Berlin : A. Hirschwald, 1873.

Leipzig : P. Hobbing, 1890.

Edinburgh : J. Dunn, 1826.

[London] : E. & F.N. Spon, 1881.

London : H.K. Lewis, 1891.

Paris : G. Steinheil, 1893.

Stuttgart : G. Kroner, 1889.

London : Swan Sonnenschein, 1897.

Berlin : A. Hirschwald, 1896-1900.

Edinburgh : Oliver & Boyd, 1862.

A state law aimed at encouraging—or prodding—small, rural districts to merge has hit some speed bumps on the road to implementation.

A Paris (rue des deux portes, St André des arts no. 7) : chez Noel et c.ie, [1820?] ([Paris?] : Litho. de F. Noel)

[Spain?], An. 1817.

[Paris] : Calcographie du Louvre, Musées Imperiaux, [1849?]

One of the common tasks in unsupervised learning is dimensionality reduction, where the goal is to find meaningful low-dimensional structures hidden in high-dimensional data. Sometimes referred to as manifold learning, this problem is closely related to the problem of localization, which aims at embedding a weighted graph into a low-dimensional Euclidean space. Several methods have been proposed for localization, and also manifold learning. Nonetheless, the robustness property of most of them is little understood. In this paper, we obtain perturbation bounds for classical scaling and trilateration, which are then applied to derive performance bounds for Isomap, Landmark Isomap, and Maximum Variance Unfolding. A new perturbation bound for procrustes analysis plays a key role.

This paper considers a Bayesian approach to graph-based semi-supervised learning. We show that if the graph parameters are suitably scaled, the graph-posteriors converge to a continuum limit as the size of the unlabeled data set grows. This consistency result has profound algorithmic implications: we prove that when consistency holds, carefully designed Markov chain Monte Carlo algorithms have a uniform spectral gap, independent of the number of unlabeled inputs. Numerical experiments illustrate and complement the theory.

The wavelet scattering transform is an invariant and stable signal representation suitable for many signal processing and machine learning applications. We present the Kymatio software package, an easy-to-use, high-performance Python implementation of the scattering transform in 1D, 2D, and 3D that is compatible with modern deep learning frameworks, including PyTorch and TensorFlow/Keras. The transforms are implemented on both CPUs and GPUs, the latter offering a significant speedup over the former. The package also has a small memory footprint. Source code, documentation, and examples are available under a BSD license at https://www.kymat.io.

An important problem in the field of Topological Data Analysis is defining topological summaries which can be combined with traditional data analytic tools. In recent work Bubenik introduced the persistence landscape, a stable representation of persistence diagrams amenable to statistical analysis and machine learning tools. In this paper we generalise the persistence landscape to multiparameter persistence modules providing a stable representation of the rank invariant. We show that multiparameter landscapes are stable with respect to the interleaving distance and persistence weighted Wasserstein distance, and that the collection of multiparameter landscapes faithfully represents the rank invariant. Finally we provide example calculations and statistical tests to demonstrate a range of potential applications and how one can interpret the landscapes associated to a multiparameter module.

We consider the problem of estimating the latent structure of a social network based on the observed information diffusion events, or cascades, where the observations for a given cascade consist of only the timestamps of infection for infected nodes but not the source of the infection. Most of the existing work on this problem has focused on estimating a diffusion matrix without any structural assumptions on it. In this paper, we propose a novel model based on the intuition that an information is more likely to propagate among two nodes if they are interested in similar topics which are also prominent in the information content. In particular, our model endows each node with an influence vector (which measures how authoritative the node is on each topic) and a receptivity vector (which measures how susceptible the node is for each topic). We show how this node-topic structure can be estimated from the observed cascades, and prove the consistency of the estimator. Experiments on synthetic and real data demonstrate the improved performance and better interpretability of our model compared to existing state-of-the-art methods.

The horseshoe prior is frequently employed in Bayesian analysis of high-dimensional models, and has been shown to achieve minimax optimal risk properties when the truth is sparse. While optimization-based algorithms for the extremely popular Lasso and elastic net procedures can scale to dimension in the hundreds of thousands, algorithms for the horseshoe that use Markov chain Monte Carlo (MCMC) for computation are limited to problems an order of magnitude smaller. This is due to high computational cost per step and growth of the variance of time-averaging estimators as a function of dimension. We propose two new MCMC algorithms for computation in these models that have significantly improved performance compared to existing alternatives. One of the algorithms also approximates an expensive matrix product to give orders of magnitude speedup in high-dimensional applications. We prove guarantees for the accuracy of the approximate algorithm, and show that gradually decreasing the approximation error as the chain extends results in an exact algorithm. The scalability of the algorithm is illustrated in simulations with problem size as large as $N=5,000$ observations and $p=50,000$ predictors, and an application to a genome-wide association study with $N=2,267$ and $p=98,385$. The empirical results also show that the new algorithm yields estimates with lower mean squared error, intervals with better coverage, and elucidates features of the posterior that were often missed by previous algorithms in high dimensions, including bimodality of posterior marginals indicating uncertainty about which covariates belong in the model.

Kushal K. Dey, Sourabh Bhattacharya.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 222--266.

Abstract:
Transformation based Markov Chain Monte Carlo (TMCMC) was proposed by Dutta and Bhattacharya ( Statistical Methodology 16 (2014) 100–116) as an efficient alternative to the Metropolis–Hastings algorithm, especially in high dimensions. The main advantage of this algorithm is that it simultaneously updates all components of a high dimensional parameter using appropriate move types defined by deterministic transformation of a single random variable. This results in reduction in time complexity at each step of the chain and enhances the acceptance rate. In this paper, we first provide a brief review of the optimal scaling theory for various existing MCMC approaches, comparing and contrasting them with the corresponding TMCMC approaches.The optimal scaling of the simplest form of TMCMC, namely additive TMCMC , has been studied extensively for the Gaussian proposal density in Dey and Bhattacharya (2017a). Here, we discuss diffusion-based optimal scaling behavior of additive TMCMC for non-Gaussian proposal densities—in particular, uniform, Student’s $t$ and Cauchy proposals. Although we could not formally prove our diffusion result for the Cauchy proposal, simulation based results lead us to conjecture that at least the recipe for obtaining general optimal scaling and optimal acceptance rate holds for the Cauchy case as well. We also consider diffusion based optimal scaling of TMCMC when the target density is discontinuous. Such non-regular situations have been studied in the case of Random Walk Metropolis Hastings (RWMH) algorithm by Neal and Roberts ( Methodology and Computing in Applied Probability 13 (2011) 583–601) using expected squared jumping distance (ESJD), but the diffusion theory based scaling has not been considered. We compare our diffusion based optimally scaled TMCMC approach with the ESJD based optimally scaled RWM with simulation studies involving several target distributions and proposal distributions including the challenging Cauchy proposal case, showing that additive TMCMC outperforms RWMH in almost all cases considered.

John J. Dziak, Donna L. Coffman, Matthew Reimherr, Justin Petrovich, Runze Li, Saul Shiffman, Mariya P. Shiyko.

Source: Statistics Surveys, Volume 13, 150--180.

Abstract:
Researchers are sometimes interested in predicting a distal or external outcome (such as smoking cessation at follow-up) from the trajectory of an intensively recorded longitudinal variable (such as urge to smoke). This can be done in a semiparametric way via scalar-on-function regression. However, the resulting fitted coefficient regression function requires special care for correct interpretation, as it represents the joint relationship of time points to the outcome, rather than a marginal or cross-sectional relationship. We provide practical guidelines, based on experience with scientific applications, for helping practitioners interpret their results and illustrate these ideas using data from a smoking cessation study.

Lutz Dümbgen, Markus Pauly, Thomas Schweizer.

Source: Statistics Surveys, Volume 9, 32--105.

Abstract:
This survey provides a self-contained account of $M$-estimation of multivariate scatter. In particular, we present new proofs for existence of the underlying $M$-functionals and discuss their weak continuity and differentiability. This is done in a rather general framework with matrix-valued random variables. By doing so we reveal a connection between Tyler’s (1987a) $M$-functional of scatter and the estimation of proportional covariance matrices. Moreover, this general framework allows us to treat a new class of scatter estimators, based on symmetrizations of arbitrary order. Finally these results are applied to $M$-estimation of multivariate location and scatter via multivariate $t$-distributions.

We propose a novel estimation procedure for scale-by-scale lead-lag relationships of financial assets observed at high-frequency in a non-synchronous manner. The proposed estimation procedure does not require any interpolation processing of original datasets and is applicable to those with highest time resolution available. Consistency of the proposed estimators is shown under the continuous-time framework that has been developed in our previous work Hayashi and Koike (2018). An empirical application to a quote dataset of the NASDAQ-100 assets identifies two types of lead-lag relationships at different time scales.

The paper focuses on a novel approach for false-positive reduction (FPR) of nodule candidates in Computer-aided detection (CADe) system after suspicious lesions proposing stage. Unlike common decisions in medical image analysis, the proposed approach considers input data not as 2d or 3d image, but as a point cloud and uses deep learning models for point clouds. We found out that models for point clouds require less memory and are faster on both training and inference than traditional CNN 3D, achieves better performance and does not impose restrictions on the size of the input image, thereby the size of the nodule candidate. We propose an algorithm for transforming 3d CT scan data to point cloud. In some cases, the volume of the nodule candidate can be much smaller than the surrounding context, for example, in the case of subpleural localization of the nodule. Therefore, we developed an algorithm for sampling points from a point cloud constructed from a 3D image of the candidate region. The algorithm guarantees to capture both context and candidate information as part of the point cloud of the nodule candidate. An experiment with creating a dataset from an open LIDC-IDRI database for a feature of the FPR task was accurately designed, set up and described in detail. The data augmentation technique was applied to avoid overfitting and as an upsampling method. Experiments are conducted with PointNet, PointNet++ and DGCNN. We show that the proposed approach outperforms baseline CNN 3D models and demonstrates 85.98 FROC versus 77.26 FROC for baseline models.

We present LCE, a Local Cascade Ensemble for traditional (tabular) multivariate data classification, and its extension LCEM for Multivariate Time Series (MTS) classification. LCE is a new hybrid ensemble method that combines an explicit boosting-bagging approach to handle the usual bias-variance tradeoff faced by machine learning models and an implicit divide-and-conquer approach to individualize classifier errors on different parts of the training data. Our evaluation firstly shows that the hybrid ensemble method LCE outperforms the state-of-the-art classifiers on the UCI datasets and that LCEM outperforms the state-of-the-art MTS classifiers on the UEA datasets. Furthermore, LCEM provides explainability by design and manifests robust performance when faced with challenges arising from continuous data collection (different MTS length, missing data and noise).

As an important type of reinforcement learning algorithms, actor-critic (AC) and natural actor-critic (NAC) algorithms are often executed in two ways for finding optimal policies. In the first nested-loop design, actor's one update of policy is followed by an entire loop of critic's updates of the value function, and the finite-sample analysis of such AC and NAC algorithms have been recently well established. The second two time-scale design, in which actor and critic update simultaneously but with different learning rates, has much fewer tuning parameters than the nested-loop design and is hence substantially easier to implement. Although two time-scale AC and NAC have been shown to converge in the literature, the finite-sample convergence rate has not been established. In this paper, we provide the first such non-asymptotic convergence rate for two time-scale AC and NAC under Markovian sampling and with actor having general policy class approximation. We show that two time-scale AC requires the overall sample complexity at the order of $mathcal{O}(epsilon^{-2.5}log^3(epsilon^{-1}))$ to attain an $epsilon$-accurate stationary point, and two time-scale NAC requires the overall sample complexity at the order of $mathcal{O}(epsilon^{-4}log^2(epsilon^{-1}))$ to attain an $epsilon$-accurate global optimal point. We develop novel techniques for bounding the bias error of the actor due to dynamically changing Markovian sampling and for analyzing the convergence rate of the linear critic with dynamically changing base functions and transition kernel.

Harnessing data to discover the underlying governing laws or equations that describe the behavior of complex physical systems can significantly advance our modeling, simulation and understanding of such systems in various science and engineering disciplines. Recent advances in sparse identification show encouraging success in distilling closed-form governing equations from data for a wide range of nonlinear dynamical systems. However, the fundamental bottleneck of this approach lies in the robustness and scalability with respect to data scarcity and noise. This work introduces a novel physics-informed deep learning framework to discover governing partial differential equations (PDEs) from scarce and noisy data for nonlinear spatiotemporal systems. In particular, this approach seamlessly integrates the strengths of deep neural networks for rich representation learning, automatic differentiation and sparse regression to approximate the solution of system variables, compute essential derivatives, as well as identify the key derivative terms and parameters that form the structure and explicit expression of the PDEs. The efficacy and robustness of this method are demonstrated on discovering a variety of PDE systems with different levels of data scarcity and noise. The resulting computational framework shows the potential for closed-form model discovery in practical applications where large and accurate datasets are intractable to capture.

Data-driven modelling and computational predictions based on maximum entropy principle (MaxEnt-principle) aim at finding as-simple-as-possible - but not simpler then necessary - models that allow to avoid the data overfitting problem. We derive a multivariate non-parametric and non-stationary formulation of the MaxEnt-principle and show that its solution can be approximated through a numerical maximisation of the sparse constrained optimization problem with regularization. Application of the resulting algorithm to popular financial benchmarks reveals memoryless models allowing for simple and qualitative descriptions of the major stock market indexes data. We compare the obtained MaxEnt-models to the heteroschedastic models from the computational econometrics (GARCH, GARCH-GJR, MS-GARCH, GARCH-PML4) in terms of the model fit, complexity and prediction quality. We compare the resulting model log-likelihoods, the values of the Bayesian Information Criterion, posterior model probabilities, the quality of the data autocorrelation function fits as well as the Value-at-Risk prediction quality. We show that all of the considered seven major financial benchmark time series (DJI, SPX, FTSE, STOXX, SMI, HSI and N225) are better described by conditionally memoryless MaxEnt-models with nonstationary regime-switching than by the common econometric models with finite memory. This analysis also reveals a sparse network of statistically-significant temporal relations for the positive and negative latent variance changes among different markets. The code is provided for open access.

Dimitris Bertsimas, Bart Van Parys.

Source: The Annals of Statistics, Volume 48, Number 1, 300--323.

Abstract:
We present a novel binary convex reformulation of the sparse regression problem that constitutes a new duality perspective. We devise a new cutting plane method and provide evidence that it can solve to provable optimality the sparse regression problem for sample sizes $n$ and number of regressors $p$ in the 100,000s, that is, two orders of magnitude better than the current state of the art, in seconds. The ability to solve the problem for very high dimensions allows us to observe new phase transition phenomena. Contrary to traditional complexity theory which suggests that the difficulty of a problem increases with problem size, the sparse regression problem has the property that as the number of samples $n$ increases the problem becomes easier in that the solution recovers 100% of the true signal, and our approach solves the problem extremely fast (in fact faster than Lasso), while for small number of samples $n$, our approach takes a larger amount of time to solve the problem, but importantly the optimal solution provides a statistically more relevant regressor. We argue that our exact sparse regression approach presents a superior alternative over heuristic methods available at present.

Didier Chételat, Martin T. Wells.

Source: The Annals of Statistics, Volume 47, Number 5, 2639--2670.

Abstract:
We study the behavior of a real $p$-dimensional Wishart random matrix with $n$ degrees of freedom when $n,p ightarrowinfty$ but $p/n ightarrow0$. We establish the existence of phase transitions when $p$ grows at the order $n^{(K+1)/(K+3)}$ for every $Kinmathbb{N}$, and derive expressions for approximating densities between every two phase transitions. To do this, we make use of a novel tool we call the $mathcal{F}$-conjugate of an absolutely continuous distribution, which is obtained from the Fourier transform of the square root of its density. In the case of the normalized Wishart distribution, this represents an extension of the $t$-distribution to the space of real symmetric matrices.

Mohamad Elmasri, Maxwell J. Farrell, T. Jonathan Davies, David A. Stephens.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 221--240.

Abstract:
Identifying undocumented or potential future interactions among species is a challenge facing modern ecologists. Recent link prediction methods rely on trait data; however, large species interaction databases are typically sparse and covariates are limited to only a fraction of species. On the other hand, evolutionary relationships, encoded as phylogenetic trees, can act as proxies for underlying traits and historical patterns of parasite sharing among hosts. We show that, using a network-based conditional model, phylogenetic information provides strong predictive power in a recently published global database of host-parasite interactions. By scaling the phylogeny using an evolutionary model, our method allows for biological interpretation often missing from latent variable models. To further improve on the phylogeny-only model, we combine a hierarchical Bayesian latent score framework for bipartite graphs that accounts for the number of interactions per species with host dependence informed by phylogeny. Combining the two information sources yields significant improvement in predictive accuracy over each of the submodels alone. As many interaction networks are constructed from presence-only data, we extend the model by integrating a correction mechanism for missing interactions which proves valuable in reducing uncertainty in unobserved interactions.

Seth Flaxman, Michael Chirico, Pau Pereira, Charles Loeffler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2564--2585.

Abstract:
We propose a generic spatiotemporal event forecasting method which we developed for the National Institute of Justice’s (NIJ) Real-Time Crime Forecasting Challenge (National Institute of Justice (2017)). Our method is a spatiotemporal forecasting model combining scalable randomized Reproducing Kernel Hilbert Space (RKHS) methods for approximating Gaussian processes with autoregressive smoothing kernels in a regularized supervised learning framework. While the smoothing kernels capture the two main approaches in current use in the field of crime forecasting, kernel density estimation (KDE) and self-exciting point process (SEPP) models, the RKHS component of the model can be understood as an approximation to the popular log-Gaussian Cox Process model. For inference, we discretize the spatiotemporal point pattern and learn a log-intensity function using the Poisson likelihood and highly efficient gradient-based optimization methods. Model hyperparameters including quality of RKHS approximation, spatial and temporal kernel lengthscales, number of autoregressive lags and bandwidths for smoothing kernels as well as cell shape, size and rotation, were learned using cross validation. Resulting predictions significantly exceeded baseline KDE estimates and SEPP models for sparse events.

Peter Bank, Yan Dolinsky.

Source: Bernoulli, Volume 26, Number 3, 2176--2201.

Abstract:
We prove a scaling limit theorem for the super-replication cost of options in a Cox–Ross–Rubinstein binomial model with transient price impact. The correct scaling turns out to keep the market depth parameter constant while resilience over fixed periods of time grows in inverse proportion with the duration between trading times. For vanilla options, the scaling limit is found to coincide with the one obtained by PDE-methods in ( Math. Finance 22 (2012) 250–276) for models with purely temporary price impact. These models are a special case of our framework and so our probabilistic scaling limit argument allows one to expand the scope of the scaling limit result to path-dependent options.

Yi Shen, Yizao Wang.

Source: Bernoulli, Volume 26, Number 1, 500--530.

Abstract:
We propose an aggregated random-field model, and investigate the scaling limits of the aggregated partial-sum random fields. In this model, each copy in the aggregation is a $pm 1$-valued random field built from two correlated one-dimensional random walks, the law of each determined by a random persistence parameter. A flexible joint distribution of the two parameters is introduced, and given the parameters the two correlated random walks are conditionally independent. For the aggregated random field, when the persistence parameters are independent, the scaling limit is a fractional Brownian sheet. When the persistence parameters are tail-dependent, characterized in the framework of multivariate regular variation, the scaling limit is more delicate, and in particular depends on the growth rates of the underlying rectangular region along two directions: at different rates different operator-scaling Gaussian random fields appear as the region area tends to infinity. In particular, at the so-called critical speed, a large family of Gaussian random fields with long-range dependence arise in the limit. We also identify four different regimes at non-critical speed where fractional Brownian sheets arise in the limit.

Fuhlbohm (Family)

Fuhlbohm (Family)

Matthew Moores, Geoff Nicholls, Anthony Pettitt, Kerrie Mengersen.

Source: Bayesian Analysis, Volume 15, Number 1, 1--27.

Abstract:
The inverse temperature parameter of the Potts model governs the strength of spatial cohesion and therefore has a major influence over the resulting model fit. A difficulty arises from the dependence of an intractable normalising constant on the value of this parameter and thus there is no closed-form solution for sampling from the posterior distribution directly. There is a variety of computational approaches for sampling from the posterior without evaluating the normalising constant, including the exchange algorithm and approximate Bayesian computation (ABC). A serious drawback of these algorithms is that they do not scale well for models with a large state space, such as images with a million or more pixels. We introduce a parametric surrogate model, which approximates the score function using an integral curve. Our surrogate model incorporates known properties of the likelihood, such as heteroskedasticity and critical temperature. We demonstrate this method using synthetic data as well as remotely-sensed imagery from the Landsat-8 satellite. We achieve up to a hundredfold improvement in the elapsed runtime, compared to the exchange algorithm or ABC. An open-source implementation of our algorithm is available in the R package bayesImageS .

Jacqueline J. Meulman, Anita J. van der Kooij, Kevin L. W. Duisters.

Source: Statistical Science, Volume 34, Number 3, 361--390.

Abstract:
We present a methodology for multiple regression analysis that deals with categorical variables (possibly mixed with continuous ones), in combination with regularization, variable selection and high-dimensional data ($Pgg N$). Regularization and optimal scaling (OS) are two important extensions of ordinary least squares regression (OLS) that will be combined in this paper. There are two data analytic situations for which optimal scaling was developed. One is the analysis of categorical data, and the other the need for transformations because of nonlinear relationships between predictors and outcome. Optimal scaling of categorical data finds quantifications for the categories, both for the predictors and for the outcome variables, that are optimal for the regression model in the sense that they maximize the multiple correlation. When nonlinear relationships exist, nonlinear transformation of predictors and outcome maximize the multiple correlation in the same way. We will consider a variety of transformation types; typically we use step functions for categorical variables, and smooth (spline) functions for continuous variables. Both types of functions can be restricted to be monotonic, preserving the ordinal information in the data. In combination with optimal scaling, three popular regularization methods will be considered: Ridge regression, the Lasso and the Elastic Net. The resulting method will be called ROS Regression (Regularized Optimal Scaling Regression). The OS algorithm provides straightforward and efficient estimation of the regularized regression coefficients, automatically gives the Group Lasso and Blockwise Sparse Regression, and extends them by the possibility to maintain ordinal properties in the data. Extended examples are provided.

02020-02-04: Burn Scars in Australia

Op-ed by Mr Claudio Borio, Head of the Monetary and Economic Department of the BIS, published in Il Sole 24 Ore, 8 November 2019.

The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M₂ or M₄ receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

SIGNIFICANCE STATEMENT The major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to speculation that the septo-hippocampal cholinergic projection contributing to theta oscillation. In this article, by long-term recording of MS cholinergic neurons, we found that they show a theta state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during slow-wave sleep could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M₂ and M₄ receptors.

Persistent alterations in neuronal activity elicit homeostatic plastic changes in synaptic transmission and/or intrinsic excitability. However, it is unknown whether these homeostatic processes operate in concert or at different temporal scales to maintain network activity around a set-point value. Here we show that chronic neuronal hyperactivity, induced by M-channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in cultured hippocampal pyramidal neurons from mice of either sex. Homeostatic changes of intrinsic excitability occurred at a fast timescale (1–4 h) and depended on ongoing spiking activity. This fast intrinsic adaptation included plastic changes in the threshold current and a distal relocation of FGF14, a protein physically bridging Na_v1.6 and K_v7.2 channels along the axon initial segment. In contrast, synaptic adaptations occurred at a slower timescale (~2 d) and involved decreases in miniature EPSC amplitude. To examine how these temporally distinct homeostatic responses influenced hippocampal network activity, we quantified the rate of spontaneous spiking measured by multielectrode arrays at extended timescales. M-Channel blockade triggered slow homeostatic renormalization of the mean firing rate (MFR), concomitantly accompanied by a slow synaptic adaptation. Thus, the fast intrinsic adaptation of excitatory neurons is not sufficient to account for the homeostatic normalization of the MFR. In striking contrast, homeostatic adaptations of intrinsic excitability and spontaneous MFR failed in hippocampal GABAergic inhibitory neurons, which remained hyperexcitable following chronic M-channel blockage. Our results indicate that a single perturbation such as M-channel inhibition triggers multiple homeostatic mechanisms that operate at different timescales to maintain network mean firing rate.

SIGNIFICANCE STATEMENT Persistent alterations in synaptic input elicit homeostatic plastic changes in neuronal activity. Here we show that chronic neuronal hyperexcitability, induced by M-type potassium channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in hippocampal excitatory neurons. The data indicate that the fast adaptation of intrinsic excitability depends on ongoing spiking activity but is not sufficient to provide homeostasis of the mean firing rate. Our results show that a single perturbation such as M-channel inhibition can trigger multiple homeostatic processes that operate at different timescales to maintain network mean firing rate.