Presynaptic stochasticity improves energy efficiency and helps alleviate the stabilityplasticity dilemma
Abstract
When an action potential arrives at a synapse there is a large probability that no neurotransmitter is released. Surprisingly, simple computational models suggest that these synaptic failures enable information processing at lower metabolic costs. However, these models only consider information transmission at single synapses ignoring the remainder of the neural network as well as its overall computational goal. Here, we investigate how synaptic failures affect the energy efficiency of models of entire neural networks that solve a goaldriven task. We find that presynaptic stochasticity and plasticity improve energy efficiency and show that the network allocates most energy to a sparse subset of important synapses. We demonstrate that stabilising these synapses helps to alleviate the stabilityplasticity dilemma, thus connecting a presynaptic notion of importance to a computational role in lifelong learning. Overall, our findings present a set of hypotheses for how presynaptic plasticity and stochasticity contribute to sparsity, energy efficiency and improved tradeoffs in the stabilityplasticity dilemma.
Introduction
It has long been known that synaptic signal transmission is stochastic (del Castillo and Katz, 1954). When an action potential arrives at the presynapse, there is a high probability that no neurotransmitter is released – a phenomenon observed across species and brain regions (Branco and Staras, 2009). From a computational perspective, synaptic stochasticity seems to place unnecessary burdens on information processing. Large amounts of noise hinder reliable and efficient computation (Shannon, 1948; Faisal et al., 2005) and synaptic failures appear to contradict the fundamental evolutionary principle of energyefficient processing (Niven and Laughlin, 2008). The brain, and specifically action potential propagation consume a disproportionately large fraction of energy (Attwell and Laughlin, 2001; Harris et al., 2012) – so why propagate action potentials all the way to the synapse only to ignore the incoming signal there?
To answer this neurocomputational enigma various theories have been put forward, see LleraMontero et al., 2019 for a review. One important line of work proposes that individual synapses do not merely maximise information transmission, but rather take into account metabolic costs, maximising the information transmitted per unit of energy (Levy and Baxter, 1996). This approach has proven fruitful to explain synaptic failures (Levy and Baxter, 2002; Harris et al., 2012), low average firing rates (Levy and Baxter, 1996) as well as excitationinhibition balance (Sengupta et al., 2013) and is supported by fascinating experimental evidence suggesting that both presynaptic glutamate release (Savtchenko et al., 2013) and postsynaptic channel properties (Harris et al., 2015; Harris et al., 2019) are tuned to maximise information transmission per energy.
However, so far informationtheoretic approaches have been limited to signal transmission at single synapses, ignoring the context and goals in which the larger network operates. As soon as context and goals guide network computation certain pieces of information become more relevant than others. For instance, when reading a news article the textual information is more important than the colourful ad blinking next to it – even when the latter contains more information in a purely informationtheoretic sense.
Here, we study presynaptic stochasticity on the network level rather than on the level of single synapses. We investigate its effect on (1) energy efficiency and (2) the stabilityplasticity dilemma in model neural networks that learn to selectively extract information from complex inputs.
We find that presynaptic stochasticity in combination with presynaptic plasticity allows networks to extract information at lower metabolic cost by sparsely allocating energy to synapses that are important for processing the given stimulus. As a result, presynaptic release probabilities encode synaptic importance. We show that this notion of importance is related to the Fisher information, a theoretical measure for the network’s sensitivity to synaptic changes.
Building on this finding and previous work (Kirkpatrick et al., 2017), we explore a potential role of presynaptic stochasticity in the stabilityplasticity dilemma. In line with experimental evidence (Yang et al., 2009; HayashiTakagi et al., 2015), we demonstrate that selectively stabilising important synapses improves lifelong learning. Furthermore, these experiments link presynaptically induced sparsity to improved memory.
Model
Our goal is to understand how information processing and energy consumption are affected by stochasticity in synaptic signal transmission. While there are various sources of stochasticity in synapses, here, we focus on modelling synaptic failures where action potentials at the presynapse fail to trigger any postsynaptic depolarisation. The probability of such failures is substantial (Branco and Staras, 2009; Hardingham et al., 2010; Sakamoto et al., 2018) and, arguably, due to its allornothingcharacteristic has the largest effect on both energy consumption and information transmission.
As a growing body of literature suggests, artificial neural networks (ANNs) match several aspects of biological neuronal networks in various goaldriven situations (Kriegeskorte, 2015; Yamins and DiCarlo, 2016; Kell et al., 2018; Banino et al., 2018; Cueva and Wei, 2018; Mattar and Daw, 2018). Crucially, they are the only known model to solve complex vision and reinforcement learning tasks comparably well as humans. We therefore choose to extend this class of models by explicitly incorporating synaptic failures and study their properties in a number of complex visual tasks.
Model details
The basic building blocks of ANNs are neurons that combine their inputs ${a}_{1},\mathrm{\dots},{a}_{n}$ through a weighted sum ${w}_{1}{a}_{1}+\mathrm{\dots}{w}_{n}{a}_{n}$ and apply a nonlinear activation function $\sigma (\cdot )$. The weights $w}_{i$ naturally correspond to synaptic strengths between presynaptic neuron $i$ and the postsynaptic neuron. Although synaptic transmission is classically described as a binomial process (del Castillo and Katz, 1954) most previous modelling studies assume the synaptic strengths to be deterministic. This neglects a key characteristic of synaptic transmission: the possibility of synaptic failures where no communication between pre and postsynapse occurs at all.
In the present study, we explicitly model presynaptic stochasticity by introducing a random variable ${r}_{i}\sim \mathrm{B}\mathrm{e}\mathrm{r}\mathrm{n}\mathrm{o}\mathrm{u}\mathrm{l}\mathrm{l}\mathrm{i}({p}_{i})$, whose outcome corresponds to whether or not neurotransmitter is released. Formally, each synapse $w}_{i$ is activated stochastically according to
so that it has expected synaptic strength ${\overline{w}}_{i}={p}_{i}{m}_{i}$. The postsynaptic neuron calculates a stochastic weighted sum of its inputs with a nonlinear activation
During learning, synapses are updated and both synaptic strength and release probability are changed. We resort to standard learning rules to change the expected synaptic strength. For the multilayer perceptron, this update is based on stochastic gradient descent with respect to a loss function $L(\overline{w},p)$, which in our case is the standard crossentropy loss. Concretely, we have
where the superscript corresponds to time steps. Note that this update is applied to the expected synaptic strength $\overline{{w}_{i}}$, requiring communication between pre and postsynape, see also Discussion. For the explicit update rule of the synaptic strength $m}_{i$ see Materials and methods, Equation (8). For the standard perceptron model, $g}_{i$ is given by its standard learning rule (Rosenblatt, 1958). Based on the intuition that synapses which receive larger updates are more important for solving a given task, we update $p}_{i$ using the update direction $g}_{i$ according to the following simple scheme
Here, ${p}_{\text{up}},{p}_{\text{down}},{g}_{\text{lim}}$ are three metaplasticity parameters shared between all synapses. (We point out that in a noisy learning setting the gradient $g$ does not decay to, so that the learning rule in (4) will maintain network function by keeping certain release probabilities high. See also Materials and methods for a theoretical analysis.) To prevent overfitting and to test robustness, we tune them using one learning scenario and keep them fixed for all other scenarios, see Materials and methods. To avoid inactivated synapses with release probability ${p}_{i}=0$, we clamp $p}_{i$ to stay above 0.25, which we also use as the initial value of $p}_{i$ before learning.
On top of the above intuitive motivation, we give a theoretical justification for this learning rule in Materials and methods, showing that synapses with larger Fisher information obtain high release probabilities, also see Figure 2d.
Box 1.
Mutual Information.
The Mutual Information $I(Y;Z)$ of two jointly distributed random variables $Y,Z$ is a common measure of their dependence (Shannon, 1948). Intuitively, mutual information captures how much information about $Y$ can be obtained from $Z$, or vice versa. Formally, it is defined as
Where $H(Y)$ is the entropy of $Y$ and $H(YZ)$ is the conditional entropy of $Y$ given $Z$. In our case, we want to measure how much taskrelevant information $Y$ is contained in the neural network output $Z$. For example, the neural network might receive as input a picture of a digit with the goal of predicting the identity of the digit. Both the groundtruth digit identity $Y$ and the network’s prediction $Z$ are random variables depending on the random image $X$. The measure $I(Y;Z)$ quantifies how much of the behaviourally relevant information $Y$ is contained in the network’s prediction $Z$ ignoring irrelevant information also present in the complex, highentropy image $X$.
Measuring energy consumption
For our experiments, we would like to quantify the energy consumption of the neural network. Harris et al., 2012 find that the main constituent of neural energy demand is synaptic signal transmission and that the cost of synaptic signal transmission is dominated by the energy needed to reverse postsynaptic ion fluxes. In our model, the component most closely matching the size of the postsynaptic current is the expected synaptic strength, which we therefore take as measure for the model’s energy consumption. In the Appendix, we also measure the metabolic cost incurred by the activity of neurons by calculating their average rate of activity.
Measuring information transmission
We would like to measure how well the neural network transmits information relevant to its behavioural goal. In particular, we are interested in the setting where the complexity of the stimulus is high relative to the amount of information that is relevant for the behavioural goal. To this end, we present complex visual inputs with high information content to the network and teach it to recognise the object present in the image. We then measure the mutual information between network output and object identity, see Box 1.
Results
Presynaptic stochasticity enables energyefficient information processing
We now investigate the energy efficiency of a network that learns to classify digits from the MNIST handwritten digit dataset (LeCun, 1998). The inputs are highdimensional with high entropy, but the relevant information is simply the identity of the digit. We compare the model with plastic, stochastic release to two controls. A standard ANN with deterministic synapses is included to investigate the combined effect of presynaptic stochasticity and plasticity. In addition, to isolate the effect of presynaptic plasticity, we introduce a control which has stochastic release, but with a fixed probability. In this control, the release probability is identical across synapses and chosen to match the average release probability of the model with plastic release after it has learned the task.
All models are encouraged to find lowenergy solutions by penalising large synaptic weights through standard ${\mathrm{\ell}}_{2}$regularisation. Figure 1a shows that different magnitudes of ${\mathrm{\ell}}_{2}$regularisation induce different informationenergy tradeoffs for all models, and that the model with plastic, stochastic release finds considerably more energyefficient solutions than both controls, while the model with nonplastic release requires more energy then the deterministic model. Together, this supports the view that a combination of presynaptic stochasticity and plasticity promotes energyefficient information extraction.
In addition, we investigate how stochastic release helps the network to lower metabolic costs. Intuitively, a natural way to save energy is to assign high release probabilities to synapses that are important to extract relevant information and to keep remaining synapses at a low release probability. Figure 2a shows that after learning, there are indeed few synapses with high release probabilities, while most release probabilities are kept low. We confirm that this sparsity develops independently of the initial value of release probabilities before learning, see Appendix 1—figure 1d. To test whether the synapses with high release probabilities are most relevant for solving the task we perform a lesion experiment. We successively remove synapses with low release probability and measure how well the lesioned network still solves the given task, see Figure 2b. As a control, we remove synapses in a random order independent of their release probability. We find that maintaining synapses with high release probabilities is significantly more important to network function than maintaining random ones. Moreover, we find, as expected, that synapses with high release probabilities consume considerably more energy than synapses with low release probability, see Figure 2c. This supports the hypothesis that the model identifies important synapses for the task at hand and spends more energy on these synapses while saving energy on irrelevant ones.
We have seen that the network relies on a sparse subset of synapses to solve the task efficiently. However, sparsity is usually thought of on a neuronal level, with few neurons rather than few synapses encoding a given stimulus. Therefore, we quantify sparsity of our model on a neuronal level. For each neuron, we count the number of ‘important’ input and output synapses, where we define ‘important’ to correspond to a release probability of at least $p=0.9$. Note that the findings are robust with respect to the precise value of $p$, see Figure 2a. We find that the distribution of important synapses per neuron is inhomogeneous and significantly different from a randomly shuffled baseline with a uniform distribution of active synapses (KolmogorovSmirnoff test, $D=0.505,p<0.01$), see Figure 3a. Thus, some neurons have disproportionately many important inputs, while others have very few, suggesting sparsity on a neuronal level. As additional quantification of this effect, we count the number of highly important neurons, where we define a neuron to be highly important if its number of active inputs is two standard deviations below or above the mean (mean and standard deviation from shuffled baseline). We find that our model network with presynaptic stochasticity has disproportionate numbers of highly important and unimportant neurons, see Figure 3b. Moreover, we check whether neurons with many important inputs tend to have many important outputs, indeed finding a correlation of $r=0.93$, see Figure 3c. These analyses all support the claim that the network is sparse not only on a synaptic but also on a neuronal level.
Finally, we investigate how release probabilities evolve from a theoretical viewpoint under the proposed learning rule. Note that the evolution of release probabilities is a random process, since it depends on the random input to the network. Under mild assumptions, we show (Materials and methods) that release probabilities are more likely to increase for synapses with large Fisher information (In this context, the Fisher information is a measure of sensitivity of the network to changes in synapses, measuring how important preserving a given synapse is for network function.). Thus, synapses with large release probabilities will tend to have high Fisher information. We validate this theoretical prediction empirically, see Figure 2d.
Presynaptically driven consolidation helps alleviate the stabilityplasticity dilemma
While the biological mechanisms addressing the stabilityplasticity dilemma are diverse and not fully understood, it has been demonstrated experimentally that preserving memories requires maintaining the synapses which encode these memories (Yang et al., 2009; HayashiTakagi et al., 2015; Cichon and Gan, 2015). In this context, theoretical work suggests that the Fisher information is a useful way to quantify which synapses should be maintained (Kirkpatrick et al., 2017). Inspired by these insights, we hypothesise that the synaptic importance encoded in release probabilities can be used to improve the network’s memory retention by selectively stabilising important synapses.
We formalise this hypothesis in our model by lowering the learning rate (plasticity) of synapses according to their importance (release probability). Concretely, the learning rate $\eta =\eta ({p}_{i})$ used in (3) is scaled as follows
such that the learning rate is smallest for important synapses with high release probability. ${\eta}_{0}$ denotes a base learning rate that is shared by all synapses. We complement this consolidation mechanism by freezing the presynaptic release probabilities $p}_{i$ once they have surpassed a predefined threshold ${p}_{\text{freeze}}$. This ensures that a synapse whose presynaptic release probability was high for a previous task retains its release probability even when unused during consecutive tasks. In other words, the effects of presynaptic longterm depression (LTD) are assumed to act on a slower timescale than learning single tasks. Note that the freezing mechanism ensures that all synaptic strengths ${\overline{w}}_{i}$ retain a small degree of plasticity, since the learning rate modulation factor $(1{p}_{i})$ remains greater than 0.
To test our hypothesis that presynaptically driven consolidation allows the network to make improved stabilityplasticity tradeoffs, we sequentially present a number of tasks and investigate the networks behaviour. We mainly focus our analysis on a variation of the MNIST handwritten digit dataset, in which the network has to successively learn the parity of pairs of digits, see Figure 4a. Additional experiments are reported in the Appendix, see Appendix 1—table 1.
First, we investigate whether presynaptic consolidation improves the model’s ability to remember old tasks. To this end, we track the accuracy on the first task over the course of learning, see Figure 4b. As a control, we include a model without consolidation and with deterministic synapses. While both models learn the first task, the model without consolidation forgets more quickly, suggesting that the presynaptic consolidation mechanism does indeed improve memory.
Next, we ask how increased stability interacts with the network’s ability to remain plastic and learn new tasks. To assess the overall tradeoff between stability and plasticity, we report the average accuracy over all five tasks, see Figure 4c.
We find that the presynaptic consolidation model performs better than a standard model with deterministic synapses and without consolidation. In addition, we compare performance to two stateofthe art machine learning algorithms: The wellknown algorithm Elastic Weight Consolidation (EWC) (Kirkpatrick et al., 2017) explicitly relies on the Fisher information and performs a separate consolidation phase after each task. Bayesian Gradient Descent (BGD) (Zeno et al., 2018) is a Bayesian approach that models synapses as distributions, but does not capture the discrete nature of synaptic transmission. The presynaptic consolidation mechanism performs better than both these stateoftheart machine learning algorithms, see Figure 4c. Additional experiments in the Appendix suggest overall similar performance of Presynaptic Consolidation to BGD and similar or better performance than EWC.
To determine which components of our model contribute to its lifelong learning capabilities, we perform an ablation study, see Figure 5a. We aim to separate the effect of (1) consolidation mechanisms and (2) presynaptic plasticity.
First, we remove the two consolidation mechanisms, learning rate modulation and freezing release probabilities, from the model with stochastic synapses. This yields a noticeable decrease in performance during lifelong learning, thus supporting the view that stabilising important synapses contributes to addressing the stabilityplasticity dilemma.
Second, we aim to disentangle the effect of presynaptic plasticity from the consolidation mechanisms. We therefore introduce a control in which presynaptic plasticity but not consolidation is blocked. Concretely, the control has ‘ghost release probabilities’ ${\stackrel{~}{p}}_{i}$ evolving according to Equation (4) and modulating plasticity according to Equation (5); but the synaptic release probability is fixed at 0.5. We see that this control performs worse than the original model with a drop in accuracy of 1.4 on Split MNIST ($t=3.44$, $p<0.05$) and a drop of accuracy of 5.6 on Permuted MNIST ($t=6.72,p<0.01$). This suggests that presynaptic plasticity, on top of consolidation, helps to stabilise the network. We believe that this can be attributed to the sparsity induced by the presynaptic plasticity which decreases overlap between different tasks.
The above experiments rely on a gradientbased learning rule for multilayer perceptrons. To test whether presynaptic consolidation can also alleviate stabilityplasticity tradeoffs in other settings, we study its effects on learning in a standard perceptron (Rosenblatt, 1958). We train the perceptron sequentially on five pattern memorisation tasks, see Materials and methods for full details. We find that the presynaptically consolidated perceptron maintains a more stable memory of the first task, see Figure 5b. In addition, this leads to an overall improved stabilityplasticity tradeoff, see Figure 5c and shows that the effects of presynaptic consolidation in our model extend beyond gradientbased learning.
Discussion
Main contribution
Information transmission in synapses is stochastic. While previous work has suggested that stochasticity allows to maximise the amount of information transmitted per unit of energy spent, this analysis has been restricted to single synapses. We argue that the relevant quantity to be considered is taskdependent information transmitted by entire networks. Introducing a simple model of the allornothing nature of synaptic transmission, we show that presynaptic stochasticity enables networks to allocate energy more efficiently. We find theoretically as well as empirically that learned release probabilities encode the importance of weights for network function according to the Fisher information. Based on this finding, we suggest a novel computational role for presynaptic stochasticity in lifelong learning. Our experiments provide evidence that coupling information encoded in the release probabilities with modulated plasticity can help alleviate the stabilityplasticity dilemma.
Modelling assumptions and biological plausibility
Stochastic synaptic transmission
Our model captures the occurrence of synaptic failures by introducing a Bernoulli random variable governing whether or not neurotransmitter is released. Compared to classical models assuming deterministic transmission, this is one step closer to experimentally observed binomial transmission patterns, which are caused by multiple, rather than one, release sites between a given neuron and dendritic branch. Importantly, our simplified model accounts for the event that there is no postsynaptic depolarisation at all. Even in the presence of multiple release sites, this event has nonnegligible probability: Data from cultured hippocampal neurons (Branco et al., 2008, Figure 2D) and the neocortex (Hardingham et al., 2010, Appendix 1—figure 2c) shows that the probability ${(1p)}^{N}$ that none of $N$ release sites with release probability $p$ is active, is around 0.3–0.4 even for $N$ as large as 10. More recent evidence suggests an even wider range of values depending on the extracellular calcium concentration (Sakamoto et al., 2018).
Presynaptic longterm plasticity
A central property of our model builds on the observation that the locus of expression for longterm plasticity can both be presynaptic and postsynaptic (Larkman et al., 1992; Lisman and Raghavachari, 2006; Bayazitov et al., 2007; Sjöström et al., 2007; Bliss and Collingridge, 2013; Costa et al., 2017). The mechanisms to change either are distinct and synapsespecific (Yang and Calakos, 2013; Castillo, 2012), but how exactly pre and postsynaptic forms of longterm potentiation (LTP) and longterm depression (LTD) interact is not yet fully understood (Monday et al., 2018). The induction of longterm plasticity is thought to be triggered postsynaptically for both presynaptic and postsynaptic changes (Yang and Calakos, 2013; Padamsey and Emptage, 2014) and several forms of presynaptic plasticity are known to require retrograde signalling (Monday et al., 2018), for example through nitric oxide or endocannabinoids (Heifets and Castillo, 2009; AndradeTalavera et al., 2016; Costa et al., 2017). This interaction between pre and postsynaptic sites is reflected by our learning rule, in which both pre and postsynaptic changes are governed by postsynaptic updates and require communication between pre and postsynapse. The proposed presynaptic updates rely on both presynaptic LTP and presynaptic LTD. At least one form of presynaptic longterm plasticity is known to be bidirectional switching from potentiation to depression depending on endocannabinoid transients (Cui et al., 2015; Cui et al., 2016).
Link between presynaptic release and synaptic stability
Our model suggests that increasing the stability of synapses with large release probability improves memory. Qualitatively, this is in line with observations that presynaptic boutons, which contain stationary mitochondria (Chang et al., 2006; Obashi and Okabe, 2013), are more stable than those which do not, both on short (Sun et al., 2013) and long timescales of at least weeks (Lees et al., 2019). Quantitatively, we find evidence for such a link by reanalysing data (Data was made publicly available in Costa et al., 2017). from Sjöström et al., 2001 for a spiketimingdependent plasticity protocol in the rat primary visual cortex: Appendix 1—figure 4 shows that synapses with higher initial release probability are more stable than those with low release probabilities for both LTP and LTD.
Credit assignment
In our multilayer perceptron model, updates are computed using backpropagated gradients. Whether credit assignment in the brain relies on backpropagation – or more generally gradients – remains an active area of research, but several alternatives aiming to increase biological plausibility exist and are compatible with our model (Sacramento et al., 2018; Lillicrap et al., 2016; Lee et al., 2015). To check that the proposed mechanism can also operate without gradient information, we include an experiment with a standard perceptron and its gradientfree learning rule (Rosenblatt, 1958), see Figure 5b, c.
Correspondence to biological networks
We study general ratebased neural networks raising the question in which biological networks or contexts one might expect the proposed mechanisms to be at work. Our experiments suggest that improved energy efficiency can at least partly be attributed to the sparsification induced by presynaptic stochasticity (cf. Olshausen and Field, 2004). Networks which are known to rely on sparse representations are thus natural candidates for the dynamics investigated here. This includes a wide range of sensory networks (PerezOrive et al., 2002; Hahnloser et al., 2002; Crochet et al., 2011; Quiroga et al., 2005) as well as areas in the hippocampus (Wixted et al., 2014; Lodge and Bischofberger, 2019).
In the context of lifelong learning, our learning rule provides a potential mechanism that helps to slowly incorporate new knowledge into a network with preexisting memories. Generally, the introduced consolidation mechanism could benefit the slow part of a complementary learning system as proposed by McClelland et al., 1995; Kumaran et al., 2016. Sensory networks in particular might utilize such a mechanism as they require to learn new stimuli while retaining the ability to recognise previous ones (Buonomano and Merzenich, 1998; Gilbert et al., 2009; Moczulska et al., 2013). Indeed, in line with the hypothesis that synapses with larger release probability are more stable, it has been observed that larger spines in the mouse barrel cortex are more stable. Moreover, novel experiences lead to the formation of new, stable spines, similar to our findings reported in Appendix 1—figure 3b.
Related synapse models
Probabilistic synapse models
The goal of incorporating and interpreting noise in models of neural computation is shared by many computational studies. Inspired by a Bayesian perspective, neural variability is often interpreted as representing uncertainty (Ma et al., 2006; Fiser et al., 2010; Kappel et al., 2015; Haefner et al., 2016), or as a means to prevent overfitting (Wan et al., 2013). The Bayesian paradigm has been applied directly to variability of individual synapses in neuroscience (Aitchison et al., 2014; Aitchison and Latham, 2015; Aitchison et al., 2021) and machine learning (Zeno et al., 2018). It prescribes decreasing the plasticity of synapses with low posterior variance. A similiar relationship can be shown to hold for our model as described in the Material and Methods. In contrast to common Bayesian interpretations (Zeno et al., 2018; Aitchison and Latham, 2015; Kappel et al., 2015) which model release statistics as Gaussians and optimise complex objectives (see also LleraMontero et al., 2019) our simple proposal represents the inherently discrete nature of synaptic transmission more faithfully.
Complex synapse models
In the context of lifelong learning, our model’s consolidation mechanism is similar to Elastic Weight Consolidation (EWC) (Kirkpatrick et al., 2017), which explicitly relies on the Fisher information to consolidate synapses. Unlike EWC, our learning rule does not require a task switch signal and does not need a separate consolidation phase. Moreover, our model can be interpreted as using distinct states of plasticity to protect memories. This general idea is formalised and analysed thoroughly by theoretical work on cascade models of plasticity (Fusi et al., 2005; Roxin and Fusi, 2013; Benna and Fusi, 2016). The resulting model (Benna and Fusi, 2016) has also been shown to be effective in lifelong learning settings (Kaplanis et al., 2018).
Synaptic importance may govern energyinformation tradeoffs
Energy constraints are widely believed to be a main driver of evolution (Niven and Laughlin, 2008). From brain size (Isler and van Schaik, 2009; Navarrete et al., 2011), to wiring cost (Chen et al., 2006), down to ion channel properties (Alle et al., 2009; Sengupta et al., 2010), presynaptic transmitter release (Savtchenko et al., 2013) and postsynaptic conductance (Harris et al., 2015), various components of the nervous system have been shown to be optimal in terms of their total metabolic cost or their metabolic cost per bit of information transmitted.
Crucially, there is evidence that the central nervous system operates in varying regimes, making different tradeoffs between synaptic energy demand and information transmission: Perge et al., 2009; Carter and Bean, 2009; Hu and Jonas, 2014 all find properties of the axon (thickness, sodium channel properties), which are suboptimal in terms of energy per bit of information. They suggest that these inefficiencies occur to ensure fast transmission of highly relevant information.
We propose that a similar energy/information tradeoff could govern network dynamics preferentially allocating more energy to the most relevant synapses for a given task. Our model relies on a simple, theoretically justified learning rule to achieve this goal and leads to overall energy savings. Neither the tradeoff nor the overall savings can be accounted for by previous frameworks for energyefficient information transmission at synapses (Levy and Baxter, 2002; Harris et al., 2012).
This view of release probabilities and related metabolic cost provides a way to make the informal notion of ‘synaptic importance’ concrete by measuring how much energy is spent on a synapse. Interestingly, our model suggests that this notion is helpful beyond purely energetic considerations and can in fact help to maintain memories during lifelong learning.
Materials and methods
Summary of learning rule
Request a detailed protocolOur learning rule has two components, an update for the presynaptic release probability $p}_{i$ and an update for the postsynaptic strength $m}_{i$. The update of the synaptic strength $m}_{i$ is defined implicitly through updating the expected synaptic strength $\overline{w}$
and the presynaptic update is given by
This leads to the following explicit update rule for the synaptic strength ${m}_{i}=\frac{{\overline{w}}_{i}}{{p}_{i}}$
where we used the chain rule to rewrite ${g}_{i}=\frac{\partial L}{\partial \overline{{w}_{i}}}=\frac{\partial L}{\partial {m}_{i}}\cdot \frac{\partial {m}_{i}}{\partial \overline{{w}_{i}}}=\frac{\partial L}{\partial {m}_{i}}\cdot \frac{1}{{p}_{i}}$. For the lifelong learning experiment, we additionally stabilise high release probability synapses by multiplying the learning rate by $(1{p}_{i})$ for each synapse and by freezing release probabilities (but not strengths) when they surpass a predefined threshold ${p}_{\text{freeze}}$.
Theoretical analysis of presynaptic learning rule
As indicated in the results section the release probability $p}_{i$ is more likely to be large when the Fisher information of the synaptic strength $w}_{i$ is large as well. This provides a theoretical explanation to the intuitive correspondence between release probability and synaptic importance. Here, we formalise this link starting with a brief review of the Fisher information.
Fisher information
Request a detailed protocolThe Fisher information is a measure for the networks sensitivity to changes in parameters. Under additional assumptions it is equal to the Hessian of the loss function (Pascanu and Bengio, 2013; Martens, 2014), giving an intuitive reason why synapses with high Fisher information should not be changed much if network function is to be preserved.
Formally, for a model with parameter vector $\theta $ predicting a probability distribution ${f}_{\theta}(X,y)$ for inputs $X$ and labels $y$ drawn from a joint distribution $\mathcal{D}$, the Fisher information matrix is defined as
Note that this expression is independent of the actual labels $y$ of the dataset and that instead we sample labels from the model’s predictions. If the model makes correct predictions, we can replace the second expectation, which is over $y\sim {f}_{\theta}(y\mid X)$, by the empirical labels $y$ of the dataset for an approximation called the Empirical Fisher information. If we further only consider the diagonal entries – corresponding to a meanfield approximation – and write ${g}_{i}(X,y)=\frac{\partial \mathrm{ln}{f}_{\theta}(X,y)}{\partial {\theta}_{i}}$ we obtain the following expression for the $i$th entry of the diagonal Empirical Fisher information:
Note that this version of the Fisher information relies on the same gradients that are used to update the parameters of the multilayer perceptron, see Equations (3), (4).
Under the assumption that the learned probability distribution $f(\cdot \mid X,\theta )$ equals the real probability distribution, the Fisher information equals the Hessian of the cross entropy loss (i.e. the negative logprobabilities) with respect to the model parameters (Pascanu and Bengio, 2013; Martens, 2014). The Fisher information was previously used in machine learning to enable lifelong learning (Kirkpatrick et al., 2017; Huszár, 2018) and it has been shown that other popular lifelong learning methods implicitly rely on the Fisher information (Benzing, 2020).
Link between release probabilities and Fisher information
Request a detailed protocolWe now explain how our learning rule for the release probability is related to the Fisher information. For simplicity of exposition, we focus our analysis on a particular sampled subnetwork with deterministic synaptic strengths. Recall that update rule (4) for release probabilities increases the release probability, if the gradient magnitude ${g}_{i}$ is above a certain threshold, ${g}_{i}>{g}_{\text{lim}}$, and decreases them otherwise. Let us denote by ${p}_{i}^{+}$ the probability that the $i$th release probability is increased. Then
where the probability space corresponds to sampling training examples. Note that $\mathbb{E}[{g}_{i}^{2}]={F}_{i}$ by definition of the Empirical Fisher information ${F}_{i}$. So if we assume that $\mathrm{Pr}[{g}_{i}^{2}>{g}_{\text{lim}}^{2}]$ depends monotonically on $\mathbb{E}[{g}_{i}^{2}]$ then we already see that ${p}_{i}^{+}$ depends monotonically on ${F}_{i}$. This in turn implies that synapses with a larger Fisher information are more likely to have a large release probability, which is what we claimed. We now discuss the assumption made above.
Assumption: $Pr[{g}_{i}^{2}>{g}_{\text{lim}}^{2}]$ depends monotonically on $\mathbb{E}[{g}_{i}^{2}]$
Request a detailed protocolWhile this assumption is not true for arbitrary distributions of $g$, it holds for many commonly studied parametric families and seems likely to hold (approximately) for realistic, nonadversarially chosen distributions. For example, if each $g}_{i$ follows a normal distribution ${g}_{i}\sim \mathcal{N}({\mu}_{i},{\sigma}_{i}^{2})$ with varying ${\sigma}_{i}$ and ${\sigma}_{i}\gg {\mu}_{i}$, then
and
so that ${p}_{i}^{+}$ is indeed monotonically increasing in ${F}_{i}$. Similar arguments can be made for example for a Laplace distribution, with scale larger than mean.
Link between learning rate modulation and Bayesian updating
Request a detailed protocolRecall that we multiply the learning rate of each synapse by $(1{p}_{i})$, see Equation (5). This learning rate modulation can be related to the update prescribed by Bayesian modelling. As shown before, synapses with large Fisher information tend to have large release probability, which results in a decrease of the plasticity of synapses with large Fisher information. We can treat the (diagonal) Fisher information as an approximation of the posterior precision based on a Laplace approximation of the posterior likelihood (Kirkpatrick et al., 2017) which exploits that the Fisher information approaches the Hessian of the loss as the task gets learned (Martens, 2014). Using this relationship, our learning rate modulation tends to lower the learning rate of synapses with low posterior variance as prescribed by Bayesian modelling.
Practical approximation
Request a detailed protocolThe derivation above assumes that each gradient $g$ is computed using a single input, so that $\mathbb{E}[{g}^{2}]$ equals the Fisher information. While this may be the biologically more plausible setting, in standard artificial neural network (ANN) training the gradient is averaged across several inputs (minibatches). Despite this modification, ${g}^{2}$ remains a good, and commonly used, approximation of the Fisher, see for example Khan et al., 2018; Benzing, 2020.
Perceptron for lifelong learning
To demonstrate that our findings on presynaptic stochasticity and plasticity are applicable to other models and learning rules, we include experiments for the standard perceptron (Rosenblatt, 1958) in a lifelong learning setting.
Model
Request a detailed protocolThe perceptron is a classical model for a neuron with multiple inputs and threshold activation function. It is used to memorise the binary labels of a number of input patterns where input patterns are sampled uniformly from ${\{1,1\}}^{N}$ and their labels are sampled uniformly from $\{1,1\}$. Like in ANNs, the output neuron of a perceptron computes a weighted sum of its inputs followed by nonlinear activation $\sigma (\cdot )$:
The only difference to the ANN model is that the nonlinearity is the sign function and that there is only one layer. We model each synapse $w}_{i$ as a Bernoulli variable $r}_{i$ with synaptic strength $m}_{i$ and release probability $p}_{i$ just as before, see Equation (1). The expected strengths ${\overline{w}}_{i}$ are learned according to the standard perceptron learning rule (Rosenblatt, 1958). The only modification we make is averaging weight updates across 5 inputs, rather than applying an update after each input. Without this modification, the update size $g}_{i$ for each weight $w}_{i$ would be constant according to the perceptron learning rule. Consequently, our update rule for $p}_{i$ would not be applicable. However, after averaging across five patterns we can apply the same update rule for $p}_{i$ as previously, see Equation (4), and also use the same learning rate modification, see Equation (5). We clarify that $g}_{i$ now refers to the update of expected strength ${\overline{w}}_{i}$. In the case of ANN this is proportional to the gradient, while in the case of the nondifferentiable perceptron it has no additional interpretation.
Experiments
Request a detailed protocolFor the lifelong learning experiments, we used five tasks, each consisting of 100 randomly sampled and labelled patterns of size $N=1000$. We compared the perceptron with learned stochastic weights to a standard perceptron. For the standard perceptron, we also averaged updates across five patterns. Both models were sequentially trained on five tasks, using 25 passes through the data for each task.
We note that for more patterns, when the perceptron gets closer to its maximum capacity of $2N$, the average accuracies of the stochastic and standard perceptron become more similar, suggesting that the benefits of stochastic synapses occur when model capacity is not fully used.
As metaplasticity parameters we used ${g}_{\text{lim}}=0.1,{p}_{\text{up}}={p}_{\text{down}}=0.2$ and ${p}_{\text{min}}=0.25,{p}_{\text{freeze}}=0.9$. These were coarsely tuned on an analogous experiment with only two tasks instead of five.
Experimental setup
Code availability
Request a detailed protocolCode for all experiments is publicly available at github.com/smonsays/presynapticstochasticity (Schug, 2021, copy archived at swh:1:rev:de0851773cd1375b885dcdb18e711a2fb6eb06a4).
Metaplasticity parameters
Request a detailed protocolOur method has a number of metaplasticity parameters, namely ${p}_{\text{up}}$, ${p}_{\text{down}}$, ${g}_{\text{lim}}$ and the learning rate $\eta $. For the lifelong learning experiments, there is an additional parameter ${p}_{\text{freeze}}$. For the energy experiments, we fix ${p}_{\text{up}}={p}_{\text{down}}=0.07$, ${g}_{\text{lim}}=0.001$ and choose $\eta =0.05$ based on coarse, manual tuning. For the lifelong learning experiments, we choose ${\eta}_{0}\in \{0.01,0.001\}$ and optimise the remaining metaplasticity parameters through a random search on one task, namely Permuted MNIST, resulting in ${p}_{\text{up}}=0.0516$, ${p}_{\text{down}}=0.0520$ and ${g}_{\text{lim}}=0.001$. We use the same fixed parametrisation for all other tasks, namely Permuted Fashion MNIST, Split MNIST and Split Fashion MNIST (see below for detailed task descriptions). For the ablation experiment in Figure 5a, metaplasticity parameters were reoptimised for each ablation in a random search to ensure a fair, meaningful comparison.
Model robustness
Request a detailed protocolWe confirmed that the model is robust with respect to the exact choice of parameters. For the energy experiments, de or increasing ${p}_{\text{up}},{p}_{\text{down}}$ by 25 does not qualitatively change results.
For the lifelong learning experiment, the chosen tuning method is a strong indicator of robustness: The metaplasticitiy parameters are tuned on one setup (Permuted MNIST) and then transferred to others (Split MNIST, Permuted and Split Fashion MNIST). The results presented in Appendix 1—table 1 show that the parameters found in one scenario are robust and carry over to several other settings. We emphasise that the differences between these scenarios are considerable. For example, for permuted MNIST consecutive input distributions are essentially uncorrelated by design, while for Split (Fashion) MNIST input distributions are strongly correlated. In addition, from MNIST to Fashion MNIST the number of ‘informative’ pixels changes drastically.
Lifelong learning tasks
Request a detailed protocolFor the lifelong learning experiments, we tested our method as well as baselines in several scenarios on top of the Split MNIST protocol described in the main text.
Permuted MNIST
Request a detailed protocolIn the Permuted MNIST benchmark, each task consists of a random but fixed permutation of the input pixels of all MNIST images (Goodfellow et al., 2013). We generate 10 tasks using this procedure and present them sequentially without any indication of task boundaries during training. A main reason to consider the Permuted MNIST protocol is that it generates tasks of equal difficulty.
Permuted and split fashion MNIST
Request a detailed protocolBoth the Split and Permuted protocol can be applied to other datasets. We use them on the Fashion MNIST dataset (Xiao et al., 2017) consisting of 60,000 greyscale images of 10 different fashion items with $28\times 28$ pixels.
Continuous permuted MNIST
We carry out an additional experiment on the continuous Permuted MNIST dataset (Zeno et al., 2018). This is a modified version of the Permuted MNIST dataset which introduces a smooth transition period between individual tasks where data from both distributions is mixed. It removes the abrupt change between tasks and allows us to investigate if our method depends on such an implicit task switch signal. We observe a mean accuracy over all tasks of $0.8539\pm 0.006$ comparable to the noncontinuous case suggesting that our method does not require abrupt changes from one task to another.
Neural network training
Request a detailed protocolOur neural network architecture consists of two fully connected hidden layers of 200 neurons without biases with rectified linear unit activation functions $\sigma (x)$. The final layer uses a softmax and crossentropy loss. Network weights were initialised according to the PyTorch default for fully connected layers, which is similar to Kaiming uniform initialisation (Glorot and Bengio, 2010; He et al., 2015) but divides weights by an additional factor of √6. We use standard stochastic gradient descent to update the average weight ${\overline{w}}_{i}$ only altered by the learning rate modulation described for the lifelong learning experiments. We use a batch size of 100 and train each task for 10 epochs in the lifelong learning setting. In the energyinformation experiments we train the model for 50 epochs.
Appendix 1
Data availability
Code for experiments is part of the submission and is published on GitHub (https://github.com/smonsays/presynapticstochasticity copy archived at https://archive.softwareheritage.org/swh:1:rev:de0851773cd1375b885dcdb18e711a2fb6eb06a4).

Dryad Digital RepositoryData from: Unified pre and postsynaptic longterm plasticity enables reliable and flexible learning.https://doi.org/10.5061/dryad.p286g
References

Synaptic plasticity as bayesian inferenceNature Neuroscience 24:565–571.https://doi.org/10.1038/s41593021008095

An energy budget for signaling in the grey matter of the brainJournal of Cerebral Blood Flow & Metabolism 21:1133–1145.https://doi.org/10.1097/0000464720011000000001

Slow presynaptic and fast postsynaptic components of compound longterm potentiationJournal of Neuroscience 27:11510–11521.https://doi.org/10.1523/JNEUROSCI.307707.2007

Computational principles of synaptic memory consolidationNature Neuroscience 19:1697–1706.https://doi.org/10.1038/nn.4401

The probability of neurotransmitter release: variability and feedback control at single synapsesNature Reviews Neuroscience 10:373–383.https://doi.org/10.1038/nrn2634

Cortical plasticity: from synapses to mapsAnnual Review of Neuroscience 21:149–186.https://doi.org/10.1146/annurev.neuro.21.1.149

. (2012). Presynaptic ltp and ltd of excitatory and inhibitory synapsesCold Spring Harbor Perspectives in Biology 4:a005728.https://doi.org/10.1101/cshperspect.a005728

Mitochondrial trafficking to synapses in cultured primary cortical neuronsJournal of Neuroscience 26:7035–7045.https://doi.org/10.1523/JNEUROSCI.101206.2006

Endocannabinoids mediate bidirectional striatal spiketimingdependent plasticityThe Journal of Physiology 593:2833–2849.https://doi.org/10.1113/JP270324

Quantal components of the endplate potentialThe Journal of Physiology 124:560–573.https://doi.org/10.1113/jphysiol.1954.sp005129

Statistically optimal perception and learning: from behavior to neural representationsTrends in Cognitive Sciences 14:119–130.https://doi.org/10.1016/j.tics.2010.01.003

Perceptual learning and adult cortical plasticityThe Journal of Physiology 587:2743–2751.https://doi.org/10.1113/jphysiol.2009.171488

ConferenceUnderstanding the difficulty of training deep feedforward neural networksProceedings of the Thirteenth International Conference on Artificial Intelligence and Statistics. pp. 249–256.

EnergyEfficient information transfer by visual pathway synapsesCurrent Biology 25:3151–3160.https://doi.org/10.1016/j.cub.2015.10.063

Energyefficient information transfer at Thalamocortical synapsesPLOS Computational Biology 15:e1007226.https://doi.org/10.1371/journal.pcbi.1007226

ConferenceDelving Deep Into Rectifiers: Surpassing HumanLevel Performance on Imagenet ClassificationProceedings of the IEEE International Conference on Computer Vision. pp. 1026–1034.

Endocannabinoid signaling and longterm synaptic plasticityAnnual Review of Physiology 71:283–306.https://doi.org/10.1146/annurev.physiol.010908.163149

The expensive brain: a framework for explaining evolutionary changes in brain sizeJournal of Human Evolution 57:392–400.https://doi.org/10.1016/j.jhevol.2009.04.009

ConferenceContinual reinforcement learning with complex synapsesInternational Conference on Machine Learning. pp. 2497–2506.

Network plasticity as bayesian inferencePLOS Computational Biology 11:e1004485.https://doi.org/10.1371/journal.pcbi.1004485

Deep neural networks: a new framework for modeling biological vision and brain information processingAnnual Review of Vision Science 1:417–446.https://doi.org/10.1146/annurevvision082114035447

What learning systems do intelligent agents need? complementary learning systems theory updatedTrends in Cognitive Sciences 20:512–534.https://doi.org/10.1016/j.tics.2016.05.004

ConferenceDifference Target PropagationMachine Learning and Knowledge Discovery in Databases. pp. 498–515.https://doi.org/10.1007/9783319235288_31

Presynaptic boutons that contain mitochondria are more stableFrontiers in Synaptic Neuroscience 11:37.https://doi.org/10.3389/fnsyn.2019.00037

Energy efficient neural codesNeural Computation 8:531–543.https://doi.org/10.1162/neco.1996.8.3.531

Energyefficient neuronal computation via quantal synaptic failuresThe Journal of Neuroscience 22:4746–4755.https://doi.org/10.1523/JNEUROSCI.221104746.2002

Computational roles of plastic probabilistic synapsesCurrent Opinion in Neurobiology 54:90–97.https://doi.org/10.1016/j.conb.2018.09.002

Synaptic properties of newly generated granule cells support sparse coding in the adult hippocampusBehavioural Brain Research 372:112036.https://doi.org/10.1016/j.bbr.2019.112036

Bayesian inference with probabilistic population codesNature Neuroscience 9:1432–1438.https://doi.org/10.1038/nn1790

Prioritized memory access explains planning and hippocampal replayNature Neuroscience 21:1609–1617.https://doi.org/10.1038/s415930180232z

Energy limitation as a selective pressure on the evolution of sensory systemsJournal of Experimental Biology 211:1792–1804.https://doi.org/10.1242/jeb.017574

Regulation of mitochondrial dynamics and distribution by synapse position and neuronal activity in the axonEuropean Journal of Neuroscience 38:2350–2363.https://doi.org/10.1111/ejn.12263

Sparse coding of sensory inputsCurrent Opinion in Neurobiology 14:481–487.https://doi.org/10.1016/j.conb.2004.07.007

Two sides to longterm potentiation: a view towards reconciliationPhilosophical Transactions of the Royal Society B: Biological Sciences 369:20130154.https://doi.org/10.1098/rstb.2013.0154

How the optic nerve allocates space, energy capacity, and informationJournal of Neuroscience 29:7917–7928.https://doi.org/10.1523/JNEUROSCI.520008.2009

The perceptron: a probabilistic model for information storage and organization in the brainPsychological Review 65:386–408.https://doi.org/10.1037/h0042519

Efficient partitioning of memory systems and its importance for memory consolidationPLOS Computational Biology 9:e1003146.https://doi.org/10.1371/journal.pcbi.1003146

ConferenceDendritic cortical microcircuits approximate the backpropagation algorithmAdvances in Neural Information Processing Systems. pp. 8721–8732.

Synaptic weight set by Munc131 supramolecular assembliesNature Neuroscience 21:41–49.https://doi.org/10.1038/s4159301700419

Central synapses release a resourceefficient amount of glutamateNature Neuroscience 16:10–12.https://doi.org/10.1038/nn.3285

SoftwarePresynaptic Stochasticity, version swh:1:rev:de0851773cd1375b885dcdb18e711a2fb6eb06a4Software Heritage.

Action potential energy efficiency varies among neuron types in vertebrates and invertebratesPLO Computational Biology 6:e1000840.https://doi.org/10.1371/journal.pcbi.1000840

Balanced excitatory and inhibitory synaptic currents promote efficient coding and metabolic efficiencyPLOS Computational Biology 9:e1003263.https://doi.org/10.1371/journal.pcbi.1003263

A mathematical theory of communicationBell System Technical Journal 27:379–423.https://doi.org/10.1002/j.15387305.1948.tb01338.x

Regularization of neural networks using dropconnectNeural Networks 110:82–90.https://doi.org/10.1016/j.neunet.2018.09.009

Using goaldriven deep learning models to understand sensory cortexNature Neuroscience 19:356–365.https://doi.org/10.1038/nn.4244

Presynaptic longterm plasticityFrontiers in Synaptic Neuroscience 5:8.https://doi.org/10.3389/fnsyn.2013.00008
Decision letter

Timothy E BehrensSenior Editor; University of Oxford, United Kingdom

Timothy O'LearyReviewing Editor; University of Cambridge, United Kingdom

JeanPascal PfisterReviewer
Our editorial process produces two outputs: i) public reviews designed to be posted alongside the preprint for the benefit of readers; ii) feedback on the manuscript for the authors, including requests for revisions, shown below. We also include an acceptance summary that explains what the editors found interesting or important about the work.
Acceptance summary:
In many nervous systems such as mammalian cortex excitatory synapses are stochastic and the probability of release of neurotransmitter can be modulated by plasticity and neural activity. This paper presents a simple biologically plausible mechanism that regulates the probability of release during learning. Using network simulations the authors show that this can result in more energy efficient processing of learned stimuli by enhancing the reliability of important connections, with lower expected rates of transmission at less important synapses.
Decision letter after peer review:
Thank you for submitting your article "Presynaptic Stochasticity Improves Energy Efficiency and Alleviates the StabilityPlasticity Dilemma" for consideration by eLife. Your article has been reviewed by 2 peer reviewers, and the evaluation has been overseen by a Reviewing Editor and Timothy Behrens as the Senior Editor. The following individual involved in review of your submission has agreed to reveal their identity: JeanPascal Pfister (Reviewer #3).
The reviewers have discussed their reviews with one another, and the Reviewing Editor has drafted this to help you prepare a revised submission.
Essential revisions:
1) Plasticity in p(release) is a nice idea whose simplicity suggests that it is biologically plausible. However, the clear gap in the study is relating the proposed model to the wealth of data on how LTP/D mechanism affect release probabilities. The authors should do more work to survey these mechanisms and, if possible, show how they might relate to the proposed plasticity mechanism or something similar.
2) The generic nature of the networks and simulations is fine but it would be nice in the discussion to suggest what kinds of networks one might expect such a mechanism to be at work.
3) The claim that this mechanism fully alleviates the stability/plasticity dilemma should be tempered: it can impact the tradeoff in specific cases and under broad assumptions may improve energy efficiency. The text should be revised appropriately.
4) Please include a response to the reviewers' comments below with the resubmission and address the specific points raised.
Reviewer #3 (Recommendations for the authors):
1. There are several freely available datasets on synaptic plasticity (the ones from Sjostrom is just one example). I would encourage the authors to test their novel learning rule on existing plasticity data sets.
2. I am surprised that the nice work of Fusi is not mentioned here. The cascade model of Fusi precisely proposes a multistate model for the synapse in order to alleviate the stabilityplasticity dilemma. From this perspective, the model proposed by the authors could be seen as a special case of the cascade model.
3. On Figure 2b, I would add an additional control. What happens if the lesioning targets first the lowest expected synaptic strength? Will it be closer to the blue line (Random Order) or the pink line (lowest probability first)?
https://doi.org/10.7554/eLife.69884.sa1Author response
Essential revisions:
1) Plasticity in p(release) is a nice idea whose simplicity suggests that it is biologically plausible. However, the clear gap in the study is relating the proposed model to the wealth of data on how LTP/D mechanism affect release probabilities. The authors should do more work to survey these mechanisms and, if possible, show how they might relate to the proposed plasticity mechanism or something similar.
We made two changes to relate the model to biological data on presynaptic LTP/D mechanisms. Firstly, in the discussion, we more thoroughly review how individual components of our model relate to known plasticity mechanisms, see subsection “Presynaptic LongTerm Plasticity”. Secondly, we analyse a synaptic plasticity dataset by Sjöström et al., showing some evidence for our stabilisation mechanism, see subsection “Link between Presynaptic Release and Stability”, where we also discuss additional qualitative evidence.
2) The generic nature of the networks and simulations is fine but it would be nice in the discussion to suggest what kinds of networks one might expect such a mechanism to be at work.
We expanded the discussion, explaining where and why the proposed mechanisms could contribute to both energyefficient processing and lifelong learning, see subsection “Correspondence to Biological Networks”.
3) The claim that this mechanism fully alleviates the stability/plasticity dilemma should be tempered: it can impact the tradeoff in specific cases and under broad assumptions may improve energy efficiency. The text should be revised appropriately.
We updated parts of the title and abstract and went over the remainder of the manuscript to make sure that the claims are tempered.
4) Please include a response to the reviewers' comments below with the resubmission and address the specific points raised.
See detailed comments below.
Reviewer #3 (Recommendations for the authors):
1. There are several freely available datasets on synaptic plasticity (the ones from Sjostrom is just one example). I would encourage the authors to test their novel learning rule on existing plasticity data sets.
We added an analysis of a synaptic plasticity dataset by Sjöström et al., (2001), see discussion subsection “Link between Presynaptic Release and Stability” and Figure 9. The analysis is consistent with a key property of our model, namely that synapses with high release probability are more stable than ones with low release probability.
2. I am surprised that the nice work of Fusi is not mentioned here. The cascade model of Fusi precisely proposes a multistate model for the synapse in order to alleviate the stabilityplasticity dilemma. From this perspective, the model proposed by the authors could be seen as a special case of the cascade model.
Thanks for pointing out this oversight, we agree that this is relevant work. We updated the discussion accordingly, see subsection “Related Synapse Models”.
3. On Figure 2b, I would add an additional control. What happens if the lesioning targets first the lowest expected synaptic strength? Will it be closer to the blue line (Random Order) or the pink line (lowest probability first)?
We added this control. Keeping “high energy (expected strength)” synapses is even more important for the network than keeping “high release probability synapses”. Nevertheless, the claim that release probabilities are related to importance holds true, and our analysis also shows that release probabilities are more closely related to the Fisher information (which is a more local measure than the lesion experiment) than to the expected strength.
https://doi.org/10.7554/eLife.69884.sa2Article and author information
Author details
Funding
Swiss National Science Foundation (PZ00P318602)
 Simon Schug
Swiss National Science Foundation (CRSII5_173721)
 Frederik Benzing
 Angelika Steger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Acknowledgements
We thank João Sacramento and Mark van Rossum for stimulating discussions and helpful comments.
Senior Editor
 Timothy E Behrens, University of Oxford, United Kingdom
Reviewing Editor
 Timothy O'Leary, University of Cambridge, United Kingdom
Reviewer
 JeanPascal Pfister
Publication history
 Received: April 28, 2021
 Preprint posted: May 5, 2021 (view preprint)
 Accepted: October 18, 2021
 Accepted Manuscript published: October 18, 2021 (version 1)
 Version of Record published: December 29, 2021 (version 2)
Copyright
© 2021, Schug et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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