The origin of the spatial receptive fields hippocampal place cells has not been established. A CA1 pyramidal cell receives thousands synaptic inputs, mostly from other spatially tuned neurons; however, how postsynaptic neuron's cellular properties determine response to these inputs during behavior is unknown. We discovered that, contrary expectations basic models and neuronal integration, a small, uniform depolarization untuned somatic membrane potential silent leads sudden reversible...

Abstract Animals tend to alternate between different choices, which requires the ability remember recent choices. The Y-maze spontaneous alternation test is widely used in various animal models for assessing short-term memory, and its precise evaluation depends upon accurate determination of arm visit sequence. However, an objective method defining visits lacking owing uncertainty regarding extent must go into be considered visited. Here, we conducted quantitative analyses on mice behavior...

Abstract Recognizing an individual and retrieving updating the value information assigned to are fundamental abilities for establishing social relationships. To understand neural mechanisms underlying association between identity reward value, we developed Go-NoGo discrimination paradigms that required male subject mice distinguish familiar based on their individually unique characteristics associate them with availability. We found could discriminate conspecifics through a brief...

Achieving long-lasting neuronal modulation with low-intensity, low-frequency ultrasound is challenging. Here, we devised theta burst stimulation (TBUS) gamma bursts for brain entrainment and of plasticity in the mouse motor cortex. We demonstrate that two types TBUS, intermittent continuous induce bidirectional long-term potentiation or depression-like plasticity, respectively, as evidenced by changes motor-evoked potentials. These effects depended on molecular pathways associated including...

Previous studies indicate that boutons from the same axon exhibit distinct Ca 2+ dynamics depending on postsynaptic targets. Mossy fibers of hippocampal granule cells innervate synaptic targets via morphologically boutons. We investigated mitochondrial involvement in generation post-tetanic residual (Ca res ) at large and small en passant mossy fiber (MFBs). Mitochondria limited [Ca ] i build-up during high-frequency stimulation (HFS) MFBs, but not MFBs. The amount , quantified as a time...

Phosphatidylionsitol 4,5-bisphosphate (PIP(2)), a substrate of phospholipase C, has recently been recognized to regulate membrane-associated proteins and act as signal molecule in C-linked Gq-coupled receptor (GqPCR) pathways. However, it is not known whether PIP(2) depletion induced by GqPCRs can receptor-specific signals native cells. We investigated this issue cardiomyocytes where PIP(2)-dependent ion channels, G protein-gated inwardly rectifying K(+) (GIRK) background (IRK) various are...

We have shown previously that cardiac G protein-gated inwardly rectifying K + (GIRK) channels are inhibited by Gq protein-coupled receptors (GqPCRs) via phosphatidylinositol 4,5-bisphosphate (PIP 2 ) depletion in a receptor-specific manner. To investigate the mechanism of receptor specificity, we examined whether activation GqPCRs induces localized PIP depletion. When applied endothelin-1 to bath, GIRK channel activities recorded cell-attached patches were not changed, implying signal is...

It has been shown that the activation of G(q)-coupled receptors (G(q)PCRs) in cardiac myocytes inhibits G protein-gated inwardly rectifying K(+) current (I(GIRK)) via receptor-specific depletion phosphatidylinositol 4,5-bisphosphate (PIP(2)). In this study, we investigated mechanism receptor-mediated regulation I(GIRK) acutely isolated hippocampal CA1 neurons by muscarinic receptor agonist, carbachol (CCh), and group I metabotropic glutamate (mGluR) 3,5-dihydroxyphenylglycine (DHPG). was...

We have previously shown that K + -dependent Na /Ca 2+ exchanger (NCKX) is a major calcium clearance mechanism at the large axon terminals of central neurons, whereas their somata display little NCKX activity. investigated mechanisms underlying axonal polarization NCKX2 in rat hippocampal neurons. identified as first neuron-specific cargo molecule kinesin family member 21A (KIF21A). The intracellular loop specifically interacted with WD-40 repeats, putative cargo-binding domain, KIF21A....

Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs mGluRs, respectively). The two types of interact with each other, as exemplified by modulation iGluRs mGluRs. However, other way interaction (i.e., mGluRs iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is sufficient to activate phospholipase C (PLC) rat hippocampus, while robustly...

Abstract Strong hippocampal mossy fiber synapses are thought to function as detonators, imposing “teaching” signals onto CA3 neurons during new memory formation. For an empirical test of this long‐standing view, we examined effects optogenetically stimulating fibers on spatial firing in freely‐moving mice. We found that spatially restricted stimulation drives novel place‐specific some pyramidal neurons. Such comprise only a minority, however, and many more showed inhibited stimulation. Also,...

Social and reward signal processing their association are critical elements of social motivation. Despite the use learning to improve interactions patients with autism spectrum disorder (ASD), underlying neural mechanisms unknown. Here, we found different yet conjunct neuronal representations signals in mouse medial prefrontal cortex (mPFC). We also that is selectively disrupted, whereas intact mPFC Shank2-knockout mice, a model ASD. Furthermore, not only allows mice associate stimuli...

Abstract Neural network activity regulates the development of hippocampal newborn granule cells (GCs). Excitatory GABAergic input is known to be a key player in this regulation. Although calcium signaling thought downstream mediator GABA, GABA‐induced GCs not well understood. We investigated Ca 2+ and its regulatory role axon dendrite outgrowth identified organotypic slice culture early postnatal rat hippocampus. Here, we report that can induce transients (CaTs) during first post‐mitotic...

Group I metabotropic glutamate receptors (group mGluRs; mGluR1 and mGluR5) exert diverse effects on neuronal synaptic functions, many of which are regulated by intracellular Ca2+. In this study, we characterized the cellular mechanisms underlying Ca2+ mobilization induced (RS)-3,5-dihydroxyphenylglycine (DHPG; a specific group mGluR agonist) in somata acutely dissociated rat hippocampal neurons using microfluorometry. We found that DHPG activates mGluR5 to mobilize from ryanodine-sensitive...

Abstract: We investigated Ca 2+ clearance mechanisms (CCMs) at the axon terminals of mammalian central neurons: neurohypophysial (NHP) and calyces Held. transients were evoked by applying a short depolarization pulse via patch pipette containing indicator dye. Quantitative analysis decay phases revealed that Na + /Ca exchange (Na/CaX) is major CCM both terminals. In contrast, no Na/CaX activity was found in somata NHP (supraoptic magnocellular neurons), indicating distribution exchangers...

Whole-cell recording has been used to measure and manipulate a neuron's spiking subthreshold membrane potential, allowing assessment of the cell's inputs outputs as well its intrinsic properties. This technique also combined with pharmacology optogenetics morphological reconstruction address critical questions concerning neuronal integration, plasticity, connectivity. protocol describes for obtaining whole-cell recordings in awake head-fixed animals, such be investigated within context an...

Intracellular recording is an essential technique for investigating cellular mechanisms underlying complex brain functions. Despite the high sensitivity of to mechanical disturbances, intracellular has been applied awake, behaving, and even freely moving, animals. Here we summarize recent advances in these methods their application measurement manipulation membrane potential dynamics understanding neuronal computations behaving

Whole-cell recording is a key technique for investigating synaptic and cellular mechanisms underlying various brain functions. However, because of its high sensitivity to mechanical disturbances, applying the whole-cell method freely moving animals has been challenging. Here, we describe obtaining such recordings in moving, drug-free with success rate. This involves three major steps: from awake head-fixed animals, reliable efficient stabilization pipette respect animal’s head using an...

Abstract Episodic memories are initially encoded in the hippocampus and subsequently undergo systems consolidation into neocortex. The nature of memory stored neocortex also differs, with cortex shown to encode more generalized forms. Although several brain regions known social information, specific cortical circuits involved information remain unclear. Using vivo Ca 2+ imaging optogenetic manipulations, we found that infralimbic (IL) neurons projecting nucleus accumbens shell (IL →NAcSh )...

Abstract Hippocampal mossy fibers have long been proposed to impose new patterns learn onto CA3 neurons during memory formation. However, inconsistent with this theory, we found in our previous study that fiber stimulation induces only transient changes spatial firing a familiar environment. Here, tested whether affects differently between and novel environments. We compared of before after optogenetic freely behaving mice three sets are more responsive the than failed obtain evidence for...

Abstract Strong hippocampal mossy fiber synapses are thought to function as detonators, imposing ‘teaching’ signals onto CA3 neurons during new memory formation. For an empirical test of this long-standing view, we examined effects stimulating fibers on spatial firing in freely-moving mice. We found that optogenetic stimulation can alter firing, but their only transient. Spatially restricted stimulation, either congruent or incongruent with place fields, was more likely suppress than enhance...