Neuron
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Comparative Study
Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport.
Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. ⋯ A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux.
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Comparative Study
Blanes cells mediate persistent feedforward inhibition onto granule cells in the olfactory bulb.
Inhibitory local circuits in the olfactory bulb play a critical role in determining the firing patterns of output neurons. However, little is known about the circuitry in the major plexiform layers of the olfactory bulb that regulate this output. Here we report the first electrophysiological recordings from Blanes cells, large stellate-shaped interneurons located in the granule cell layer. ⋯ Using paired two-photon guided intracellular recordings, we show that Blanes cells have a presumptive axon and monosynaptically inhibit granule cells. Sensory axon stimulation evokes barrages of EPSPs in Blanes cells that trigger long epochs of persistent spiking; this firing mode was reset by hyperpolarizing membrane potential steps. Persistent firing in Blanes cells may represent a novel mechanism for encoding short-term olfactory information through modulation of tonic inhibitory synaptic input onto bulbar neurons.
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Comparative Study
Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain.
In mammals, the perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by nociceptive sensory neurons. The molecular mechanisms responsible for the specification of distinct sensory modality are, however, largely unknown. We show here that Runx1, a Runt domain transcription factor, is expressed in most nociceptors during embryonic development but in adult mice, becomes restricted to nociceptors marked by expression of the neurotrophin receptor Ret. ⋯ Runx1 also controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a finding with implications for pain therapy.
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Research on the neural systems underlying emotion in animal models over the past two decades has implicated the amygdala in fear and other emotional processes. This work stimulated interest in pursuing the brain mechanisms of emotion in humans. Here, we review research on the role of the amygdala in emotional processes in both animal models and humans. The review is not exhaustive, but it highlights five major research topics that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory, emotional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.
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Comparative Study
Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway.
The requirement for transcription during long-lasting plasticity indicates that signals generated at the synapse must be transported to the nucleus. We have investigated whether the classical active nuclear import pathway mediates intracellular retrograde signal transport in Aplysia sensory neurons and rodent hippocampal neurons. We found that importins localize to distal neuronal processes, including synaptic compartments, where they are well positioned to mediate synapse to nucleus signaling. ⋯ In hippocampal neurons, NMDA receptor activation but not depolarization induced importin nuclear translocation. We further showed that LTP-inducing stimuli recruited active nuclear import in hippocampal slices. Together with our finding that long-term facilitation of Aplysia sensory-motor synapses required active nuclear import, our results indicate that regulation of the active nuclear import pathway plays a critical role in transporting synaptically generated signals into the nucleus during learning-related forms of plasticity.