Publications
89 results found
Prince LY, Bacon T, Humphries R, et al., 2021, Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits, PLoS Computational Biology, Vol: 17, Pages: 1-37, ISSN: 1553-734X
In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.
Kaleb K, Pedrosa V, Clopath C, 2021, Network-centered homeostasis through inhibition maintains hippocampal spatial map and cortical circuit function, CELL REPORTS, Vol: 36, ISSN: 2211-1247
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- Citations: 5
Gogianu F, Berariu T, Rosca M, et al., 2021, Spectral normalisation for deep reinforcement learning: an optimisation perspective, International Conference on Machine Learning (ICML), Publisher: JMLR-JOURNAL MACHINE LEARNING RESEARCH, Pages: 1-11, ISSN: 2640-3498
Most of the recent deep reinforcement learningadvances take an RL-centric perspective and focus on refinements of the training objective. Wediverge from this view and show we can recoverthe performance of these developments not bychanging the objective, but by regularising thevalue-function estimator. Constraining the Lipschitz constant of a single layer using spectralnormalisation is sufficient to elevate the performance of a Categorical-DQN agent to that of amore elaborated RAINBOW agent on the challenging Atari domain. We conduct ablation studiesto disentangle the various effects normalisationhas on the learning dynamics and show that issufficient to modulate the parameter updates torecover most of the performance of spectral normalisation. These findings hint towards the needto also focus on the neural component and itslearning dynamics to tackle the peculiarities ofDeep Reinforcement Learning.
Ang GWY, Tang CS, Hay YA, et al., 2021, The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning, PLoS Computational Biology, Vol: 17, Pages: 1-22, ISSN: 1553-734X
To survive, animals have to quickly modify their behaviour when the reward changes. The internal representations responsible for this are updated through synaptic weight changes, mediated by certain neuromodulators conveying feedback from the environment. In previous experiments, we discovered a form of hippocampal Spike-Timing-Dependent-Plasticity (STDP) that is sequentially modulated by acetylcholine and dopamine. Acetylcholine facilitates synaptic depression, while dopamine retroactively converts the depression into potentiation. When these experimental findings were implemented as a learning rule in a computational model, our simulations showed that cholinergic-facilitated depression is important for reversal learning. In the present study, we tested the model’s prediction by optogenetically inactivating cholinergic neurons in mice during a hippocampus-dependent spatial learning task with changing rewards. We found that reversal learning, but not initial place learning, was impaired, verifying our computational prediction that acetylcholine-modulated plasticity promotes the unlearning of old reward locations. Further, differences in neuromodulator concentrations in the model captured mouse-by-mouse performance variability in the optogenetic experiments. Our line of work sheds light on how neuromodulators enable the learning of new contingencies.
Maes A, Barahona M, Clopath C, 2021, Learning compositional sequences with multiple time scales through a hierarchical network of spiking neurons, PLoS Computational Biology, Vol: 17, ISSN: 1553-734X
Sequential behaviour is often compositional and organised across multiple time scales: a set of individual elements developing on short time scales (motifs) are combined to form longer functional sequences (syntax). Such organisation leads to a natural hierarchy that can be used advantageously for learning, since the motifs and the syntax can be acquired independently. Despite mounting experimental evidence for hierarchical structures in neuroscience, models for temporal learning based on neuronal networks have mostly focused on serial methods. Here, we introduce a network model of spiking neurons with a hierarchical organisation aimed at sequence learning on multiple time scales. Using biophysically motivated neuron dynamics and local plasticity rules, the model can learn motifs and syntax independently. Furthermore, the model can relearn sequences efficiently and store multiple sequences. Compared to serial learning, the hierarchical model displays faster learning, more flexible relearning, increased capacity, and higher robustness to perturbations. The hierarchical model redistributes the variability: it achieves high motif fidelity at the cost of higher variability in the between-motif timings.
Zenke F, Bohté SM, Clopath C, et al., 2021, Visualizing a joint future of neuroscience and neuromorphic engineering, Neuron, Vol: 109, Pages: 571-575, ISSN: 0896-6273
Recent research resolves the challenging problem of building biophysically plausible spiking neural models that are also capable of complex information processing. This advance creates new opportunities in neuroscience and neuromorphic engineering, which we discussed at an online focus meeting.
Feulner B, Clopath C, 2021, Neural manifold under plasticity in a goal driven learning behaviour, PLoS Computational Biology, Vol: 17, Pages: 1-27, ISSN: 1553-734X
Neural activity is often low dimensional and dominated by only a few prominent neural covariation patterns. It has been hypothesised that these covariation patterns could form the building blocks used for fast and flexible motor control. Supporting this idea, recent experiments have shown that monkeys can learn to adapt their neural activity in motor cortex on a timescale of minutes, given that the change lies within the original low-dimensional subspace, also called neural manifold. However, the neural mechanism underlying this within-manifold adaptation remains unknown. Here, we show in a computational model that modification of recurrent weights, driven by a learned feedback signal, can account for the observed behavioural difference between within- and outside-manifold learning. Our findings give a new perspective, showing that recurrent weight changes do not necessarily lead to change in the neural manifold. On the contrary, successful learning is naturally constrained to a common subspace.
Sadeh S, Clopath C, 2020, Inhibitory stabilization and cortical computation, Nature Reviews Neuroscience, ISSN: 1471-003X
Sadeh S, Clopath C, 2020, Theory of neuronal perturbome in cortical networks., Proceedings of the National Academy of Sciences of USA, Vol: 117, Pages: 26966-26976, ISSN: 0027-8424
To unravel the functional properties of the brain, we need to untangle how neurons interact with each other and coordinate in large-scale recurrent networks. One way to address this question is to measure the functional influence of individual neurons on each other by perturbing them in vivo. Application of such single-neuron perturbations in mouse visual cortex has recently revealed feature-specific suppression between excitatory neurons, despite the presence of highly specific excitatory connectivity, which was deemed to underlie feature-specific amplification. Here, we studied which connectivity profiles are consistent with these seemingly contradictory observations, by modeling the effect of single-neuron perturbations in large-scale neuronal networks. Our numerical simulations and mathematical analysis revealed that, contrary to the prima facie assumption, neither inhibition dominance nor broad inhibition alone were sufficient to explain the experimental findings; instead, strong and functionally specific excitatory-inhibitory connectivity was necessary, consistent with recent findings in the primary visual cortex of rodents. Such networks had a higher capacity to encode and decode natural images, and this was accompanied by the emergence of response gain nonlinearities at the population level. Our study provides a general computational framework to investigate how single-neuron perturbations are linked to cortical connectivity and sensory coding and paves the road to map the perturbome of neuronal networks in future studies.
Udakis M, Pedrosa V, Chamberlain SEL, et al., 2020, Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output, Nature Communications, Vol: 11, Pages: 4395-4395, ISSN: 2041-1723
The formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.
Pedrosa V, Clopath C, 2020, The interplay between somatic and dendritic inhibition promotes the emergence and stabilization of place fields, PLoS Computational Biology, Vol: 16, ISSN: 1553-734X
During the exploration of novel environments, place fields are rapidly formed in hippocampal CA1 neurons. Place cell firing rate increases in early stages of exploration of novel environments but returns to baseline levels in familiar environments. Although similar in amplitude and width, place fields in familiar environments are more stable than in novel environments. We propose a computational model of the hippocampal CA1 network, which describes the formation, dynamics and stabilization of place fields. We show that although somatic disinhibition is sufficient to form place fields, dendritic inhibition along with synaptic plasticity is necessary for place field stabilization. Our model suggests that place cell stability can be attributed to strong excitatory synaptic weights and strong dendritic inhibition. We show that the interplay between somatic and dendritic inhibition balances the increased excitatory weights, such that place cells return to their baseline firing rate after exploration. Our model suggests that different types of interneurons are essential to unravel the mechanisms underlying place field plasticity. Finally, we predict that artificially induced dendritic events can shift place fields even after place field stabilization.
Tomasev N, Cornebise J, Hutter F, et al., 2020, AI for social good: unlocking the opportunity for positive impact, NATURE COMMUNICATIONS, Vol: 11
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- Citations: 66
Clopath C, Sweeney YA, 2020, Population coupling predicts the plasticity of stimulus responses in cortical circuits, eLife, Vol: 9, ISSN: 2050-084X
Some neurons have stimulus responses that are stable over days, whereas other neurons have highly plastic stimulus responses. Using a recurrent network model, we explore whether this could be due to an underlying diversity in their synaptic plasticity. We find that, in a network with diverse learning rates, neurons with fast rates are more coupled to population activity than neurons with slow rates. This plasticity-coupling link predicts that neurons with high population coupling exhibit more long-term stimulus response variability than neurons with low population coupling. We substantiate this prediction using recordings from the Allen Brain Observatory, finding that a neuron’s population coupling is correlated with the plasticity of its orientation preference. Simulations of a simple perceptual learning task suggest a particular functional architecture: a stable ‘backbone’ of stimulus representation formed by neurons with low population coupling, on top of which lies a flexible substrate of neurons with high population coupling.
Sadeh S, Clopath C, 2020, Patterned perturbation of inhibition can reveal the dynamical structure of neural processing, eLife, Vol: 9, ISSN: 2050-084X
Perturbation of neuronal activity is key to understanding the brain's functional properties, however, intervention studies typically perturb neurons in a nonspecific manner. Recent optogenetics techniques have enabled patterned perturbations, in which specific patterns of activity can be invoked in identified target neurons to reveal more specific cortical function. Here, we argue that patterned perturbation of neurons is in fact necessary to reveal the specific dynamics of inhibitory stabilization, emerging in cortical networks with strong excitatory and inhibitory functional subnetworks, as recently reported in mouse visual cortex. We propose a specific perturbative signature of these networks and investigate how this can be measured under different experimental conditions. Functionally, rapid spontaneous transitions between selective ensembles of neurons emerge in such networks, consistent with experimental results. Our study outlines the dynamical and functional properties of feature-specific inhibitory-stabilized networks, and suggests experimental protocols that can be used to detect them in the intact cortex.
Maes A, Barahona M, Clopath C, 2020, Learning spatiotemporal signals using a recurrent spiking network that discretizes time, PLoS Computational Biology, Vol: 16, Pages: 1-26, ISSN: 1553-734X
Learning to produce spatiotemporal sequences is a common task that the brain has to solve. The same neural substrate may be used by the brain to produce different sequential behaviours. The way the brain learns and encodes such tasks remains unknown as current computational models do not typically use realistic biologically-plausible learning. Here, we propose a model where a spiking recurrent network of excitatory and inhibitory biophysical neurons drives a read-out layer: the dynamics of the driver recurrent network is trained to encode time which is then mapped through the read-out neurons to encode another dimension, such as space or a phase. Different spatiotemporal patterns can be learned and encoded through the synaptic weights to the read-out neurons that follow common Hebbian learning rules. We demonstrate that the model is able to learn spatiotemporal dynamics on time scales that are behaviourally relevant and we show that the learned sequences are robustly replayed during a regime of spontaneous activity.
Ebner C, Clopath C, Jedlicka P, et al., 2019, Unifying Long-Term Plasticity Rules for Excitatory Synapses by Modeling Dendrites of Cortical Pyramidal Neurons, CELL REPORTS, Vol: 29, Pages: 4295-+, ISSN: 2211-1247
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- Citations: 25
Knopfel T, Sweeney Y, Radulescu CI, et al., 2019, Audio-visual experience strengthens multisensory assemblies in adult mouse visual cortex, Nature Communications, Vol: 10, ISSN: 2041-1723
We experience the world through multiple senses simultaneously. To better understand mechanisms of multisensory processing we ask whether inputs from two senses (auditory and visual) can interact and drive plasticity in neural-circuits of the primary visual cortex (V1). Using genetically-encoded voltage and calcium indicators, we find coincident audio-visual experience modifies both the supra and subthreshold response properties of neurons in L2/3 of mouse V1. Specifically, we find that after audio-visual pairing, a subset of multimodal neurons develops enhanced auditory responses to the paired auditory stimulus. This cross-modal plasticity persists over days and is reflected in the strengthening of small functional networks of L2/3 neurons. We find V1 processes coincident auditory and visual events by strengthening functional associations between feature specific assemblies of multimodal neurons during bouts of sensory driven co-activity, leaving a trace of multisensory experience in the cortical network.
Wilmes KA, Clopath C, 2019, Inhibitory microcircuits for top-down plasticity of sensory representations, Nature Communications, Vol: 10, ISSN: 2041-1723
Rewards influence plasticity of early sensory representations. The underlying changes in cir-cuitry are however unclear. Recent experimental findings suggest that inhibitory circuits regu-late learning. In addition, inhibitory neurons are highly modulated by diverse long-range inputs,including reward signals. We, therefore, hypothesise that inhibitory plasticity plays a major rolein adjusting stimulus representations. We investigate how top-down modulation by rewards in-teracts with local plasticity to induce long-lasting changes in circuitry. Using a computationalmodel of layer 2/3 primary visual cortex, we demonstrate how interneuron circuits can storeinformation about rewarded stimuli to instruct long-term changes in excitatory connectivity inthe absence of further reward. In our model, stimulus-tuned somatostatin-positive interneuronsdevelop strong connections to parvalbumin-positive interneurons during reward such that theyselectively disinhibit the pyramidal layer henceforth. This triggers excitatory plasticity, leadingto increased stimulus representation. We make specific testable predictions and show that thistwo-stage model allows for translation invariance of the learned representation.
Richards BA, Lillicrap TP, Beaudoin P, et al., 2019, A deep learning framework for neuroscience, Nature Neuroscience, Vol: 22, Pages: 1761-1770, ISSN: 1097-6256
Systems neuroscience seeks explanations for how the brain implements a wide variety of perceptual, cognitive and motor tasks. Conversely, artificial intelligence attempts to design computational systems based on the tasks they will have to solve. In the case of artificial neural networks, the three components specified by design are the objective functions, the learning rules, and architectures. With the growing success of deep learning, which utilizes brain-inspired architectures, these three designed components have increasingly become central to how we model, engineer and optimize complex artificial learning systems. Here we argue that a greater focus on these components would also benefit systems neuroscience. We give examples of how this optimization-based framework can drive theoretical and experimental progress in neuroscience. We contend that this principled perspective on systems neuroscience will help to generate more rapid progress.
Udakis M, Pedrosa V, Chamberlain SEL, et al., 2019, Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output
<jats:title>Summary</jats:title><jats:p>The formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.</jats:p>
Nicola W, Clopath C, 2019, A diversity of interneurons and Hebbian plasticity facilitate rapid compressible learning in the hippocampus, Nature Neuroscience, Vol: 22, Pages: 1168-1181, ISSN: 1097-6256
The hippocampus is able to rapidly learn incoming information, even if that information is only observed once. Further, this information can be replayed in a compressed format in either forward or reverse modes during Sharp Wave Ripples (SPW-Rs). We leveraged state-of-the-art techniques in training recurrent spiking networks to demonstrate how primarily interneuron networks can: 1) generate internal theta sequences to bind externally elicited spikes in the presence of inhibition from Medial Septum, 2) compress learned spike sequences in the form of a SPW-R when septal inhibition is removed, 3) generate and refine high-frequency assemblies during SPW-R mediated compression, and 4) regulate the inter-SPW-interval timing between SPW-Rs in ripple clusters. From the fast timescale of neurons to the slow timescale of behaviours, interneuron networks serve as the scaffolding for one-shot learning by replaying, reversing, refining, and regulating spike sequences.
Bono J, Clopath C, 2019, Synaptic plasticity onto inhibitory neurons as a mechanism for ocular dominance plasticity, PLOS COMPUTATIONAL BIOLOGY, Vol: 15
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- Citations: 7
Bouvierm G, Aljadeff J, Clopath C, et 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.
Nicola W, Hellyer PJ, Campbell SA, et 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
Zannone S, Brzosko Z, Paulsen O, et 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.
Sollini J, Chapuis GA, Clopath C, et 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.
González Rueda A, Pedrosa V, Feord R, et 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.
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.
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.
Kaplanis C, Shanahan M, Clopath C, 2018, Continual Reinforcement Learning with Complex Synapses, 35th International Conference on Machine Learning (ICML), Publisher: JMLR-JOURNAL MACHINE LEARNING RESEARCH, ISSN: 2640-3498
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- Citations: 14
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