Yasuo Kawaguchi

The Graduate University for Advanced Studies | SOKENDAI

Dysfunctional dopamine signaling is implicated in various neuropsychological disorders. Previously, we reported that dopamine increases D1 receptor (D1R)-expressing medium spiny neuron (MSN) excitability and firing rates in the nucleus accumbens (NAc) via the PKA/Rap1/ERK pathway to promote reward behavior. Here, the results show that the D1R agoni...

In mammalian neocortex, learning triggers the formation and turnover of new postsynaptic spines on pyramidal cell dendrites. However, the biological principles of spine reorganization during learning remain elusive because the identity of their presynaptic neuronal partners is unknown. Here, we show that two presynaptic neural circuits supervise di...

Feedback projections from the secondary motor cortex (M2) to the primary motor and sensory cortices are essential for behavior selection and sensory perception. Intratelencephalic (IT) cells in layer 5 (L5) contribute feedback projections to diverse cortical areas. Here we show that L5 IT cells participating in feedback connections to layer 1 (L1)...

The cortex processes information through intricate circuitry and outputs to multiple brain areas by different sets of pyramidal cells (PCs). PCs form intra- and inter-laminar subnetworks, depending on PC projection subtypes. However, it remains unknown how individual PC subtypes are involved in cortical network activity and, thereby, in distinct br...

Dopamine plays a key role in the modulation of the circuit activity in striatum for reward behavior. We have reported that dopamine type 1 receptor (D1R) signaling in the striatum presumably regulates neuronal excitability and reward-related behaviors through PKA/Rap1/MAPK pathway. However, how D1Rs and its downstream signaling regulate neuronal ex...

There exist two major types of striatum-targeting neocortical neurons, specifically, intratelencephalic (IT) neurons and pyramidal-tract (PT) neurons. Regarding their striatal projections, it was once suggested that IT axons are extended whereas PT axons are primarily focal. However, subsequent study with an increased number of well-stained extende...

There exist two major types of striatum-targeting neocortical neurons, specifically, intratelencephalic (IT) neurons and pyramidal-tract (PT) neurons. Regarding their striatal projections, it was once suggested that IT axons are extended whereas PT axons are primarily focal. However, subsequent study with an increased number of well-stained extende...

In the neocortex, both layer 2/3 and layer 5 contain corticocortical pyramidal cells projecting to other cortices. We previously found that, among L5 pyramidal cells of the secondary motor cortex (M2), not only intratelencephalic projection cells but also pyramidal tract cells innervate ipsilateral cortices, and that the two subtypes are different...

The cortex contains multiple neuron types with specific connectivity and functions. Recent progress has provided a better understanding of the interactions of these neuron types as well as their output organization particularly for the frontal cortex, with implications for the circuit mechanisms underlying cortical oscillations that have cognitive...

The hypothesis that the basal-ganglia direct and indirect pathways represent goodness (or benefit) and badness (or cost) of options, respectively, explains a wide range of phenomena. However, this hypothesis, named the Opponent Actor Learning (OpAL), still has limitations. Structurally, the OpAL model does not incorporate differentiation of the two...

After brain injury, neural stem cell–derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast migration is res...

One recent technical innovation in neuroscience is microcircuit analysis using three-dimensional reconstructions of neural elements with a large volume Electron microscopy (EM) data set. Large-scale data sets are acquired with newly-developed electron microscope systems such as automated tape-collecting ultramicrotomy (ATUM) with scanning EM (SEM),...

The hypothesis that the basal-ganglia direct and indirect pathways represent goodness (or benefit) and badness (or cost) of options, respectively, explains a wide range of phenomena. However, this hypothesis, named the Opponent Actor Learning (OpAL), still has limitations. Structurally, the OpAL model does not incorporate differentiation of the two...

The basal ganglia play key roles in adaptive behaviors guided by reward and punishment. However, despite accumulating knowledge, few studies have tested how heterogeneous signals in the basal ganglia are organized and coordinated for goal-directed behavior. In this study, we investigated neuronal signals of the direct and indirect pathways of the b...

The thalamus is the hub through which neural signals are transmitted from the basal ganglia and cerebellum to the neocortex. However, thalamocortical axonal activity during motor learning remains largely undescribed. We conducted two-photon calcium imaging of thalamocortical axonal activity in the motor cortex of mice learning a self-initiated leve...

Automated tape-collecting ultramicrotomy in conjunction with scanning electron microscopy (SEM) is a powerful approach for volume electron microscopy and three-dimensional neuronal circuit analysis. Current tapes are limited by section wrinkle formation, surface scratches and sample charging during imaging. Here we show that a plasma-hydrophilized...

A prominent feature of neocortical pyramidal cells (PCs) is their numerous projections to diverse brain areas. In layer 5 (L5) of the rat frontal cortex, there are 2 major subtypes of PCs that differ in their long-range axonal projections, corticopontine (CPn) cells and crossed corticostriatal (CCS) cells. The outputs of these L5 PCs can be regulat...

The frontal cortical areas make a coordinated response that generates appropriate behavior commands, using individual local circuits with corticostriatal and corticocortical connections in longer time scales than sensory areas. In secondary motor cortex (M2), situated between the prefrontal and primary motor areas, major subtypes of layer 5 cortico...

Jiang et al. (Research Article, 27 November 2015, aac9462) describe detailed experiments that substantially add to the knowledge of cortical microcircuitry and are unique in the number of connections reported and the quality of interneuron reconstruction. The work appeals to experts and laypersons because of the notion that it unveils new principle...

The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitor...

Unlabelled: Slow-wave oscillations, the predominant brain rhythm during sleep, are composed of Up/Down cycles. Depolarizing Up-states involve activity in layer 5 (L5) of the neocortex, but it is unknown how diverse subtypes of neurons within L5 participate in generating and maintaining Up-states. Here we compare the in vivo firing patterns of cort...

There are two prevailing notions regarding the involvement of the cortico-basal ganglia system in value-based learning: (1) the direct and indirect pathways of the basal ganglia are crucial for appetitive and aversive learning, respectively, and (2) the activity of midbrain dopamine neurons represents reward-prediction-error. While (2) constitutes...

Most glutamatergic inputs in the neocortex originate from the thalamus or neocortical pyramidal cells. To test whether thalamocortical afferents selectively innervate specific cortical cell subtypes and surface domains, we investigated the distribution patterns of thalamocortical and corticocortical excitatory synaptic inputs in identified postsyna...

Excitatory cortical neurons project to various subcortical and intracortical regions, and exhibit diversity in their axonal connections. Although this diversity may develop from primary axons, how many types of axons initially occur remains unknown. Using a sparse-labeling in utero electroporation method, we investigated the axonal outgrowth of the...

The frontal cortex plays an important role in the initiation and execution of movements via widespread projections to various cortical and subcortical areas. Layer 2/3 (L2/3) pyramidal cells in the frontal cortex send axons mainly to other ipsilateral/contralateral cortical areas. Subpopulations of layer 5 (L5) pyramidal cells that selectively proj...

The neocortex consists of many diverse neuron populations distributed across cortical layers having specialized connectivity and projection patterns. Glutamatergic pyramidal cells, which are cortical projection neurons, reside in all layers except layer 1, while GABAergic nonpyramidal cells are ubiquitous throughout all cortical layers. These broad...

Cortical fast-spiking (FS) interneurons are electrically interconnected through gap junctions and form dendritic net structures extending over different functional columns. Here, we investigated how pyramidal cells regulate FS cell network activity. Using paired recordings and glutamate puff-stimulations, we found that FS cell pairs connected by el...

Humans and animals take actions quickly when they expect that the actions lead to reward, reflecting their motivation. Injection of dopamine receptor antagonists into the striatum has been shown to slow such reward-seeking behavior, suggesting that dopamine is involved in the control of motivational processes. Meanwhile, neurophysiological studies...

Higher-order motor cortices, such as the secondary motor area (M2) in rodents, select future action patterns and transmit them to the primary motor cortex (M1). To better understand motor processing, we characterized "top-down" and "bottom-up" connectivities between M1 and M2 in the rat cortex. Somata of pyramidal cells (PCs) in M2 projecting to M1...

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using...

Neurons receive thousands of synaptic inputs onto their dendrites and soma, and spatially and temporally integrate these inputs to produce appropriate output in the form of action potentials generated in axons. The morphology of dendrites can influence the integration of synaptic input, as well as affect the pattern of action potentials. Using comp...

Midbrain dopamine neurons supposedly encode reward prediction error, but how error signals are computed remains elusive. Here, we propose a mechanism based on recent findings regarding corticostriatal circuits. Specifically, we propose that two distinct subpopulations of corticostriatal neurons differentially represent the animal's current and prev...

During sleep, the electroencephalogram exhibits synchronized slow waves that desynchronize when animals awaken [desynchronized states (DSs)]. During slow-wave states, the membrane potentials of cortical neurons oscillate between discrete depolarized states ("Up states") and periods of hyperpolarization ("Down states"). To determine the role of cort...

How information is manipulated and segregated within local circuits in the frontal cortex remains mysterious, in part because of inadequate knowledge regarding the connectivity of diverse pyramidal cell subtypes. The frontal cortex participates in the formation and retrieval of declarative memories through projections to the perirhinal cortex, and...

Since late 1980s, the whole-cell patch-clamp technique has been used as a powerful tool for analyzing local circuits of the central nervous system in a brain slice preparation in which the fundamental architecture of local circuits is mostly maintained. When combined with intracellular staining techniques, the technique allows high-resolution analy...

The identification and characterization of excitatory and inhibitory neurons are significant steps in understanding neural network functions. In this study, we investigated the intrinsic electrophysiological properties of neurons in the prepositus hypoglossi nucleus (PHN), a brainstem structure that is involved in gaze holding, using whole-cell rec...

Dendritic trees influence synaptic integration and neuronal excitability, yet appear to develop in rather arbitrary patterns. Using electron microscopy and serial reconstructions, we analyzed the dendritic trees of four morphologically distinct neocortical interneuron subtypes to reveal two underlying organizational principles common to all. First,...

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Most glutamatergic inputs in the neocortex originate from the thalamus or neocortical pyramidal cells. To test whether thalamocortical afferents selectively innervate specific cortical cell subtypes and surface domains, we investigated the distribution patterns of thalamocortical and corticocortical excitatory synaptic inputs in identified postsyna...

Whether neocortical γ-aminobutyric acid (GABA) cells are composed of a limited number of distinct classes of neuron, or whether they are continuously differentiated with much higher diversity, remains a contentious issue for the field. Most GABA cells of rat frontal cortex have at least 1 of 6 chemical markers (parvalbumin, calretinin, alpha-actini...

Pyramidal cells in the neocortex are differentiated into several subgroups based on their extracortical projection targets. However, little is known regarding the relative intracortical connectivity of pyramidal neurons specialized for these specific output channels. We used paired recordings and quantitative morphological analysis to reveal distin...

Recent advances have established that intralaminar and interlaminar excitatory networks between neocortical pyramidal cells are specialized into subnetworks. Here, we have investigated how the commissural system organizes the intracortical excitatory subnetworks to communicate between cortical hemispheres. Whole-cell recordings were obtained from c...

Alterations of the serotonergic system in the prefrontal cortex (PFC) are implicated in psychiatric disorders such as schizophrenia and depression. Although abnormal synchronous activity is observed in the PFC of these patients, little is known about the role of serotonin (5-HT) in cortical synchrony. We found that 5-HT, released by electrical stim...

Alterations of the serotonergic system in the prefrontal cortex (PFC) are implicated in psychiatric disorders such as schizophrenia and depression. Although abnormal synchronous activity is observed in the PFC of these patients, little is known about the role of serotonin (5-HT) in cortical synchrony. We found that 5-HT, released by electrical stim...

To understand the structural and functional principles of the neocortex it is essential to identify the functional classes of cortical neurons and their patterns of synaptic connectivity. Neocortical neurons can be divided into two generalized types, excitatory pyramidal cells utilizing glutamate as a transmitter, and nonpyramidal cells that genera...

The neocortical circuit is composed of excitatory principal neurons and inhibitory interneurons. Recent advances have established that multiple subnetworks of synaptically coupled excitatory neurons provide distinct pathways for information flow through the cortical circuit. Here we have investigated how inhibitory interneurons are incorporated int...