibitory neurons. Here we studied the emergence of functionally specific connectivity in large-scale recurrent networks with synaptic plasticity. Our results show that balanced random networks, which already exhibit highly selective responses at eye opening, can develop feature-specific connectivity if appropriate rules of synaptic plasticity are invoked within and between excitatory and inhibitory populations. If these conditions are met, the initial orientation selectivity guides the process of Hebbian learning and, as a result, functionally specific and a surplus of bidirectional connections emerge. Our results thus demonstrate the cooperation of synaptic plasticity and recurrent dynamics in large-scale functional networks with realistic receptive fields, highlight the role of inhibition as a critical element in this process, and paves the road for further computational studies of sensory proc
Sadeh S, Clopath C, Rotter S, 2015, Processing of Feature Selectivity in Cortical Networks with Specific Connectivity, PLOS One, Vol: 10, ISSN: 1932-6203
Although non-specific at the onset of eye opening, networks in rodent visual cortex attain a non-random structure after eye opening, with a specific bias for connections between neurons of similar preferred orientations. As orientation selectivity is already present at eye opening, it remains unclear how this specificity in network wiring contributes to feature selectivity. Using large-scale inhibition-dominated spiking networks as a model, we show that feature-specific connectivity leads to a linear amplification of feedforward tuning, consistent with recent electrophysiological single-neuron recordings in rodent neocortex. Our results show that optimal amplification is achieved at an intermediate regime of specific connectivity. In this configuration a moderate increase of pairwise correlations is observed, consistent with recent experimental findings. Furthermore, we observed that feature-specific connectivity leads to the emergence of orientation-selective reverberating activity, and entails pattern completion in network responses. Our theoretical analysis provides a mechanistic understanding of subnetworks’ responses to visual stimuli, and casts light on the regime of operation of sensory cortices in the presence of specific connectivity.
Tchumatchenko T, Clopath C, 2014, Oscillations emerging from noise-driven steady state in networks with electrical synapses and subthreshold resonance, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723
- Author Web Link
- Cite
- Citations: 33
Clopath C, Badura A, De Zeeuw CI, et al., 2014, A Cerebellar Learning Model of Vestibulo-Ocular Reflex Adaptation in Wild-Type and Mutant Mice, JOURNAL OF NEUROSCIENCE, Vol: 34, Pages: 7203-7215, ISSN: 0270-6474
- Author Web Link
- Cite
- Citations: 36
Ko H, Cossell L, Baragli C, et al., 2013, The emergence of functional microcircuits in visual cortex, NATURE, Vol: 496, Pages: 96-+, ISSN: 0028-0836
- Author Web Link
- Open Access Link
- Cite
- Citations: 263
Clopath C, Brunel N, 2013, Optimal Properties of Analog Perceptrons with Excitatory Weights, PLOS COMPUTATIONAL BIOLOGY, Vol: 9
- Author Web Link
- Cite
- Citations: 20
Clopath C, 2012, Synaptic consolidation: an approach to long-term learning, COGNITIVE NEURODYNAMICS, Vol: 6, Pages: 251-257, ISSN: 1871-4080
- Author Web Link
- Cite
- Citations: 33
Clopath C, Nadal J-P, Brunel N, 2012, Storage of Correlated Patterns in Standard and Bistable Purkinje Cell Models, PLOS COMPUTATIONAL BIOLOGY, Vol: 8
- Author Web Link
- Cite
- Citations: 29
Vogels TP, Sprekeler H, Zenke F, et al., 2011, Inhibitory Plasticity Balances Excitation and Inhibition in Sensory Pathways and Memory Networks, SCIENCE, Vol: 334, Pages: 1569-1573, ISSN: 0036-8075
- Author Web Link
- Open Access Link
- Cite
- Citations: 389
Gjorgjieva J, Clopath C, Audet J, et al., 2011, A triplet spike-timing-dependent plasticity model generalizes the Bienenstock-Cooper-Munro rule to higher-order spatiotemporal correlations, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 19383-19388, ISSN: 0027-8424
- Author Web Link
- Open Access Link
- Cite
- Citations: 120
Clopath C, Buesing L, Vasilaki E, et al., 2010, Connectivity reflects coding: a model of voltage-based STDP with homeostasis, NATURE NEUROSCIENCE, Vol: 13, Pages: 344-U19, ISSN: 1097-6256
- Author Web Link
- Open Access Link
- Cite
- Citations: 380
Clopath C, Gerstner W, 2010, Voltage and Spike Timing Interact in STDP - A Unified Model., Front Synaptic Neurosci, Vol: 2
A phenomenological model of synaptic plasticity is able to account for a large body of experimental data on spike-timing-dependent plasticity (STDP). The basic ingredient of the model is the correlation of presynaptic spike arrival with postsynaptic voltage. The local membrane voltage is used twice: a first term accounts for the instantaneous voltage and the second one for a low-pass filtered voltage trace. Spike-timing effects emerge as a special case. We hypothesize that the voltage dependence can explain differential effects of STDP in dendrites, since the amplitude and time course of backpropagating action potentials or dendritic spikes influences the plasticity results in the model. The dendritic effects are simulated by variable choices of voltage time course at the site of the synapse, i.e., without an explicit model of the spatial structure of the neuron.
Clopath C, Ziegler L, Vasilaki E, et al., 2008, Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression, PLOS COMPUTATIONAL BIOLOGY, Vol: 4, ISSN: 1553-734X
- Author Web Link
- Cite
- Citations: 91
Naud R, Marcille N, Clopath C, et al., 2008, Firing patterns in the adaptive exponential integrate-and-fire model, BIOLOGICAL CYBERNETICS, Vol: 99, Pages: 335-347, ISSN: 0340-1200
- Author Web Link
- Cite
- Citations: 198
Clopath C, Jolivet R, Rauch A, et al., 2007, Predicting neuronal activity with simple models of the threshold type:: Adaptive Exponential Integrate-and-Fire model with two compartments, 15th Annual Computational Neuroscience Meeting, Publisher: ELSEVIER SCIENCE BV, Pages: 1668-1673, ISSN: 0925-2312
- Author Web Link
- Cite
- Citations: 47
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.