Flexible neural connectivity under constraints on total connection strength.

Neural computation is determined by neurons' dynamics and circuit connectivity. Uncertain and dynamic environments may require neural hardware to adapt to different computational tasks, each requiring different connectivity configurations. At the same time, connectivity is subject to a variety of constraints, placing limits on the possible computations a given neural circuit can perform. Here we examine the hypothesis that the organization of neural circuitry favors computational flexibility: that it makes many computational solutions available, given physiological constraints. From this hypothesis, we develop models of connectivity degree distributions based on constraints on a neuron's total synaptic weight. To test these models, we examine reconstructions of the mushroom bodies from the first instar larva and adult Drosophila melanogaster. We perform a Bayesian model comparison for two constraint models and a random wiring null model. Overall, we find that flexibility under a homeostatically fixed total synaptic weight describes Kenyon cell connectivity better than other models, suggesting a principle shaping the apparently random structure of Kenyon cell wiring. Furthermore, we find evidence that larval Kenyon cells are more flexible earlier in development, suggesting a mechanism whereby neural circuits begin as flexible systems that develop into specialized computational circuits.

Dimensionality in recurrent spiking networks: Global trends in activity and local origins in connectivity.

The dimensionality of a network's collective activity is of increasing interest in neuroscience. This is because dimensionality provides a compact measure of how coordinated network-wide activity is, in terms of the number of modes (or degrees of freedom) that it can independently explore. A low number of modes suggests a compressed low dimensional neural code and reveals interpretable dynamics [1], while findings of high dimension may suggest flexible computations [2, 3]. Here, we address the fundamental question of how dimensionality is related to connectivity, in both autonomous and stimulus-driven networks. Working with a simple spiking network model, we derive three main findings. First, the dimensionality of global activity patterns can be strongly, and systematically, regulated by local connectivity structures. Second, the dimensionality is a better indicator than average correlations in determining how constrained neural activity is. Third, stimulus evoked neural activity interacts systematically with neural connectivity patterns, leading to network responses of either greater or lesser dimensionality than the stimulus.

Training and Spontaneous Reinforcement of Neuronal Assemblies by Spike Timing Plasticity.

The synaptic connectivity of cortex is plastic, with experience shaping the ongoing interactions between neurons. Theoretical studies of spike timing-dependent plasticity (STDP) have focused on either just pairs of neurons or large-scale simulations. A simple analytic account for how fast spike time correlations affect both microscopic and macroscopic network structure is lacking. We develop a low-dimensional mean field theory for STDP in recurrent networks and show the emergence of assemblies of strongly coupled neurons with shared stimulus preferences. After training, this connectivity is actively reinforced by spike train correlations during the spontaneous dynamics. Furthermore, the stimulus coding by cell assemblies is actively maintained by these internally generated spiking correlations, suggesting a new role for noise correlations in neural coding. Assembly formation has often been associated with firing rate-based plasticity schemes; our theory provides an alternative and complementary framework, where fine temporal correlations and STDP form and actively maintain learned structure in cortical networks.

Linking structure and activity in nonlinear spiking networks.

Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks' spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities-including those of different cell types-combine with connectivity to shape population activity and function.

Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses.

The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure.

Kv7 channels regulate pairwise spiking covariability in health and disease.

Low-threshold M currents are mediated by the Kv7 family of potassium channels. Kv7 channels are important regulators of spiking activity, having a direct influence on the firing rate, spike time variability, and filter properties of neurons. How Kv7 channels affect the joint spiking activity of populations of neurons is an important and open area of study. Using a combination of computational simulations and analytic calculations, we show that the activation of Kv7 conductances reduces the covariability between spike trains of pairs of neurons driven by common inputs. This reduction is beyond that explained by the lowering of firing rates and involves an active cancellation of common fluctuations in the membrane potentials of the cell pair. Our theory shows that the excess covariance reduction is due to a Kv7-induced shift from low-pass to band-pass filtering of the single neuron spike train response. Dysfunction of Kv7 conductances is related to a number of neurological diseases characterized by both elevated firing rates and increased network-wide correlations. We show how changes in the activation or strength of Kv7 conductances give rise to excess correlations that cannot be compensated for by synaptic scaling or homeostatic modulation of passive membrane properties. In contrast, modulation of Kv7 activation parameters consistent with pharmacological treatments for certain hyperactivity disorders can restore normal firing rates and spiking correlations. Our results provide key insights into how regulation of a ubiquitous potassium channel class can control the coordination of population spiking activity.

Metastability in networks of nonlinear stochastic integrate-and-fire neurons.

Neurons in the brain continuously process the barrage of sensory inputs they receive from the environment. A wide array of experimental work has shown that the collective activity of neural populations encodes and processes this constant bombardment of information. How these collective patterns of activity depend on single neuron properties is often unclear. Single-neuron recordings have shown that individual neural responses to inputs are nonlinear, which prevents a straightforward extrapolation from single neuron features to emergent collective states. In this work, we use a field theoretic formulation of a stochastic leaky integrate-and-fire model to study the impact of nonlinear intensity functions on macroscopic network activity. We show that the interplay between nonlinear spike emission and membrane potential resets can i) give rise to metastable transitions between active firing rate states, and ii) can enhance or suppress mean firing rates and membrane potentials in opposite directions.

VIP interneurons in mouse primary visual cortex selectively enhance responses to weak but specific stimuli.

Vasoactive intestinal peptide-expressing (VIP) interneurons in the cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Although VIP neuron activity in the primary visual cortex (V1) of mouse is highly correlated with locomotion, the relevance of locomotion-related VIP neuron activity to visual coding is not known. Here we show that VIP neurons in mouse V1 respond strongly to low contrast front-to-back motion that is congruent with self-motion during locomotion but are suppressed by other directions and contrasts. VIP and SST neurons have complementary contrast tuning. Layer 2/3 contains a substantially larger population of low contrast preferring pyramidal neurons than deeper layers, and layer 2/3 (but not deeper layer) pyramidal neurons show bias for front-to-back motion specifically at low contrast. Network modeling indicates that VIP-SST mutual antagonism regulates the gain of the cortex to achieve sensitivity to specific weak stimuli without compromising network stability.

Attentional modulation of neuronal variability in circuit models of cortex.

The circuit mechanisms behind shared neural variability (noise correlation) and its dependence on neural state are poorly understood. Visual attention is well-suited to constrain cortical models of response variability because attention both increases firing rates and their stimulus sensitivity, as well as decreases noise correlations. We provide a novel analysis of population recordings in rhesus primate visual area V4 showing that a single biophysical mechanism may underlie these diverse neural correlates of attention. We explore model cortical networks where top-down mediated increases in excitability, distributed across excitatory and inhibitory targets, capture the key neuronal correlates of attention. Our models predict that top-down signals primarily affect inhibitory neurons, whereas excitatory neurons are more sensitive to stimulus specific bottom-up inputs. Accounting for trial variability in models of state dependent modulation of neuronal activity is a critical step in building a mechanistic theory of neuronal cognition.

From the statistics of connectivity to the statistics of spike times in neuronal networks.

An essential step toward understanding neural circuits is linking their structure and their dynamics. In general, this relationship can be almost arbitrarily complex. Recent theoretical work has, however, begun to identify some broad principles underlying collective spiking activity in neural circuits. The first is that local features of network connectivity can be surprisingly effective in predicting global statistics of activity across a network. The second is that, for the important case of large networks with excitatory-inhibitory balance, correlated spiking persists or vanishes depending on the spatial scales of recurrent and feedforward connectivity. We close by showing how these ideas, together with plasticity rules, can help to close the loop between network structure and activity statistics.