Gen Ohtsuki

Cerebellar dysfunction relates to various psychiatric disorders, including autism spectrum and depressive disorders. However, the physiological aspect is less advanced. Here, we investigate the immune-triggered hyperexcitability in the cerebellum on a wider scope. Activated microglia via exposure to bacterial endotoxin lipopolysaccharide or heat-killed Gram-negative bacteria induce a potentiation of the intrinsic excitability in Purkinje neurons, which is suppressed by microglia-activity inhibit

The physiology of climbing fiber signals in cerebellar Purkinje cells has been studied since the early days of electrophysiology. Both the climbing fiber-evoked complex spike and the role of climbing fiber activity in the induction of long-term depression (LTD) at parallel fiber-Purkinje cell synapses have become hallmark features of cerebellar physiology. However, the key role of climbing fiber signaling in cerebellar motor learning has been challenged by recent reports of forms of synaptic and

Climbing fibers provide one of the two major excitatory inputs to the cerebellar cortex. In an immature animal, several climbing fibers form synapses with one Purkinje neuron. During postnatal development most climbing fiber innervations with a Purkinje neuron are eliminated and only one strong fiber remains. Previous studies suggested that this pruning of surplus climbing fiber innervations depends on the neuronal activity. We hypothesized that synaptic plasticity might play a role in the matur

Neurons store information and participate in memory engrams as a result of experience-dependent changes in synaptic weights and in membrane excitability. Here, we examine excitatory postsynaptic potential (EPSP) amplitude and neuronal excitability in relation to these two mechanisms of plasticity. We analyze somato-dendritic double-patch recordings from cerebellar Purkinje cells while inducing intrinsic, SK2 channel-dependent plasticity or blocking SK channels with bath application of apamin. Bo

The cerebellum, a universal processor for sensory acquisition and internal models, and its association with synaptic and nonsynaptic plasticity have been envisioned as the biological correlates of learning, perception, and even thought. Indeed, the cerebellum is no longer considered merely as the locus of motor coordination and its learning. Here, we introduce the mechanisms underlying the induction of multiple types of plasticity in cerebellar circuit and give an overview focusing on the plasti

The cerebellum governs motor coordination and motor learning. Infection with external microorganisms, such as viruses, bacteria, and fungi, induces the release and production of inflammatory mediators, which drive acute cerebellar inflammation. The clinical observation of acute cerebellitis is associated with the emergence of cerebellar ataxia. In our animal model of the acute inflammation of the cerebellar cortex, animals did not show any ataxia but hyperexcitability in the cerebellar cortex an

A novel ionotropic glutamate receptor subunit delta2 (GluRdelta2), which is specifically expressed in cerebellar Purkinje neurons (PNs), is implicated in the induction of long-term depression. Mutant mice deficient in GluRdelta2 (delta2-/-) have abnormal cerebellar synaptic organization and impaired motor coordination and learning. Previous in vivo extracellular recordings indelta2-/- revealed that PN activity distinct from that in wild-type (WT) mice is attributable to enhanced climbing fiber a

The role of dendrites in the integration of widespread synaptic activity has been studied in experiments and theories (Johnston et al., 1996; Magee, 2007). However, whether the conduction of synaptic currents from dendrites to the soma depends on excitability of those dendritic branches is unclear. How modulation of the branch excitability affects the conduction of synaptic inputs and their selection on dendrites is also elusive. Here, I performed simultaneous voltage-clamp recordings from the s

Lipopolysaccharide (LPS), an outer component of Gram-negative bacteria, induces a strong response of innate immunity via microglia, which triggers a modulation of the intrinsic excitability of neurons. However, it is unclear whether the modulation of neurophysiological properties is similar among neurons. Here, we found the hypoexcitability of layer 5 (L5) pyramidal neurons after exposure to LPS in the medial prefrontal cortex (mPFC) of juvenile rats. We recorded the firing frequency of L5 pyram

Immune cells play numerous roles in the host defense against the invasion of microorganisms and pathogens, which induces the release of inflammatory mediators (e.g., cytokines and chemokines). In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dyna

Neuroinflammation in the brain is thought related to the emergence of various psychoses, although the identifying regional significance, the involvement of immune-cells and lymphocytic activity, and ways for the therapeutic recovery are under the effort of researchers. We recently revealed that the cerebellar acute inflammation causes the symptoms manifested in mood disorders or developmental disorders, which were associated with hyperexcitability due to immune-triggered plasticity and the overc

The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is