Understanding spontaneous transitions between dynamical modes in a network is of significant importance. These transitions may separate pathological and normal functions of the brain. In this paper, we develop a set of measures that, based on spatio-temporal features of network activity, predict autonomous network transitions from asynchronous to synchronous dynamics under various conditions. These metrics quantify spike-timing distributions within a narrow time window as a function of the relative location of the active neurons. We applied these metrics to investigate the properties of these transitions in excitatory-only and excitatory-and-inhibitory networks and elucidate how network topology, noise level, and cellular heterogeneity affect both the reliability and the timeliness of the predictions. The developed measures can be calculated in real time and therefore potentially applied in clinical situations.
Many networks are embedded in physical space and often interact with it. This interaction can be exemplified through constraints exerted on network topology, or through interactions of processes defined on a network with those that are linked to the space that the network is embedded within, leading to complex dynamics. Here we discuss an example of such an interaction in which a signaling agent is actively transported through the network edges and, at the same time, spreads passively through space due to diffusion. We show that these two processes cooperate or compete depending on the network topology leading to complex dynamics.
A period of sleep over the first few hours following single-trial contextual fear conditioning (CFC) is essential for hippocampally-mediated memory consolidation. Recent studies have uncovered intracellular mechanisms required for memory formation which are affected by post-conditioning sleep and sleep deprivation. However, almost nothing is known about the circuit-level activity changes during sleep that underlie activation of these intracellular pathways. Here we continuously recorded from the CA1 region of freely-behaving mice to characterize neuronal and network activity changes occurring during active memory consolidation. C57BL/6J mice were implanted with custom stereotrode recording arrays to monitor activity of individual CA1 neurons, local field potentials (LFPs), and electromyographic activity. Sleep architecture and state-specific CA1 activity patterns were assessed during a 24 h baseline recording period, and for 24 h following either single-trial CFC or Sham conditioning. We find that consolidation of CFC is not associated with significant sleep architecture changes, but is accompanied by long-lasting increases in CA1 neuronal firing, as well as increases in delta, theta, and gamma-frequency CA1 LFP activity. These changes occurred in both sleep and wakefulness, and may drive synaptic plasticity within the hippocampus during memory formation. We also find that functional connectivity within the CA1 network, assessed through functional clustering algorithm (FCA) analysis of spike timing relationships among recorded neurons, becomes more stable during consolidation of CFC. This increase in network stability was not present following Sham conditioning, was most evident during post-CFC slow wave sleep (SWS), and was negligible during post-CFC wakefulness. Thus in the interval between encoding and recall, SWS may stabilize the hippocampal contextual fear memory (CFM) trace by promoting CA1 network stability.
synaptic plasticity; fear memory; neural network; consolidation; hippocampus; extracellular recording; slow wave sleep; REM sleep
Although sleep is a fundamental behavior observed in virtually all animal species, its functions remain unclear. One leading proposal, known as the synaptic renormalization hypothesis, suggests that sleep is necessary to counteract a global strengthening of synapses that occurs during wakefulness. Evidence for sleep-dependent synaptic downscaling (or synaptic renormalization) has been observed experimentally, but the physiological mechanisms which generate this phenomenon are unknown. In this study, we propose that changes in neuronal membrane excitability induced by acetylcholine may provide a dynamical mechanism for both wake-dependent synaptic upscaling and sleep-dependent downscaling. We show in silico that cholinergically-induced changes in network firing patterns alter overall network synaptic potentiation when synaptic strengths evolve through spike-timing dependent plasticity mechanisms. Specifically, network synaptic potentiation increases dramatically with high cholinergic concentration and decreases dramatically with low levels of acetylcholine. We demonstrate that this phenomenon is robust across variation of many different network parameters.
The function of sleep is one of the greatest mysteries in contemporary neuroscience. Nearly every species of animal requires it, yet we do not know why. One idea, known as the synaptic renormalization hypothesis, suggests that waking results in a global increase in the strengths of connections in the brain, a phenomenon which is unsustainable because stronger connections consume more energy and take up more space. The function of sleep, according to this hypothesis, is to downscale or “renormalize” connection strengths. While mounting experimental evidence confirms that sleep-dependent synaptic downscaling does occur, we still do not know what biophysical mechanism causes it. In this paper, we show computational results which indicate that the neuromodulator acetylcholine may have a key role to play in sleep-dependent synaptic downscaling. If confirmed experimentally, these findings will help to unravel the mystery of sleep.
Spatiotemporal pattern formation in neuronal networks depends on the interplay between cellular and network synchronization properties. The neuronal phase response curve (PRC) is an experimentally obtainable measure that characterizes the cellular response to small perturbations, and can serve as an indicator of cellular propensity for synchronization. Two broad classes of PRCs have been identified for neurons: Type I, in which small excitatory perturbations induce only advances in firing, and Type II, in which small excitatory perturbations can induce both advances and delays in firing. Interestingly, neuronal PRCs are usually attenuated with increased spiking frequency, and Type II PRCs typically exhibit a greater attenuation of the phase delay region than of the phase advance region. We found that this phenomenon arises from an interplay between the time constants of active ionic currents and the interspike interval. As a result, excitatory networks consisting of neurons with Type I PRCs responded very differently to frequency modulation compared to excitatory networks composed of neurons with Type II PRCs. Specifically, increased frequency induced a sharp decrease in synchrony of networks of Type II neurons, while frequency increases only minimally affected synchrony in networks of Type I neurons. These results are demonstrated in networks in which both types of neurons were modeled generically with the Morris-Lecar model, as well as in networks consisting of Hodgkin-Huxley-based model cortical pyramidal cells in which simulated effects of acetylcholine changed PRC type. These results are robust to different network structures, synaptic strengths and modes of driving neuronal activity, and they indicate that Type I and Type II excitatory networks may display two distinct modes of processing information.
Synchronization of the firing of neurons in the brain is related to many cognitive functions, such as recognizing faces, discriminating odors, and coordinating movement. It is therefore important to understand what properties of neuronal networks promote synchrony of neural firing. One measure that is often used to determine the contribution of individual neurons to network synchrony is called the phase response curve (PRC). PRCs describe how the timing of neuronal firing changes depending on when input, such as a synaptic signal, is received by the neuron. A characteristic of PRCs that has previously not been well understood is that they change dramatically as the neuron's firing frequency is modulated. This effect carries potential significance, since cognitive functions are often associated with specific frequencies of network activity in the brain. We showed computationally that the frequency dependence of PRCs can be explained by the relative timing of ionic membrane currents with respect to the time between spike firings. Our simulations also showed that the frequency dependence of neuronal PRCs leads to frequency-dependent changes in network synchronization that can be different for different neuron types. These results further our understanding of how synchronization is generated in the brain to support various cognitive functions.
We describe a novel mechanism that mediates the rapid and selective pattern formation of neuronal network activity in response to changing correlations of sub-threshold level input. The mechanism is based on the classical resonance and experimentally observed phenomena that the resonance frequency of a neuron shifts as a function of membrane depolarization. As the neurons receive varying sub-threshold input, their natural frequency is shifted in and out of its resonance range. In response, the neuron fires a sequence of action potentials, corresponding to the specific values of signal currents, in a highly organized manner. We show that this mechanism provides for the selective activation and phase locking of the cells in the network, underlying input-correlated spatio-temporal pattern formation, and could be the basis for reliable spike-timing dependent plasticity. We compare the selectivity and efficiency of this pattern formation to a supra-threshold network activation and a non-resonating network/neuron model to demonstrate that the resonance mechanism is the most effective. Finally we show that this process might be the basis of the phase precession phenomenon observed during firing of hippocampal place cells, and that it may underlie the active switching of neuronal networks to locking at various frequencies.
Interneurons coupled by both electrical gap-junctions (GJs) and chemical GABAergic synapses are major components of forebrain networks. However, their contributions to the generation of specific activity patterns, and their overall contributions to network function, remain poorly understood. Here we demonstrate, using computational methods, that the topological properties of interneuron networks can elicit a wide range of activity dynamics, and either prevent or permit local pattern formation. We systematically varied the topology of GJ and inhibitory chemical synapses within simulated networks, by changing connection types from local to random, and changing the total number of connections. As previously observed we found that randomly coupled GJs lead to globally synchronous activity. In contrast, we found that local GJ connectivity may govern the formation of highly spatially heterogeneous activity states. These states are inherently temporally unstable when the input is uniformly random, but can rapidly stabilize when the network detects correlations or asymmetries in the inputs. We show a correspondence between this feature of network activity and experimental observations of transient stabilization of striatal fast-spiking interneurons (FSIs), in electrophysiological recordings from rats performing a simple decision-making task. We suggest that local GJ coupling enables an active search-and-select function of striatal FSIs, which contributes to the overall role of cortical-basal ganglia circuits in decision-making.
Hippocampal-neocortical interactions are key to the rapid formation of novel associative memories in the hippocampus and consolidation to long term storage sites in the neocortex. We investigated the role of network correlates during information processing in hippocampal-cortical networks. We found that changes in the intrinsic network dynamics due to the formation of structural network heterogeneities alone act as a dynamical and regulatory mechanism for stimulus novelty and familiarity detection, thereby controlling memory management in the context of memory consolidation. This network dynamic, coupled with an anatomically established feedback between the hippocampus and the neocortex, recovered heretofore unexplained properties of neural activity patterns during memory management tasks which we observed during sleep in multiunit recordings from behaving animals. Our simple dynamical mechanism shows an experimentally matched progressive shift of memory activation from the hippocampus to the neocortex and thus provides the means to achieve an autonomous off-line progression of memory consolidation.
Spatiotemporal patterning of neuronal activity is considered to be an important feature of cognitive processing in the brain as well as pathological brain states, such as seizures. Here, we investigate complex interactions between intrinsic properties of neurons and network structure in the generation of network spatiotemporal patterning in the context of seizure-like synchrony. We show that membrane excitability properties have differential effects on network activity patterning for different network topologies. We consider excitatory networks consisting of neurons with excitability properties varying between type I and type II that exhibit significantly different spike frequency responses to external current stimulation, especially at firing threshold. We find that networks with type II-like neurons show higher synchronization and bursting capacity across a range of network topologies than corresponding networks with type I-like neurons. These differences in activity patterning are persistent across different network sizes, connectivity strengths, magnitudes of random external input, and the addition of inhibitory interneurons to the network, making them highly likely to be relevant to brain function. Furthermore, we show that heterogeneous networks of mixed cell types show emergent dynamical patterns even for very low mixing ratios. Specifically, the addition of a small percentage of type II-like cells into a network of type I-like cells can markedly change the patterning of network activity. These findings suggest that cellular as well as network mechanisms can go hand in hand, leading to the generation of seizure-like discharges, suggesting that a single ictogenic mechanism alone may not be responsible for seizure generation.
network structure; spatiotemporal pattern formation; synchrony; network dynamics; ictogenesis; cellular excitability
We propose a novel measure to detect temporal ordering in the activity of individual neurons in a local network, which is thought to be a hallmark of activity-dependent synaptic modifications during learning. The measure, called Causal Entropy, is based on the time-adaptive detection of asymmetries in the relative temporal patterning between neuronal pairs. We characterize properties of the measure on both simulated data and experimental multiunit recordings of hippocampal neurons from the awake, behaving rat, and show that the metric can more readily detect those asymmetries than standard cross correlation-based techniques, especially since the temporal sensitivity of causal entropy can detect such changes rapidly and dynamically.
temporal pattern formation; multi-unit recording; hippocampal CA1; long term potentiation; asymmetric correlation