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  • 1.
    Blackwell, Kim T.
    et al.
    George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. lackwell, Kim T..
    Salinas, Armando G.
    Tewatia, Parul
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    English, Brad
    Hellgren Kotaleski, Jeanette
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lovinger, David M.
    Molecular mechanisms underlying striatal synaptic plasticity: relevance chronic alcohol consumption and seeking2019In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 49, no 6, p. 768-783Article in journal (Refereed)
    Abstract [en]

    The striatum, the input structure of the basal ganglia, is a major site learning and memory for goal-directed actions and habit formation. iny projection neurons of the striatum integrate cortical, thalamic, d nigral inputs to learn associations, with cortico-striatal synaptic asticity as a learning mechanism. Signaling molecules implicated in naptic plasticity are altered in alcohol withdrawal, which may ntribute to overly strong learning and increased alcohol seeking and nsumption. To understand how interactions among signaling molecules oduce synaptic plasticity, we implemented a mechanistic model of gnaling pathways activated by dopamine D1 receptors, acetylcholine ceptors, and glutamate. We use our novel, computationally efficient mulator, NeuroRD, to simulate stochastic interactions both within and tween dendritic spines. Dopamine release during theta burst and 20-Hz imulation was extrapolated from fast-scan cyclic voltammetry data llected in mouse striatal slices. Our results show that the combined tivity of several key plasticity molecules correctly predicts the currence of either LTP, LTD, or no plasticity for numerous perimental protocols. To investigate spatial interactions, we imulate two spines, either adjacent or separated on a 20-mu m ndritic segment. Our results show that molecules underlying LTP hibit spatial specificity, whereas 2-arachidonoylglycerol exhibits a atially diffuse elevation. We also implement changes in NMDA ceptors, adenylyl cyclase, and G protein signaling that have been asured following chronic alcohol treatment. Simulations under these nditions suggest that the molecular changes can predict changes in naptic plasticity, thereby accounting for some aspects of alcohol use sorder.

  • 2.
    Gomez-Alvarez, Marcelo
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Unit Audiol, Alfred Nobels Alle 10, S-14183 Stockholm, Sweden..
    Gourevitch, Boris
    Sorbonne Univ Paris, Inst Pasteur, INSERM, Unite Genet & Physiol Audit, Paris, France.;CNRS, Paris, France..
    Felix, Richard A., II
    Washington State Univ, Vancouver, WA USA..
    Nyberg, Tobias
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Hernandez-Montiel, Hebert L.
    Univ Autonoma Queretaro, Clin Sistema Nervioso, Lab Neurobiol & Bioingn Celular, Santiago De Queretaro, Mexico..
    Magnusson, Anna K.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Unit Audiol, Alfred Nobels Alle 10, S-14183 Stockholm, Sweden..
    Temporal information in tones, broadband noise, and natural vocalizations is conveyed by differential spiking responses in the superior paraolivary nucleus2018In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 48, no 4, p. 2030-2049Article in journal (Refereed)
    Abstract [en]

    Communication sounds across all mammals consist of multiple frequencies repeated in sequence. The onset and offset of vocalizations are potentially important cues for recognizing distinct units, such as phonemes and syllables, which are needed to perceive meaningful communication. The superior paraolivary nucleus (SPON) in the auditory brainstem has been implicated in the processing of rhythmic sounds. Here, we compared how best frequency tones (BFTs), broadband noise (BBN), and natural mouse calls elicit onset and offset spiking in the mouse SPON. The results demonstrate that onset spiking typically occurs in response to BBN, but not. BFT stimulation, while spiking at the sound offset occurs for both stimulus types. This effect of stimulus bandwidth on spiking is consistent with two of the established inputs to the SPON from the octopus cells (onset spiking) and medial nucleus of the trapezoid body (offset spiking). Natural mouse calls elicit two main spiking peaks. The first spiking peak, which is weak or absent with BFT stimulation, occurs most consistently during the call envelope, while the second spiking peak occurs at the call offset. This suggests that the combined spiking activity in the SPON elicited by vocalizations reflects the entire envelope, that is, the coarse amplitude waveform. Since the output from the SPON is purely inhibitory, it is speculated that, at the level of the inferior colliculus, the broadly tuned first peak may improve the signal-to-noise ratio of the subsequent, more call frequency-specific peak. Thus, the SPON may provide a dual inhibition mechanism for tracking phonetic boundaries in social-vocal communication.

  • 3. Mulder, Jan
    et al.
    Spence, Lauren
    Tortoriello, Giuseppe
    DiNieri, Jennifer A.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Shui, Bo
    Kotlikoff, Michael I.
    Yanagawa, Yuchio
    Aujard, Fabienne
    Hokfelt, Tomas
    Hurd, Yasmin L.
    Harkany, Tibor
    Secretagogin is a Ca2+-binding protein identifying prospective extended amygdala neurons in the developing mammalian telencephalon2010In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 31, no 12, p. 2166-2177Article in journal (Refereed)
    Abstract [en]

    The Ca2+-binding proteins (CBPs) calbindin D28k, calretinin and parvalbumin are phenotypic markers of functionally diverse subclasses of neurons in the adult brain. The developmental dynamics of CBP expression are precisely timed: calbindin and calretinin are present in prospective cortical interneurons from mid-gestation, while parvalbumin only becomes expressed during the early postnatal period in rodents. Secretagogin (scgn) is a CBP cloned from pancreatic beta and neuroendocrine cells. We hypothesized that scgn may be expressed by particular neuronal contingents during prenatal development of the mammalian telencephalon. We find that scgn is expressed in neurons transiting in the subpallial differentiation zone by embryonic day (E)11 in mouse. From E12, scgn+ cells commute towards the extended amygdala and colonize the bed nucleus of stria terminalis, the interstitial nucleus of the posterior limb of the anterior commissure, the dorsal substantia innominata (SI) and the central and medial amygdaloid nuclei. Scgn+ neurons can acquire a cholinergic phenotype in the SI or differentiate into GABA cells in the central amygdala. We also uncover phylogenetic differences in scgn expression as this CBP defines not only neurons destined to the extended amygdala but also cholinergic projection cells and cortical pyramidal cells in the fetal nonhuman primate and human brains, respectively. Overall, our findings emphasize the developmentally shared origins of neurons populating the extended amygdala, and suggest that secretagogin can be relevant to the generation of functional modalities in specific neuronal circuitries.

  • 4.
    Petersson, Marcus E.
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Yoshida, Motoharu
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Low-frequency summation of synaptically activated transient receptor potential channel-mediated depolarizations2011In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 34, no 4, p. 578-593Article in journal (Refereed)
    Abstract [en]

    Neurons sum their input by spatial and temporal integration. Temporally, presynaptic firing rates are converted to dendritic membrane depolarizations by postsynaptic receptors and ion channels. In several regions of the brain, including higher association areas, the majority of firing rates are low. For rates below 20 Hz, the ionotropic receptors alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor will not produce effective temporal summation. We hypothesized that depolarization mediated by transient receptor potential (TRP) channels activated by metabotropic glutamate receptors would be more effective, owing to their slow kinetics. On the basis of voltage-clamp and current-clamp recordings from a rat slice preparation, we constructed a computational model of the TRP channel and its intracellular activation pathway, including the metabotropic glutamate receptor. We show that synaptic input frequencies down to 3-4 Hz and inputs consisting of as few as three to five pulses can be effectively summed. We further show that the time constant of integration increases with increasing stimulation frequency and duration. We suggest that the temporal summation characteristics of TRP channels may be important at distal dendritic arbors, where spatial summation is limited by the number of concurrently active synapses. It may be particularly important in regions characterized by low and irregular rates.

  • 5.
    Petersson, Marcus
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Long-lasting small-amplitude TRP-mediated dendritic depolarizations in CA1 pyramidal neurons are intrinsically stable and originate from distal tuft regions2012In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 36, no 7, p. 2917-2925Article in journal (Refereed)
    Abstract [en]

    In several regions of the nervous system, neurons display bi- or multistable intrinsic properties. Such stable states may be subthreshold and long-lasting, and can appear as a sustained afterdepolarization. In hippocampal CA1 pyramidal neurons, small-amplitude (1 mV) long-lasting (seconds) afterdepolarizations have been reported and are thought to depend on calcium-activated nonselective (CAN) currents recently identified as transient receptor potential (TRP) channels. Continuing our previous experimental and computational work on synaptically metabotropic glutamate receptor (mGluR)-activated TRP currents, we here explore small-amplitude long-lasting depolarizations in a detailed multicompartmental model of a CA1 pyramidal neuron. We confirm a previous hypothesis suggesting that the depolarization results from an interplay of TRP and voltage-gated calcium channels, and contribute to the understanding of the depolarization in several ways. Specifically, we show that: (i) the long-lasting depolarization may be intrinsically stable to weak excitatory and inhibitory input, (ii) the phenomenon is essentially located in distal apical dendrites, (iii) induction is facilitated if simultaneous input arrives at several dendritic branches, and if calcium- and/or mGluR-evoked signals undergo summation, suggesting that both spatial and temporal synaptic summation might be required for the depolarization to occur and (iv) we also show that the integration of inputs to oblique dendrites is strongly modulated by the presence of small-amplitude long-lasting depolarizations in distal tuft dendrites. To conclude, we suggest that small-amplitude long-lasting dendritic depolarizations may contribute to sustaining neural information during behavioural tasks in cases where information is separated in time, as in trace conditioning and delay tasks.

  • 6. Yoshida, Motoharu
    et al.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Hasselmo, Michael E.
    mGluR-dependent persistent firing in entorhinal cortex layer III neurons2008In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 28, no 6, p. 1116-1126Article in journal (Refereed)
    Abstract [en]

    Persistent firing is believed to be a crucial mechanism for memory function including working memory. Recent in vivo and in vitro findings suggest an involvement of metabotropic glutamate receptors (mGluRs) in persistent firing. Using whole-cell patch-recording techniques in a rat entorhinal cortex (EC) slice preparation, we tested whether EC layer III neurons display persistent firing due to mGluR activation, independently of cholinergic activation. Stimulation of the angular bundle drove persistent firing in 90% of the cells in the absence of a cholinergic agonist. The persistent firing was typically stable for > 4.5 min at which point persistent firing was terminated by the experimenter. The average frequency of the persistent firing was 2.1 Hz, ranging from 0.4 to 5.5 Hz. This persistent firing was observed even in the presence of atropine (2 mu M), suggesting that the persistent firing can occur independent of cholinergic activation. Furthermore, ionotropic glutamate and GABAergic synaptic blockers (2 mm kynurenic acid, 100 mu M picrotoxin and 1 mu M CGP55845) did not block the persistent firing. On the other hand, blockers of group I mGluRs (100 mu M LY367385 and 20 mu M MPEP) completely blocked or suppressed the persistent firing. An agonist of group I mGluRs (20 mu M DHPG) greatly enhanced the persistent firing induced by current injection. These results indicate that persistent firing can be driven through group I mGluRs in entorhinal layer III neurons, suggesting that glutamatergic synaptic input alone could enable postsynaptic neurons to hold input signals in the form of persistent firing.

1 - 6 of 6
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