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  1. Article: Thalamic circuitry and thalamocortical synchrony.

    Jones, Edward G

    Philosophical transactions of the Royal Society of London. Series B, Biological sciences

    2002  Volume 357, Issue 1428, Page(s) 1659–1673

    Abstract: The corticothalamic system has an important role in synchronizing the activities of thalamic and ... populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious ... at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are ...

    Abstract The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the gamma-amino butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage-dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high- or low-frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low-frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious events.
    MeSH term(s) Animals ; Cerebral Cortex/anatomy & histology ; Cerebral Cortex/physiology ; Mammals ; Microscopy, Immunoelectron ; Neural Pathways/anatomy & histology ; Neural Pathways/physiology ; Primates ; Synapses/physiology ; Thalamus/anatomy & histology ; Thalamus/physiology ; gamma-Aminobutyric Acid/physiology
    Chemical Substances gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2002-12-29
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 208382-6
    ISSN 1471-2970 ; 0962-8436 ; 0080-4622 ; 0264-3839
    ISSN (online) 1471-2970
    ISSN 0962-8436 ; 0080-4622 ; 0264-3839
    DOI 10.1098/rstb.2002.1168
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  2. Article: Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus.

    Dai, Qian / Qu, Tong / Shen, Guoming / Wang, Haitao

    Frontiers in neuroscience

    2024  Volume 18, Page(s) 1368816

    Abstract: ... neural activities and increased synchrony due to an imbalance between excitation and inhibition ... tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging ... involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored ...

    Abstract Introduction: Subjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored.
    Methods: We induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons.
    Results: Salicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex.
    Discussion: This finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.
    Language English
    Publishing date 2024-04-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2024.1368816
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  3. Article ; Online: Vagus Nerve Stimulation Modulates Phase-Amplitude Coupling in Thalamic Local Field Potentials.

    Warsi, Nebras M / Yan, Han / Wong, Simeon M / Yau, Ivanna / Breitbart, Sara / Go, Cristina / Gorodetsky, Carolina / Fasano, Alfonso / Kalia, Suneil K / Rutka, James T / Vaughan, Kerry / Ibrahim, George M

    Neuromodulation : journal of the International Neuromodulation Society

    2022  Volume 26, Issue 3, Page(s) 601–606

    Abstract: ... by the modulation of afferent thalamocortical circuitry. Cross-frequency phase-amplitude coupling (PAC) is ... 2) nuclei in five patients with tandem thalamic deep brain stimulation and VNS to study ... we leverage local field potential (LFP) recordings from the centromedian (CM) (n = 3) and anterior (ATN) (n ...

    Abstract Objective: The antiseizure effects of vagus nerve stimulation (VNS) are thought to be mediated by the modulation of afferent thalamocortical circuitry. Cross-frequency phase-amplitude coupling (PAC) is a mechanism of hierarchical network coordination across multiple spatiotemporal scales. In this study, we leverage local field potential (LFP) recordings from the centromedian (CM) (n = 3) and anterior (ATN) (n = 2) nuclei in five patients with tandem thalamic deep brain stimulation and VNS to study neurophysiological changes in the thalamus in response to VNS.
    Materials and methods: Bipolar LFP data were recorded from contact pairs spanning target nuclei in VNS "on" and "off" states.
    Results: Active VNS was associated with increased PAC between theta, alpha, and beta phase and gamma amplitude in CM (q < 0.05). Within the ATN, PAC changes also were observed, although these were less robust. In both nuclei, active VNS also modulated interhemispheric bithalamic functional connectivity.
    Conclusions: We report that VNS is associated with enhanced PAC and coordinated interhemispheric interactions within and between thalamic nuclei, respectively. These findings advance understanding of putative neurophysiological effects of acute VNS and contextualize previous animal and human studies showing distributed cortical synchronization after VNS.
    MeSH term(s) Animals ; Humans ; Vagus Nerve Stimulation ; Thalamus
    Language English
    Publishing date 2022-07-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1500372-3
    ISSN 1525-1403 ; 1094-7159
    ISSN (online) 1525-1403
    ISSN 1094-7159
    DOI 10.1016/j.neurom.2022.05.001
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  4. Article: Causal Role of Thalamic Interneurons in Brain State Transitions: A Study Using a Neural Mass Model Implementing Synaptic Kinetics.

    Bhattacharya, Basabdatta Sen / Bond, Thomas P / O'Hare, Louise / Turner, Daniel / Durrant, Simon J

    Frontiers in computational neuroscience

    2016  Volume 10, Page(s) 115

    Abstract: ... about the role and impact of IN on thalamocortical dynamics in both experimental and model-based research. We use ... synchronous oscillations within the alpha band in both TCR and TRN. These observations conform to experimental ... a neural mass computational model of the LGN with three neural populations viz. IN, thalamocortical relay ...

    Abstract Experimental studies on the Lateral Geniculate Nucleus (LGN) of mammals and rodents show that the inhibitory interneurons (IN) receive around 47.1% of their afferents from the retinal spiking neurons, and constitute around 20-25% of the LGN cell population. However, there is a definite gap in knowledge about the role and impact of IN on thalamocortical dynamics in both experimental and model-based research. We use a neural mass computational model of the LGN with three neural populations viz. IN, thalamocortical relay (TCR), thalamic reticular nucleus (TRN), to study the causality of IN on LGN oscillations and state-transitions. The synaptic information transmission in the model is implemented with kinetic modeling, facilitating the linking of low-level cellular attributes with high-level population dynamics. The model is parameterized and tuned to simulate alpha (8-13 Hz) rhythm that is dominant in both Local Field Potential (LFP) of LGN and electroencephalogram (EEG) of visual cortex in an awake resting state with eyes closed. The results show that: First, the response of the TRN is suppressed in the presence of IN in the circuit; disconnecting the IN from the circuit effects a dramatic change in the model output, displaying high amplitude synchronous oscillations within the alpha band in both TCR and TRN. These observations conform to experimental reports implicating the IN as the primary inhibitory modulator of LGN dynamics in a cognitive state, and that reduced cognition is achieved by suppressing the TRN response. Second, the model validates steady state visually evoked potential response in humans corresponding to periodic input stimuli; however, when the IN is disconnected from the circuit, the output power spectra do not reflect the input frequency. This agrees with experimental reports underpinning the role of IN in efficient retino-geniculate information transmission. Third, a smooth transition from alpha to theta band is observed by progressive decrease of neurotransmitter concentrations in the synaptic clefts; however, the transition is abrupt with removal of the IN circuitry in the model. The results imply a role of IN toward maintaining homeostasis in the LGN by suppressing any instability that may arise due to anomalous synaptic attributes.
    Language English
    Publishing date 2016-11-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452964-3
    ISSN 1662-5188
    ISSN 1662-5188
    DOI 10.3389/fncom.2016.00115
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  5. Article: Thalamic synchrony and dynamic regulation of global forebrain oscillations.

    Huguenard, John R / McCormick, David A

    Trends in neurosciences

    2007  Volume 30, Issue 7, Page(s) 350–356

    Abstract: ... critically on reciprocal synaptic connectivity between excitatory thalamocortical relay neurons and ... into larger thalamocortical networks to generate sleep spindles and spike-wave discharge of generalized ... Feedforward and feedback connections between cortex and thalamus reinforce the thalamic oscillatory activity ...

    Abstract The circuitry within the thalamus creates an intrinsic oscillatory unit whose function depends critically on reciprocal synaptic connectivity between excitatory thalamocortical relay neurons and inhibitory thalamic reticular neurons along with a robust post-inhibitory rebound mechanism in relay neurons. Feedforward and feedback connections between cortex and thalamus reinforce the thalamic oscillatory activity into larger thalamocortical networks to generate sleep spindles and spike-wave discharge of generalized absence epilepsy. The degree of synchrony within the thalamic network seems to be crucial in determining whether normal (spindle) or pathological (spike-wave) oscillations occur, and recent studies show that regulation of excitability in the reticular nucleus leads to dynamical modulation of the state of the thalamic circuit and provide a basis for explaining how a variety of unrelated genetic alterations might lead to the spike-wave phenotype. In addition, given the central role of the reticular nucleus in generating spike-wave discharge, these studies have suggested specific interventions that would prevent seizures while still allowing normal spindle generation to occur. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).
    MeSH term(s) Animals ; Biological Clocks/physiology ; Nonlinear Dynamics ; Prosencephalon/physiology ; Thalamus/physiology
    Language English
    Publishing date 2007-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 282488-7
    ISSN 1878-108X ; 0166-2236 ; 0378-5912
    ISSN (online) 1878-108X
    ISSN 0166-2236 ; 0378-5912
    DOI 10.1016/j.tins.2007.05.007
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  6. Article: Cortically-induced coherence of a thalamic-generated oscillation.

    Destexhe, A / Contreras, D / Steriade, M

    Neuroscience

    1999  Volume 92, Issue 2, Page(s) 427–443

    Abstract: ... investigated by computational models of interacting cortical and thalamic neurons, including their intrinsic ... compatible with a powerful role for the cortex in triggering and synchronizing oscillations generated ... firing patterns and various synaptic receptors present in the circuitry. The model indicates ...

    Abstract Oscillatory patterns in neocortical electrical activity show various degrees of large-scale synchrony depending on experimental conditions, but the exact mechanisms underlying these variations of coherence are not known. Analysis of multisite local field potentials revealed that the coherence of spindle oscillations varied during different states. During natural sleep, the coherence was remarkably high over cortical distances of several millimeters, but could be disrupted by artificial cortical depression, similar to the effect of barbiturates. Possible mechanisms for these variations of coherence were investigated by computational models of interacting cortical and thalamic neurons, including their intrinsic firing patterns and various synaptic receptors present in the circuitry. The model indicates that modulation of the excitability of the cortex can affect spatiotemporal coherence with no change in the thalamus. The highest level of coherence was obtained by enhancing the excitability of cortical pyramidal cells, simulating the action of neuromodulators such as acetylcholine and noradrenaline. The underlying mechanism was due to cortex-thalamus-cortex loops in which a more excitable cortical network generated a more powerful and coherent feedback onto the thalamus, resulting in highly coherent oscillations, similar to the properties measured during natural sleep. In conclusion, these experiments and models are compatible with a powerful role for the cortex in triggering and synchronizing oscillations generated in the thalamus, through corticothalamic feedback projections. The model suggests that intracortical mechanisms may be responsible for synchronizing oscillations over cortical distances of several millimeters through cortex-thalamus-cortex loops, thus providing a possible cellular mechanism to explain the genesis of large-scale coherent oscillations in the thalamocortical system.
    MeSH term(s) Anesthesia ; Animals ; Cats ; Cerebral Cortex/physiology ; Cortical Spreading Depression/physiology ; Excitatory Postsynaptic Potentials/physiology ; Hypnotics and Sedatives ; Membrane Potentials/physiology ; Models, Neurological ; Pyramidal Cells/physiology ; Sleep/physiology ; Synapses/physiology ; Thalamic Nuclei/physiology
    Chemical Substances Hypnotics and Sedatives
    Language English
    Publishing date 1999
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196739-3
    ISSN 1873-7544 ; 0306-4522
    ISSN (online) 1873-7544
    ISSN 0306-4522
    DOI 10.1016/s0306-4522(99)00024-x
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  7. Article: Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells.

    Destexhe, A / Contreras, D / Steriade, M

    Journal of neurophysiology

    1998  Volume 79, Issue 2, Page(s) 999–1016

    Abstract: ... that the large-scale synchrony of spindle oscillations in vivo is the result of thalamocortical interactions ... interneurons, thalamic reticular (RE) and thalamocortical (TC) relay cells, on the basis of voltage-clamp data ... patterns of oscillations and synchrony similar to in vivo recordings. The model also emphasizes ...

    Abstract Early studies have shown that spindle oscillations are generated in the thalamus and are synchronized over wide cortical territories. More recent experiments have shown that this large-scale synchrony depends on the integrity of corticothalamic feedback. Previously proposed mechanisms emphasized exclusively intrathalamic mechanisms to generate the synchrony of these oscillations. In the present paper, we propose a cellular mechanism in which the synchrony is dependent of a mutual interaction between cortex and thalamus. This cellular mechanism is tested by computational models consisting of pyramidal cells, interneurons, thalamic reticular (RE) and thalamocortical (TC) relay cells, on the basis of voltage-clamp data on intrinsic currents and synaptic receptors present in the circuitry. The model suggests that corticothalamic feedback must operate on the thalamus mainly through excitation of GABAergic RE neurons, therefore recruiting relay cells essentially through inhibition and rebound. We provide experimental evidence for such dominant inhibition in the lateral posterior nucleus. In these conditions, the model shows that cortical discharges optimally evoked thalamic oscillations. This feature is essential to the present cellular mechanism and is also consistently observed experimentally. The model further shows that, with this type of corticothalamic feedback, cortical discharges recruited large areas of the thalamus because of the divergent cortex-to-RE and RE-to-TC axonal projections. Consequently, the thalamocortical network generated patterns of oscillations and synchrony similar to in vivo recordings. The model also emphasizes the important role of the modulation of the Ih current by calcium in TC cells. This property conferred a relative refractoriness to the entire network, a feature also observed experimentally, as we show here. Further, the same property accounted for various spatiotemporal features of oscillations, such as systematic propagation after low-intensity cortical stimulation, local oscillations, and more generally, a high variability in the patterns of spontaneous oscillations, similar to in vivo recordings. We propose that the large-scale synchrony of spindle oscillations in vivo is the result of thalamocortical interactions in which the corticothalamic feedback acts predominantly through the RE nucleus. Several predictions are suggested to test the validity of this model.
    MeSH term(s) Animals ; Cats ; Cerebral Cortex/physiology ; Evoked Potentials/physiology ; Excitatory Postsynaptic Potentials/physiology ; Feedback ; Interneurons/physiology ; Ion Channel Gating ; Membrane Potentials ; Models, Neurological ; Pyramidal Cells/physiology ; Receptors, AMPA/physiology ; Receptors, GABA/physiology ; Receptors, Neurotransmitter/physiology ; Synaptic Transmission ; Thalamic Nuclei/cytology ; Thalamic Nuclei/physiology
    Chemical Substances Receptors, AMPA ; Receptors, GABA ; Receptors, Neurotransmitter
    Language English
    Publishing date 1998-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80161-6
    ISSN 1522-1598 ; 0022-3077
    ISSN (online) 1522-1598
    ISSN 0022-3077
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  8. Article ; Online: Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons.

    Zhang, Yi / Mori, Mayra / Burgess, Daniel L / Noebels, Jeffrey L

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2002  Volume 22, Issue 15, Page(s) 6362–6371

    Abstract: ... in thalamocortical circuitry and enhance the abnormal rhythmicity associated with absence epilepsy. Mutations ... thalamocortical synchronization and absence epilepsy in tg, lh, and stg mice. ... in thalamic cells of tottering (tg; Cav2.1/alpha1A subunit), lethargic (lh; beta4 subunit), and stargazer (stg ...

    Abstract Ca2+ currents, especially those activated at low voltages (LVA), influence burst generation in thalamocortical circuitry and enhance the abnormal rhythmicity associated with absence epilepsy. Mutations in several genes for high-voltage-activated (HVA) Ca2+ channel subunits are linked to spike-wave seizure phenotypes in mice; however, none of these mutations are predicted to increase intrinsic membrane excitability or directly enhance LVA currents. We examined biophysical properties of both LVA and HVA Ca2+ currents in thalamic cells of tottering (tg; Cav2.1/alpha1A subunit), lethargic (lh; beta4 subunit), and stargazer (stg; gamma2 subunit) brain slices. We observed 46, 51, and 45% increases in peak current densities of LVA Ca2+ currents evoked at -50 mV from -110 mV in tg, lh, and stg mice, respectively, compared with wild type. The half-maximal voltages for steady-state inactivation of LVA currents were shifted in a depolarized direction by 7.5-13.5 mV in all three mutants, although no alterations in the time-constant for recovery from inactivation of LVA currents were found. HVA peak current densities in tg and stg were increased by 22 and 45%, respectively, and a 5 mV depolarizing shift of the activation curve was observed in lh. Despite elevated LVA amplitudes, no alterations in mRNA expression of the genes mediating T-type subunits, Cav3.1/alpha1G, Cav3.2/alpha1H, or Cav3.3/alpha1I, were detected in the three mutants. Our data demonstrate that mutation of Cav2.1 or regulatory subunit genes increases intrinsic membrane excitability in thalamic neurons by potentiating LVA Ca2+ currents. These alterations increase the probability for abnormal thalamocortical synchronization and absence epilepsy in tg, lh, and stg mice.
    MeSH term(s) Animals ; Calcium/metabolism ; Calcium Channels/genetics ; Calcium Channels/metabolism ; Calcium Channels, N-Type/genetics ; Calcium Channels, N-Type/metabolism ; Disease Models, Animal ; Epilepsy, Absence/etiology ; Epilepsy, Absence/metabolism ; Gene Expression ; In Situ Hybridization ; In Vitro Techniques ; Membrane Potentials/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Neurologic Mutants ; Mutation ; Neurons/metabolism ; Patch-Clamp Techniques ; Protein Subunits ; RNA, Messenger/metabolism ; Thalamus/cytology ; Thalamus/metabolism
    Chemical Substances Calcium Channels ; Calcium Channels, N-Type ; Protein Subunits ; RNA, Messenger ; voltage-dependent calcium channel (P-Q type) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2002-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 20026656
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