The amygdala responds to a large variety of socially and emotionally salient environmental and interoceptive stimuli. The context in which these stimuli occur determines their social and emotional significance. In canonical neurophysiological studies, the fast-paced succession of stimuli and events induce phasic changes in neural activity. During inter-trial intervals, neural activity is expected to return to a stable and featureless level of spontaneous activity, often called baseline. In previous studies we found that context, such as the presence of a social partner, induces brain states that can transcend the fast-paced succession of stimuli and can be recovered from the spontaneous, inter-trial firing rate of neurons. Indeed, the spontaneous firing rates of neurons in the amygdala are different during blocks of gentle grooming touches delivered by a trusted social partner, and during blocks of non-social airflow stimuli delivered by a computer-controlled air valve. Here, we examine local field potentials (LFPs) recorded during periods of spontaneous activity to determine whether information about context can be extracted from these signals. We found that information about social vs. non-social context is present in the local field potential during periods of spontaneous activity between the application of grooming and airflow stimuli, as machine learning techniques can reliably decode context from spectrograms of spontaneous LFPs. No significant differences were detected between the nuclei of the amygdala that receive direct or indirect inputs from areas of the prefrontal cortex known to coordinate flexible, context-dependent behaviors. The lack of nuclear specificity suggests that context-related synaptic inputs arise from a shared source, possibly interoceptive inputs, that signal the physiological state of the body during social and non-social blocks of tactile stimulation.

Constraining the many biological parameters that govern cortical dynamics is computationally and conceptually difficult because of the curse of dimensionality. This paper addresses these challenges by proposing (1) a novel data-informed mean-field (MF) approach to efficiently map the parameter space of network models; and (2) an organizing principle for studying parameter space that enables the extraction biologically meaningful relations from this high-dimensional data. We illustrate these ideas using a large-scale network model of the Macaque primary visual cortex. Of the 10-20 model parameters, we identify 7 that are especially poorly constrained, and use the MF algorithm in (1) to discover the firing rate contours in this 7D parameter cube. Defining a "biologically plausible" region to consist of parameters that exhibit spontaneous Excitatory and Inhibitory firing rates compatible with experimental values, we find that this region is a slightly thickened codimension-1 submanifold. An implication of this finding is that while plausible regimes depend sensitively on parameters, they are also robust and flexible provided one compensates appropriately when parameters are varied. Our organizing principle for conceptualizing parameter dependence is to focus on certain 2D parameter planes that govern lateral inhibition: Intersecting these planes with the biologically plausible region leads to very simple geometric structures which, when suitably scaled, have a universal character independent of where the intersections are taken. In addition to elucidating the geometry of the plausible region, this invariance suggests useful approximate scaling relations. Our study offers, for the first time, a complete characterization of the set of all biologically plausible parameters for a detailed cortical model, which has been out of reach due to the high dimensionality of parameter space.

Highly connected recurrent neural networks often produce chaotic dynamics, meaning their precise activity is sensitive to small perturbations. What are the consequences of chaos for how such networks encode streams of temporal stimuli? On the one hand, chaos is a strong source of randomness, suggesting that small changes in stimuli will be obscured by intrinsically generated variability. On the other hand, recent work shows that the type of chaos that occurs in spiking networks can have a surprisingly low-dimensional structure, suggesting that there may be room for fine stimulus features to be precisely resolved. Here we show that strongly chaotic networks produce patterned spikes that reliably encode time-dependent stimuli: using a decoder sensitive to spike times on timescales of 10's of ms, one can easily distinguish responses to very similar inputs. Moreover, recurrence serves to distribute signals throughout chaotic networks so that small groups of cells can encode substantial information about signals arriving elsewhere. A conclusion is that the presence of strong chaos in recurrent networks need not exclude precise encoding of temporal stimuli via spike patterns.

MOTIVATION: Time-course gene expression datasets provide important insights into dynamic aspects of biological processes, such as circadian rhythms, cell cycle and organ development. In a typical microarray time-course experiment, measurements are obtained at each time point from multiple replicate samples. Accurately recovering the gene expression patterns from experimental observations is made challenging by both measurement noise and variation among replicates' rates of development. Prior work on this topic has focused on inference of expression patterns assuming that the replicate times are synchronized. We develop a statistical approach that simultaneously infers both (i) the underlying (hidden) expression profile for each gene, as well as (ii) the biological time for each individual replicate. Our approach is based on Gaussian process regression (GPR) combined with a probabilistic model that accounts for uncertainty about the biological development time of each replicate. RESULTS: We apply GPR with uncertain measurement times to a microarray dataset of mRNA expression for the hair-growth cycle in mouse back skin, predicting both profile shapes and biological times for each replicate. The predicted time shifts show high consistency with independently obtained morphological estimates of relative development. We also show that the method systematically reduces prediction error on out-of-sample data, significantly reducing the mean squared error in a cross-validation study. AVAILABILITY: Matlab code for GPR with uncertain time shifts is available at http://sli.ics.uci.edu/Code/GPRTimeshift/ CONTACT: [email protected].

MOTIVATION: Cyclical biological processes such as cell division and circadian regulation produce coordinated periodic expression of thousands of genes. Identification of such genes and their expression patterns is a crucial step in discovering underlying regulatory mechanisms. Existing computational methods are biased toward discovering genes that follow sine-wave patterns. RESULTS: We present an analysis of variance (ANOVA) periodicity detector and its Bayesian extension that can be used to discover periodic transcripts of arbitrary shapes from replicated gene expression profiles. The models are applicable when the profiles are collected at comparable time points for at least two cycles. We provide an empirical Bayes procedure for estimating parameters of the prior distributions and derive closed-form expressions for the posterior probability of periodicity, enabling efficient computation. The model is applied to two datasets profiling circadian regulation in murine liver and skeletal muscle, revealing a substantial number of previously undetected non-sinusoidal periodic transcripts in each. We also apply quantitative real-time PCR to several highly ranked non-sinusoidal transcripts in liver tissue found by the model, providing independent evidence of circadian regulation of these genes. AVAILABILITY: Matlab software for estimating prior distributions and performing inference is available for download from http://www.datalab.uci.edu/resources/periodicity/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Clustering is an important analysis performed on microarray gene expression data since it groups genes which have similar expression patterns and enables the exploration of unknown gene functions. Microarray experiments are associated with many sources of experimental and biological variation and the resulting gene expression data are therefore very noisy. Many heuristic and model-based clustering approaches have been developed to cluster this noisy data. However, few of them include consideration of probe-level measurement error which provides rich information about technical variability. RESULTS: We augment a standard model-based clustering method to incorporate probe-level measurement error. Using probe-level measurements from a recently developed Affymetrix probe-level model, multi-mgMOS, we include the probe-level measurement error directly into the standard Gaussian mixture model. Our augmented model is shown to provide improved clustering performance on simulated datasets and a real mouse time-course dataset. CONCLUSION: The performance of model-based clustering of gene expression data is improved by including probe-level measurement error and more biologically meaningful clustering results are obtained.