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Find video protocols related to scientific articles indexed in Pubmed.
Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes.
Nat. Biotechnol.
PUBLISHED: 04-10-2014
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Specification of cell identity during development depends on exposure of cells to sequences of extrinsic cues delivered at precise times and concentrations. Identification of combinations of patterning molecules that control cell fate is essential for the effective use of human pluripotent stem cells (hPSCs) for basic and translational studies. Here we describe a scalable, automated approach to systematically test the combinatorial actions of small molecules for the targeted differentiation of hPSCs. Applied to the generation of neuronal subtypes, this analysis revealed an unappreciated role for canonical Wnt signaling in specifying motor neuron diversity from hPSCs and allowed us to define rapid (14 days), efficient procedures to generate spinal and cranial motor neurons as well as spinal interneurons and sensory neurons. Our systematic approach to improving hPSC-targeted differentiation should facilitate disease modeling studies and drug screening assays.
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Modulating excitation through plasticity at inhibitory synapses.
Front Cell Neurosci
PUBLISHED: 01-01-2014
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Learning is believed to depend on lasting changes in synaptic efficacy such as long-term potentiation and long-term depression. As a result, a profusion of studies has tried to elucidate the mechanisms underlying these forms of plasticity. Traditionally, experience-dependent changes at excitatory synapses were assumed to underlie learning and memory formation. However, with the relatively more recent investigation of inhibitory transmission, it had become evident that inhibitory synapses are not only plastic, but also provide an additional way to modulate excitatory transmission and the induction of plasticity at excitatory synapses. Thanks to recent technological advances, progress has been made in understanding synaptic transmission and plasticity from particular interneuron subtypes. In this review article, we will describe various forms of synaptic plasticity that have been ascribed to two fairly well characterized populations of interneurons in the hippocampus, those expressing cholecystokinin (CCK) and parvalbumin (PV). We will discuss the resulting changes in the strength and plasticity of excitatory transmission that occur in the local circuit as a result of the modulation of inhibitory transmission. We will focus on the hippocampus because this region has a relatively well-understood circuitry, numerous forms of activity-dependent plasticity and a multitude of identified interneuron subclasses.
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Delta-opioid receptors mediate unique plasticity onto parvalbumin-expressing interneurons in area CA2 of the hippocampus.
J. Neurosci.
PUBLISHED: 09-06-2013
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Inhibition is critical for controlling information transfer in the brain. However, the understanding of the plasticity and particular function of different interneuron subtypes is just emerging. Using acute hippocampal slices prepared from adult mice, we report that in area CA2 of the hippocampus, a powerful inhibitory transmission is acting as a gate to prevent CA3 inputs from driving CA2 neurons. Furthermore, this inhibition is highly plastic, and undergoes a long-term depression following high-frequency 10 Hz or theta-burst induction protocols. We describe a novel form of long-term depression at parvalbumin-expressing (PV+) interneuron synapses that is dependent on delta-opioid receptor (DOR) activation. Additionally, PV+ interneuron transmission is persistently depressed by DOR activation in area CA2 but only transiently depressed in area CA1. These results provide evidence for a differential temporal modulation of PV+ synapses between two adjacent cortical circuits, and highlight a new function of PV+ cells in controlling information transfer.
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CA1 pyramidal cell theta-burst firing triggers endocannabinoid-mediated long-term depression at both somatic and dendritic inhibitory synapses.
J. Neurosci.
PUBLISHED: 08-23-2013
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Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner.
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Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage.
Cell
PUBLISHED: 09-26-2011
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The cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a regulator of local protein synthesis, is the mouse homolog of ApCPEB, a functional prion protein in Aplysia. Here, we provide evidence that CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase. In hippocampal cultures, CPEB3 activated by Neuralized1-mediated ubiquitination leads both to the growth of new dendritic spines and to an increase of the GluA1 and GluA2 subunits of AMPA receptors, two CPEB3 targets essential for synaptic plasticity. Conditional overexpression of Neuralized1 similarly increases GluA1 and GluA2 and the number of spines and functional synapses in the hippocampus and is reflected in enhanced hippocampal-dependent memory and synaptic plasticity. By contrast, inhibition of Neuralized1 reduces GluA1 and GluA2 levels and impairs hippocampal-dependent memory and synaptic plasticity. These results suggest a model whereby Neuralized1-dependent ubiquitination facilitates hippocampal plasticity and hippocampal-dependent memory storage by modulating the activity of CPEB3 and CPEB3-dependent protein synthesis and synapse formation.
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Synaptic integration by different dendritic compartments of hippocampal CA1 and CA2 pyramidal neurons.
Cell. Mol. Life Sci.
PUBLISHED: 03-18-2011
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Pyramidal neurons have a complex dendritic arbor containing tens of thousands of synapses. In order for the somatic/axonal membrane potential to reach action potential threshold, concurrent activation of multiple excitatory synapses is required. Frequently, instead of a simple algebraic summation of synaptic potentials in the soma, different dendritic compartments contribute to the integration of multiple inputs, thus endowing the neuron with a powerful computational ability. Most pyramidal neurons share common functional properties. However, different and sometimes contrasting dendritic integration rules are also observed. In this review, we focus on the dendritic integration of two neighboring pyramidal neurons in the hippocampus: the well-characterized CA1 and the much less understood CA2. The available data reveal that the dendritic integration of these neurons is markedly different even though they are targeted by common inputs at similar locations along their dendrites. This contrasting dendritic integration results in different routing of information flow and generates different corticohippocampal loops.
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Strong CA2 pyramidal neuron synapses define a powerful disynaptic cortico-hippocampal loop.
Neuron
PUBLISHED: 04-09-2010
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Neurons propagate information through circuits by integrating thousands of synaptic inputs to generate an action potential output. Inputs from different origins are often targeted to distinct regions of a neurons dendritic tree, with synapses on more distal dendrites normally having a weaker influence on cellular output compared to synapses on more proximal dendrites. Here, we report that hippocampal CA2 pyramidal neurons, whose function has remained obscure for 75 years, have a reversed synaptic strength rule. Thus, CA2 neurons are strongly excited by their distal dendritic inputs from entorhinal cortex but only weakly activated by their more proximal dendritic inputs from hippocampal CA3 neurons. CA2 neurons in turn make strong excitatory synaptic contacts with CA1 neurons. In this manner, CA2 neurons form the nexus of a highly plastic disynaptic circuit linking the cortical input to the hippocampus to its CA1 neuronal output. This circuit is likely to mediate key aspects of hippocampal-dependent spatial memory.
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Estradiol rescues neurons from global ischemia-induced cell death: multiple cellular pathways of neuroprotection.
Steroids
PUBLISHED: 01-08-2009
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The potential neuroprotective role of sex hormones in chronic neurodegenerative disorders and acute brain ischemia following cardiac arrest and stroke is of a great therapeutic interest. Long-term pretreatment with estradiol and other estrogens affords robust neuroprotection in male and female rodents subjected to focal and global ischemia. However, the receptors (e.g., cell surface or nuclear), intracellular signaling pathways and networks of estrogen-regulated genes that intervene in neuronal apoptosis are as yet unclear. We have shown that estradiol administered at physiological levels for two weeks before ischemia rescues neurons destined to die in the hippocampal CA1 and ameliorates ischemia-induced cognitive deficits in ovariectomized female rats. This regimen of estradiol treatment involves classical intracellular estrogen receptors, transactivation of IGF-1 receptors and stimulation of the ERK/MAPK signaling pathway, which in turn maintains CREB activity in the ischemic CA1. We also find that a single, acute injection of estradiol administrated into the brain ventricle immediately after an ischemic event reduces both neuronal death and cognitive deficits. Because these findings suggest that hormones could be used to treat patients when given after brain ischemia, it is critical to determine whether the same or different pathways mediate this form of neuroprotection. We find that an agonist of the membrane estrogen receptor GPR30 mimics short latency estradiol facilitation of synaptic transmission in the hippocampus. Therefore, we are testing the hypothesis that GPR30 may act together with intracellular estrogen receptors to activate cell signaling pathways to promote neuron survival after global ischemia.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.