Imperial College London

Dr Claudia Clopath

Faculty of EngineeringDepartment of Bioengineering

Professor of Computational Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 1435c.clopath Website

 
 
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Location

 

Royal School of Mines 4.09Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

40 results found

Wilten N, Clopath C, A diversity of interneurons and Hebbian plasticity facilitates rapid compressible learning in hippocampus, Nature Neuroscience, ISSN: 1097-6256

The hippocampus is able to rapidly learn incoming information, even if that information is only observedonce. Further, this information can be replayed in a compressed format in either forward or reverse modesduring Sharp Wave Ripples (SPW-Rs). We leveraged state-of-the-art techniques in training recurrent spikingnetworks to demonstrate how primarily interneuron networks can: 1) generate internal theta sequences tobind externally elicited spikes in the presence of inhibition from Medial Septum, 2) compress learned spikesequences in the form of a SPW-R when septal inhibition is removed, 3) generate and refine high-frequencyassemblies during SPW-R mediated compression, and 4) regulate the inter-ripple-interval timing betweenSPW-Rs in ripple clusters. From the fast timescale of neurons to the slow timescale of behaviours, interneuronnetworks serve as the scaffolding for one-shot learning by replaying, reversing, refining, and regulating spikesequences.

Journal article

Bono J, Clopath C, 2019, Synaptic plasticity onto inhibitory neurons as a mechanism for ocular dominance plasticity, PLOS COMPUTATIONAL BIOLOGY, Vol: 15

Journal article

Bouvierm G, Aljadeff J, Clopath C, Bimbard C, Ranft J, Blot A, Nadel J-P, Brunel N, Hakim V, Barbour Bet al., 2018, Cerebellar learning using perturbations, eLife, Vol: 7, ISSN: 2050-084X

The cerebellum aids the learning of fast, coordinated movements. According tocurrent consensus, erroneously active parallel fibre synapses are depressed by complex spikessignalling movement errors. However, this theory cannot solve the credit assignment problem ofprocessing a global movement evaluation into multiple cell-specific error signals. We identify apossible implementation of an algorithm solving this problem, whereby spontaneous complexspikes perturb ongoing movements, create eligibility traces and signal error changes guidingplasticity. Error changes are extracted by adaptively cancelling the average error. This framework,stochastic gradient descent with estimated global errors (SGDEGE), predicts synaptic plasticityrules that apparently contradict the current consensus but were supported by plasticityexperiments in slices from mice under conditions designed to be physiological, highlighting thesensitivity of plasticity studies to experimental conditions. We analyse the algorithm’s convergenceand capacity. Finally, we suggest SGDEGE may also operate in the basal ganglia.

Journal article

Nicola W, Hellyer PJ, Campbell SA, Clopath Cet al., 2018, Chaos in homeostatically regulated neural systems, Chaos, Vol: 28, ISSN: 1054-1500

Low-dimensional yet rich dynamics often emerge in the brain. Examples include oscillations and chaotic dynamics during sleep, epilepsy, and voluntary movement. However, a general mechanism for the emergence of low dimensional dynamics remains elusive. Here, we consider Wilson-Cowan networks and demonstrate through numerical and analytical work that homeostatic regulation of the network firing rates can paradoxically lead to a rich dynamical repertoire. The dynamics include mixed-mode oscillations, mixed-mode chaos, and chaotic synchronization when the homeostatic plasticity operates on a moderately slower time scale than the firing rates. This is true for a single recurrently coupled node, pairs of reciprocally coupled nodes without self-coupling, and networks coupled through experimentally determined weights derived from functional magnetic resonance imaging data. In all cases, the stability of the homeostatic set point is analytically determined or approximated. The dynamics at the network level are directly determined by the behavior of a single node system through synchronization in both oscillatory and non-oscillatory states. Our results demonstrate that rich dynamics can be preserved under homeostatic regulation or even be caused by homeostatic regulation.When recordings from the brain are analyzed, rich dynamics such as oscillations or low-dimensional chaos are often present. However, a general mechanism for how these dynamics emerge remains unresolved. Here, we explore the potential that these dynamics are caused by an interaction between synaptic homeostasis, and the connectivity between distinct populations of neurons. Using both analytical and numerical approaches, we analyze how data derived connection weights interact with inhibitory synaptic homeostasis to create rich dynamics such chaos and oscillations operating on multiple time scales. We demonstrate that these rich dynamical states are present in simple systems such as single population of neurons

Journal article

Zannone S, Brzosko Z, Paulsen O, Clopath Cet al., 2018, Acetylcholine-modulated plasticity in reward-driven navigation: a computational study, Scientific Reports, Vol: 8, ISSN: 2045-2322

Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules.

Journal article

Sollini J, Chapuis GA, Clopath C, Chadderton PTet al., 2018, ON-OFF receptive fields in auditory cortex diverge during development and contribute to directional sweep selectivity, Nature Communications, Vol: 9, ISSN: 2041-1723

Neurons in the auditory cortex exhibit distinct frequency tuning to the onset and offset of sounds, but the cause and significance of ON and OFF receptive field (RF) organisation are not understood. Here we demonstrate that distinct ON and OFF frequency tuning is largely absent in immature mouse auditory cortex and is thus a consequence of cortical development. Simulations using a novel implementation of a standard Hebbian plasticity model show that the natural alternation of sound onset and offset is sufficient for the formation of non-overlapping adjacent ON and OFF RFs in cortical neurons. Our model predicts that ON/OFF RF arrangement contributes towards direction selectivity to frequency-modulated tone sweeps, which we confirm by neuronal recordings. These data reveal that a simple and universally accepted learning rule can explain the organisation of ON and OFF RFs and direction selectivity in the developing auditory cortex.

Journal article

González Rueda A, Pedrosa V, Feord R, Clopath C, Paulsen Oet al., 2018, Activity dependent downscaling of subthreshold synaptic inputs during slow wave sleep like activity in vivo, Neuron, Vol: 97, Pages: 1244-1252.e5, ISSN: 0896-6273

Activity-dependent synaptic plasticity is critical for cortical circuit refinement. The synaptic homeostasis hypothesis suggests that synaptic connections are strengthened during wake and downscaled during sleep; however, it is not obvious how the same plasticity rules could explain both outcomes. Using whole-cell recordings and optogenetic stimulation of presynaptic input in urethane-anesthetized mice, which exhibit slow-wave-sleep (SWS)-like activity, we show that synaptic plasticity rules are gated by cortical dynamics in vivo. While Down states support conventional spike timing-dependent plasticity, Up states are biased toward depression such that presynaptic stimulation alone leads to synaptic depression, while connections contributing to postsynaptic spiking are protected against this synaptic weakening. We find that this novel activity-dependent and input-specific downscaling mechanism has two important computational advantages: (1) improved signal-to-noise ratio, and (2) preservation of previously stored information. Thus, these synaptic plasticity rules provide an attractive mechanism for SWS-related synaptic downscaling and circuit refinement.

Journal article

Pernelle G, Nicola W, Clopath C, 2018, Gap junction plasticity as a mechanism to regulate network-wide oscillations, PLoS Computational Biology, Vol: 14, ISSN: 1553-734X

Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex.

Journal article

Sammons RP, Clopath C, Barnes SJ, 2018, Size-dependent axonal bouton dynamics following visual deprivation in vivo, Cell Reports, Vol: 22, Pages: 576-584, ISSN: 2211-1247

Persistent synapses are thought to underpin the storage of sensory experience. Yet, little is known about their structural plasticity in vivo. We investigated how persistent presynaptic structures respond to the loss of primary sensory input. Using in vivo two-photon (2-P) imaging we measured fluctuations in the size of excitatory axonal boutons in L2/3 of adult mouse visual cortex after monocular enucleation. The average size of boutons did not change after deprivation, but the range of bouton sizes was reduced. Large boutons decreased and small boutons increased. Reduced bouton variance was accompanied by a reduced range of correlated calcium mediated neural activity in L2/3 of awake animals. Network simulations predicted that size-dependent plasticity may promote conditions of greater bidirectional plasticity. These predictions were supported by electrophysiological measures of short and long-term plasticity. We propose size-dependent dynamics facilitate cortical reorganization by maximising the potential for bidirectional plasticity.

Journal article

Kaplanis C, Shanahan M, Clopath C, 2018, Continual reinforcement learning with complex synapses, Pages: 3893-3902

© CURRAN-CONFERENCE. All rights reserved. Unlike humans, who are capable of continual learning over their lifetimes, artificial neural networks have long been known to suffer from a phenomenon known as catastrophic forgetting, whereby new learning can lead to abrupt erasure of previously acquired knowledge. Whereas in a neural network the parameters are typically modelled as scalar values, an individual synapse in the brain comprises a complex network of interacting biochemical components that evolve at different timescales. In this paper, we show that by equipping tabular and deep reinforcement learning agents with a synaptic model that incorporates this biological complexity (Benna & Fusi, 2016), catastrophic forgetting can be mitigated at multiple timescales. In particular, we find that as well as enabling continual learning across sequential training of two simple tasks, it can also be used to overcome within-task forgetting by reducing the need for an experience replay database.

Conference paper

Nicola W, Clopath C, 2017, Supervised Learning in Spiking Neural Networks with FORCE Training, Nature Communications, Vol: 8, ISSN: 2041-1723

Populations of neurons display an extraordinary diversity in the behaviors they affect and display. Machine learning techniques have recently emerged that allow us to create networks of model neurons that display behaviors of similar complexity. Here we demonstrate the direct applicability of one such technique, the FORCE method, to spiking neural networks. We train these networks to mimic dynamical systems, classify inputs, and store discrete sequences that correspond to the notes of a song. Finally, we use FORCE training to create two biologically motivated model circuits. One is inspired by the zebra finch and successfully reproduces songbird singing. The second network is motivated by the hippocampus and is trained to store and replay a movie scene. FORCE trained networks reproduce behaviors comparable in complexity to their inspired circuits and yield information not easily obtainable with other techniques, such as behavioral responses to pharmacological manipulations and spike timing statistics.

Journal article

Barnes, Franzoni E, Jacobsen RI, Erdelyi F, Szabo G, Clopath C, Keller GB, Keck Tet al., 2017, Deprivation-induced homeostatic spine scaling in vivo is localized to dendritic branches that have undergone recent spine loss, Neuron, Vol: 96, Pages: 871-882.e5, ISSN: 0896-6273

Synaptic scaling is a key homeostatic plasticity mechanism and is thought to be involved in the regulation of cortical activity levels. Here we investigated the spatial scale of homeostatic changes in spine size following sensory deprivation in a subset of inhibitory (layer 2/3 GAD65-positive) and excitatory (layer 5 Thy1-positive) neurons in mouse visual cortex. Using repeated in vivo two-photon imaging, we find that increases in spine size are tumor necrosis factor alpha (TNF-α) dependent and thus are likely associated with synaptic scaling. Rather than occurring at all spines, the observed increases in spine size are spatially localized to a subset of dendritic branches and are correlated with the degree of recent local spine loss within that branch. Using simulations, we show that such a compartmentalized form of synaptic scaling has computational benefits over cell-wide scaling for information processing within the cell.

Journal article

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.

Journal article

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.

Journal article

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.

Journal article

Bass C, Helkkula P, De Paola V, Clopath C, Bharath AAet al., 2017, Detection of axonal synapses in 3D two-photon images., PLoS ONE, Vol: 12, 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.

Journal article

Hellyer P, Clopath C, Kehagia A, Turkheimer FE, Leech Ret 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).

Journal article

Brzosko Z, Zannone S, Schultz W, Clopath C, Paulsen Oet al., 2017, Sequential neuromodulation of Hebbian plasticity offers mechanism for effective reward-based navigation., eLife, Vol: 6, 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.

Journal article

Kirkpatrick J, Pascanu R, Rabinowitz N, Veness J, Desjardins G, Rusu AA, Milan K, Quan J, Ramalho T, Grabska-Barwinska A, Hassabis D, Clopath C, Kumaran D, Hadsell Ret al., Overcoming catastrophic forgetting in neural networks, Proceedings of the National Academy of Sciences of the United States of America, ISSN: 1091-6490

The ability to learn tasks in a sequential fashion is crucial to the developmentof artificial intelligence. Until now neural networks havenot been capable of this and it has been widely thought that catastrophicforgetting is an inevitable feature of connectionist models.We show that it is possible to overcome this limitation and train networksthat can maintain expertise on tasks which they have not experiencedfor a long time. Our approach remembers old tasks by selectivelyslowing down learning on the weights important for thosetasks. We demonstrate our approach is scalable and effective bysolving a set of classification tasks based on the MNIST hand writtendigit dataset and by learning several Atari 2600 games sequentially.

Journal article

Clopath C, Bonhoeffer T, Hübener M, Rose Tet 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.

Journal article

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.

Journal article

Badura A, Clopath C, Schonewille M, De Zeeuw CIet 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.

Journal article

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.

Journal article

Hellyer PJ, Jachs B, Clopath C, Leech Ret 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.

Journal article

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

Journal article

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

Journal article

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.

Journal article

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

Journal article

Clopath C, Badura A, De Zeeuw CI, Brunel Net 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

Journal article

Ko H, Cossell L, Baragli C, Antolik J, Clopath C, Hofer SB, Mrsic-Flogel TDet al., 2013, The emergence of functional microcircuits in visual cortex, NATURE, Vol: 496, Pages: 96-+, ISSN: 0028-0836

Journal article

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