Katsunori Kitano

Selective Participation of Somatodendritic HCN Channels in Inhibitory But Not Excitatory Synaptic Integration in Neurons of the Subthalamic Nucleus

The activity patterns of subthalamic nucleus (STN) neurons are intimately linked to motor function and dysfunction and arise through the complex interaction of intrinsic properties and inhibitory and excitatory synaptic inputs. In many neurons, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play key roles in intrinsic excitability and synaptic integration both under normal conditions and in disease states. However, in STN neurons, which strongly express HCN channels, their roles remain relatively obscure. To address this deficit, complementary molecular and cellular electrophysiological, imaging, and computational approaches were applied to the rat STN. Molecular profiling demonstrated that individual STN neurons express mRNA encoding several HCN subunits, with HCN2 and 3 being the most abundant. Light and electron microscopic analysis showed that HCN2 subunits are strongly expressed and distributed throughout the somatodendritic plasma membrane. Voltage-, current-, and dynamic-clamp analysis, two-photon Ca2+ imaging, and computational modeling revealed that HCN channels are activated by GABAA receptor-mediated inputs and thus limit synaptic hyperpolarization and deinactivation of low-voltage-activated Ca2+ channels. Although HCN channels also limited the temporal summation of EPSPs, generated through two-photon uncaging of glutamate, this action was largely shunted by GABAergic inhibition that was necessary for HCN channel activation. Together the data demonstrate that HCN channels in STN neurons selectively counteract GABAA receptor-mediated inhibition arising from the globus pallidus and thus promote single-spike activity rather than rebound burst firing.

Variability v.s. synchronicity of neuronal activity in local cortical network models with different wiring topologies

Dynamical behavior of a biological neuronal network depends significantly on the spatial pattern of synaptic connections among neurons. While neuronal network dynamics has extensively been studied with simple wiring patterns, such as all-to-all or random synaptic connections, not much is known about the activity of networks with more complicated wiring topologies. Here, we examined how different wiring topologies may influence the response properties of neuronal networks, paying attention to irregular spike firing, which is known as a characteristic of in vivo cortical neurons, and spike synchronicity. We constructed a recurrent network model of realistic neurons and systematically rewired the recurrent synapses to change the network topology, from a localized regular and a “small-world” network topology to a distributed random network topology. Regular and small-world wiring patterns greatly increased the irregularity or the coefficient of variation (Cv) of output spike trains, whereas such an increase was small in random connectivity patterns. For given strength of recurrent synapses, the firing irregularity exhibited monotonous decreases from the regular to the random network topology. By contrast, the spike coherence between an arbitrary neuron pair exhibited a non-monotonous dependence on the topological wiring pattern. More precisely, the wiring pattern to maximize the spike coherence varied with the strength of recurrent synapses. In a certain range of the synaptic strength, the spike coherence was maximal in the small-world network topology, and the long-range connections introduced in this wiring changed the dependence of spike synchrony on the synaptic strength moderately. However, the effects of this network topology were not really special in other properties of network activity.

Time representing cortical activities: two models inspired by prefrontal persistent activity

Abstract. Timing information in the range of seconds is significantly correlated with our behavior. There is growing interest in the cognitive behaviors that rely on perception, comparison, or generation of timing. However, little is known about the neural mechanisms underlying such behaviors. Here we model two different neural mechanisms to represent timing information in the range of seconds. In one model, a recurrent network of bistable spiking neurons shows a quasistable state that is initiated by a brief input and typically lasts for a few to several seconds. The duration of this quasistable activity may be regarded as the neural representation of internal time obeying a psychophysical law of time recognition. Another model uses synfire chains to provide the timing information necessary for predicting the times of anticipated events. In this model, the neurons projected to by multiple synfire chains are conditioned to fire synchronously at the times when an external event (GO signal) is expected. The conditioning is accomplished by spike-timing-dependent plasticity. The two models are inspired by the prefrontal activities of the monkeys engaging in different timing-information-related tasks. Thus, this cortical region may provide the timing information required for organizing various behaviors.

Structure of spontaneous UP and DOWN transitions self-organizing in a cortical network model.

Synaptic plasticity is considered to play a crucial role in the experience-dependent self-organization of local cortical networks. In the absence of sensory stimuli, cerebral cortex exhibits spontaneous membrane potential transitions between an UP and a DOWN state. To reveal how cortical networks develop spontaneous activity, or conversely, how spontaneous activity structures cortical networks, we analyze the self-organization of a recurrent network model of excitatory and inhibitory neurons, which is realistic enough to replicate UP–DOWN states, with spike-timing-dependent plasticity (STDP). The individual neurons in the self-organized network exhibit a variety of temporal patterns in the two-state transitions. In addition, the model develops a feed-forward network-like structure that produces a diverse repertoire of precise sequences of the UP state. Our model shows that the self-organized activity well resembles the spontaneous activity of cortical networks if STDP is accompanied by the pruning of weak synapses. These results suggest that the two-state membrane potential transitions play an active role in structuring local cortical circuits.

Self-organization of memory activity through spike-timing-dependent plasticity.

We studied the self-organization of memory-related activity through spike-timing-dependent plasticity (STDP). Relatively short time windows (∼10 ms) for the plasticity rule give rise to asynchronous persistent activity of low rates (20–30 Hz), which is typically observed in delay periods of working memory task. We demonstrate some network level effects on the activity regulation that cannot be addressed in single-neuron studies. For longer time windows (∼20 ms), the layered cell assemblies that propagate synchronized spikes (synfire chain) are self-organized. Synchronous spike propagation was suggested to underlie the precisely timed spikes in the monkey prefrontal cortex. The present results suggest that the two networks for sustained activity are different realizations of the same principle for synaptic wiring.

Retrieval dynamics of neural networks for sparsely coded sequential patterns

It is well known that a sparsely coded network in which the activity level is extremely low has intriguing equilibrium properties. In this work, we study the dynamical properties of a neural network designed to store sparsely coded sequential patterns rather than static ones. Applying the theory of statistical neurodynamics, we derive the dynamical equations governing the retrieval process which are described by some macroscopic order parameters such as the overlap. It is found that our theory provides good predictions for the storage capacity and the basin of attraction obtained through numerical simulations. The results indicate that the nature of the basin of attraction depends on the methods of activity control employed. Furthermore, it is found that robustness against random synaptic dilution slightly deteriorates with the degree of sparseness.

Retrieval dynamics in oscillator neural networks

We present an analytical approach that allows us to treat the long-time behavior of the recalling process in an oscillator neural network. It is well known that in coupled oscillatory neuronal systems, under suitable conditions, the original dynamics can be reduced to a simpler phase dynamics. In this description, the phases of the oscillators can be regarded as the timings of the neuronal spikes. To attempt an analytical treatment of the recalling dynamics of such a system, we study a simplified model in which we discretize time and assume a synchronous updating rule. The theoretical results show that the retrieval dynamics is described by recursion equations for some macroscopic parameters, such as an overlap with the retrieval pattern. We then treat the noise components in the local field, which arise from the learning of the unretrieved patterns, as gaussian variables. However, we take account of the temporal correlation between these noise components at different times. In particular, we find that this correlation is essential for correctly predicting the behavior of the retrieval process in the case of autoassociative memory. From the derived equations, the maximal storage capacity and the basin of attraction are calculated and graphically displayed. We also consider the more general case that the network retrieves an ordered sequence of phase patterns. In both cases, the basin of attraction remains sufficiently wide to recall the memorized pattern from a noisy one, even near saturation. The validity of these theoretical results is supported by numerical simulations. We believe that this model serves as a convenient starting point for the theoretical study of retrieval dynamics in general oscillatory systems.

Impact of network topology on inference of synaptic connectivity from multi-neuronal spike data simulated by a large-scale cortical network model

Many mechanisms of neural processing rely critically upon the synaptic connectivity between neurons. As our ability to simultaneously record from large populations of neurons expands, the ability to infer network connectivity from this data has become a major goal of computational neuroscience. To address this issue, we employed several different methods to infer synaptic connections from simulated spike data from a realistic local cortical network model. This approach allowed us to directly compare the accuracy of different methods in predicting synaptic connectivity. We compared the performance of model-free (coherence measure and transfer entropy) and model-based (coupled escape rate model) methods of connectivity inference, applying those methods to the simulated spike data from the model networks with different network topologies. Our results indicate that the accuracy of the inferred connectivity was higher for highly clustered, near regular, or small-world networks, while accuracy was lower for random networks, irrespective of which analysis method was employed. Among the employed methods, the model-based method performed best. This model performed with higher accuracy, was less sensitive to threshold changes, and required less data to make an accurate assessment of connectivity. Given that cortical connectivity tends to be highly clustered, our results outline a powerful analytical tool for inferring local synaptic connectivity from observations of spontaneous activity.

Sustained activity with low firing rate in a recurrent network regulated by spike-timing-dependent plasticity

Abstract In order to study roles of spike-timing-dependent plasticity (STDP) at the network level, we applied STDP to a model of the cortical recurrent network. We found that STDP brought self-organization of a bistable neural activity that is essential for the working memory function. Furthermore, our simulations showed that the typical two firing patterns during the persistent activity were achieved, which depend on the time window of STDP; the short time window ( ∼10 ms ) yielded an asynchronous firing activity, whereas the longer one ( ⩾20 ms ) produced a synchronous spike packet propagating along a chain of cell assemblies.

Influences of membrane properties on phase response curve and synchronization stability in a model globus pallidus neuron

The activity patterns of the globus pallidus (GPe) and subthalamic nucleus (STN) are closely associated with motor function and dysfunction in the basal ganglia. In the pathological state caused by dopamine depletion, the STN–GPe network exhibits rhythmic synchronous activity accompanied by rebound bursts in the STN. Therefore, the mechanism of activity transition is a key to understand basal ganglia functions. As synchronization in GPe neurons could induce pathological STN rebound bursts, it is important to study how synchrony is generated in the GPe. To clarify this issue, we applied the phase-reduction technique to a conductance-based GPe neuronal model in order to derive the phase response curve (PRC) and interaction function between coupled GPe neurons. Using the PRC and interaction function, we studied how the steady-state activity of the GPe network depends on intrinsic membrane properties, varying ionic conductances on the membrane. We noted that a change in persistent sodium current, fast delayed rectifier Kv3 potassium current, M-type potassium current and small conductance calcium-dependent potassium current influenced the PRC shape and the steady state. The effect of those currents on the PRC shape could be attributed to extension of the firing period and reduction of the phase response immediately after an action potential. In particular, the slow potassium current arising from the M-type potassium and the SK current was responsible for the reduction of the phase response. These results suggest that the membrane property modulation controls synchronization/asynchronization in the GPe and the pathological pattern of STN–GPe activity.