Ryuichi Nakajima

Nagoya University | Meidai · Academic Research & Industry-Academia-Government Collaboration

Numerous pathogenic variants of SCN2A gene, encoding voltage-gated sodium channel α2 subunit Nav1.2 protein, have been identified in a wide spectrum of neuropsychiatric disorders including schizophrenia. However, pathological mechanisms for the schizophrenia-relevant behavioral abnormalities caused by the variants remain poorly understood. Here in...

The dentate gyrus (DG) plays critical roles in cognitive functions, such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca ²⁺ imaging in freely movi...

Aim Experimental animals, such as non-human primates (NHPs), mice, Zebrafish, and Drosophila, are frequently employed as models to gain insights into human physiology and pathology. In developmental neuroscience and related research fields, information about the similarities of developmental gene expression patterns between animal models and humans...

The CA1 area in the mammalian hippocampus is essential for spatial learning. Pyramidal cells are the hippocampus output neurons and their activities are regulated by inhibition exerted by a diversified population of interneurons. Lateral inhibition has been suggested as the mechanism enabling the reconfiguration of pyramidal cell assembly activity...

Aims Neurogranin (NRGN) is a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. Recent studies suggest that NRGN is involved in neuropsychiatric disorders, including schizophrenia, ADHD, and Alzheimer's disease. Previous behavioral studies of Nrgn knockout (Nrgn KO) mice identified hyperactivity, deficits in spat...

The dentate gyrus (DG) plays critical roles in cognitive functions such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca2+ imaging in freely moving...

The dentate gyrus (DG) plays critical roles in cognitive functions such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca ²⁺ imaging in freely movin...

The dentate gyrus (DG) plays critical roles in cognitive functions such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca2+ imaging in freely moving...

Aims: Synaptic Ras GTPase-activating protein 1 (SYNGAP1) regulates synaptic plasticity through AMPA receptor trafficking. SYNGAP1 mutations have been found in human patients with intellectual disability (ID) and autism spectrum disorder (ASD). Almost every individual with SYNGAP1-related ID develops epilepsy, and approximately 50% have ASD. SYNGAP...

Significance Impulsivity is a tendency to act with little or no forethought or consideration of the consequences and is a major component of various psychiatric disorders. However, little is known about the brain circuits that regulate reward-related impulsivity. Our genetic manipulations reveal that dopamine D2 receptors in the central nucleus of...

To understand the circuitry of the brain, it is essential to clarify the functional connectivity among distinct neuronal populations. For this purpose, neuronal activity imaging using genetically-encoded calcium sensors such as GCaMP has been a powerful approach due to its cell-type specificity. However, calcium (Ca²⁺) is an indirect measure of neu...

An improved genetically encoded voltage indicator (GEVI) was achieved by altering the charge composition of the region linking the voltage-sensing domain of the GEVI to a pH-sensitive fluorescent protein. Negatively charged linker segments reduced the voltage-dependent optical signal while positively charged linkers increased the signal size. Argin...

Basal ganglia (BG) circuits orchestrate complex motor behaviors predominantly via inhibitory synaptic outputs. Although these inhibitory BG outputs are known to reduce the excitability of postsynaptic target neurons, precisely how this change impairs motor performance remains poorly understood. Here, we show that optogenetic photostimulation of inh...

The age of genetically encoded voltage indicators has matured to the point that changes in membrane potential can now be observed optically in vivo. Improving the signal size and speed of these voltage sensors has been the primary driving forces during this maturation process. As a result, there is a wide range of probes using different voltage det...

Light-activated ion channels and pumps can be employed as optogenetic actuators to control the electrical activity of neurons and other excitable cells. A variety of optogenetic actuators are available that allow light to either turn on electrical activity (photostimulate) or turn off electrical activity (photoinhibit). Because of their genetic tar...

In Pavlovian fear conditioning, the lateral amygdala (LA) has been highlighted as a key brain site for association between sensory cues and aversive stimuli. However, learning-related changes are also found in upstream sensory regions such as thalamus and cortex. To isolate the essential neural circuit components for fear memory association, we tes...

Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. These mice permit photoinhibition or photostimulation both in vitro a...

Scanning small spots of laser light allows mapping of synaptic circuits in brain slices from transgenic mice expressing channelrhodopsin-2 (ChR2). These light spots photostimulate presynaptic neurons expressing ChR2, while postsynaptic responses can be monitored in neurons that do not express ChR2. Correlating the location of the light spot with th...

The lateral amygdala (LA) has been proposed as a critical site of memory storage during auditory fear conditioning, with long-term potentiation (LTP) of LA synapses suggested to be the cellular mechanism underlying fear memory formation. However, similar synaptic changes are also observed in upstream areas, such as the medial geniculate nucleus (MG...

Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated catio...

Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-k...

Crawley's Sociability and social novelty preference test. We could not detect any significant difference between genotypes in exploratory behavior within either the first trial with one stranger mouse (F1,34 = 1.496, P = 0.2297 in the empty side; F1,34 = 0.242, P = 0.6256 in the stranger side; A), nor the following trial with an additional stranger...

Social interaction in home cage. Social interactions in home cage were normal in clustering (F1,17 = 0.54, P = 0.820; A). Activity level was not significantly different between genotypes either (F1,17 = 0.38, P = 0.547; B).

Comparison of mRNA expression levels of μ-calpain, m-calpain and calpastatin. Using Allen Brain Atlas, an in situ hybridization database of mouse brain, mRNA expression levels were compared among μ-calpain, m-calpain and calpastatin (Arranged to a bar chart by authors). Allen Brain Atlas [Internet]. Seattle (WA): Allen Institute for Brain Science....

Light and dark transition test. CS-KO mice showed no significant differences in the light/dark transition test in distance traveled (F1,36 = 0.011, P = 0.917 in light camber, F1,36 = 0.293, P = 0.592 in the dark chamber; Aa), in stay time in the light chamber (F1,36 = 0.158, P = 0.694; Ab), in the number of transitions (F1,36 = 0.448, P = 0.508; Ac...

A subtle but chronic alteration in metabolic balance between amyloid-β peptide (Aβ) anabolic and catabolic activities is thought to cause Aβ accumulation, leading to a decade-long pathological cascade of Alzheimer disease. However, it is still unclear whether a reduction of the catabolic activity of Aβ in the brain causes neuronal dysfunction in vi...

Although mannitol has been used as an osmotherapeutic drug on brain injury, the clinical efficiency of the drug are still controversial. In the present study, we examined the effects of mannitol on the edema in a hippocampal slice due to brief ischemia. To evaluate the effects, we employed an image analysis system that consists of an infrared-diffe...

We have developed a novel device for the quantification of swelling of cells in acute brain slices. We can also carry out detailed real-time monitoring of hippocampal cells. The device we developed is based on an infrared differential interference contrast microscopy (IR-DIC) and a custom-made real-time computerized image analysis system for the qu...

We have developed a novel device for the quantification of edematous morphology changes in acute brain slices. We can also carry out real-time monitoring of detailed hippocampal cells. The device we developed is based on infrared differential interference contrast microscopy (IR-DIC) and a custom-made real-time computerized image-analysis system fo...