Multiple Clusters of Release Sites Formed by Individual Thalamic Afferents onto Cortical Interneurons Ensure Reliable Transmission

Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, CA 92093, USA.
Neuron (Impact Factor: 15.05). 07/2011; 71(1):180-94. DOI: 10.1016/j.neuron.2011.05.032
Source: PubMed


Thalamic afferents supply the cortex with sensory information by contacting both excitatory neurons and inhibitory interneurons. Interestingly, thalamic contacts with interneurons constitute such a powerful synapse that even one afferent can fire interneurons, thereby driving feedforward inhibition. However, the spatial representation of this potent synapse on interneuron dendrites is poorly understood. Using Ca imaging and electron microscopy we show that an individual thalamic afferent forms multiple contacts with the interneuronal proximal dendritic arbor, preferentially near branch points. More contacts are correlated with larger amplitude synaptic responses. Each contact, consisting of a single bouton, can release up to seven vesicles simultaneously, resulting in graded and reliable Ca transients. Computational modeling indicates that the release of multiple vesicles at each contact minimally reduces the efficiency of the thalamic afferent in exciting the interneuron. This strategy preserves the spatial representation of thalamocortical inputs across the dendritic arbor over a wide range of release conditions.

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    • "It is possible that larger mEPSCs in FSIs, which are practically absent in PNs, are generated by the release of multiple vesicles. Multiple clusters of release sites formed by individual thalamic afferents onto cortical FSIs were found by the EM study (Bagnall et al., 2011). Multiple vesicle release appears to be due to spontaneous 'sparks' of Ca 2+ from intracellular stores (Emptage et al., 2001; Simkus and Stricker, 2002). "
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    ABSTRACT: Properties of excitatory synaptic responses in fast-spiking interneurons (FSIs) and pyramidal neurons (PNs) are different; however, the mechanisms and determinants of this diversity have not been fully investigated. In the present study, voltage-clamp recording of miniature excitatory post-synaptic currents (mEPSCs) was performed of layer 2-3 FSIs and PNs in the medial prefrontal cortex of rats aged 19-22 days. The average mEPSCs in the FSIs exhibited amplitudes that were two times larger than those of the PNs and with much faster rise and decay. The mEPSC amplitude distributions in both cell types were asymmetric and in FSIs, the distributions were more skewed and had two-times larger coefficients of variation than in the PNs. In PNs but not in FSIs, the amplitude distributions were fitted well by different skewed unimodal functions that have been used previously for this purpose. In the FSIs, the distributions were well approximated only by a sum of two such functions, suggesting the presence of at least two subpopulations of events with different modal amplitudes. According to our estimates, two-thirds of the mEPSCs in FSIs belong to the high-amplitude subpopulation, and the modal amplitude in this subpopulation is approximately two times larger than that in the low-amplitude subpopulation. Using different statistical models, varying binning size, and data subsets, we confirmed the robustness and consistency of these findings. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
    Neuroscience 06/2015; 301. DOI:10.1016/j.neuroscience.2015.06.034 · 3.36 Impact Factor
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    • "Although the functional impact of these expression changes is unclear, it is thought that widespread disruption in the functioning of these cells could lead to significant changes in the cortical excitatory–inhibitory balance (Lewis et al., 2012). Furthermore, compared with cortical pyramidal cells, fast spiking cells receive particularly strong monosynaptic projections from TC cells (Cruikshank et al., 2007; Bagnall et al., 2011), which may underlie the strong activation and phase locking of these cells during spindle oscillations (Gardner et al., 2013). "
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    ABSTRACT: The neurophysiology of non-rapid eye movement sleep is characterized by the occurrence of neural network oscillations with distinct origins and frequencies, which act in concert to support sleep-dependent information processing. Thalamocortical circuits generate slow (0.25–4 Hz) oscillations reflecting synchronized temporal windows of cortical activity, whereas concurrent waxing and waning spindle oscillations (8–15 Hz) act to facilitate cortical plasticity. Meanwhile, fast (140–200 Hz) and brief (< 200 ms) hippocampal ripple oscillations are associated with the reactivation of neural assemblies recruited during prior wakefulness. The extent of the forebrain areas engaged by these oscillations, and the variety of cellular and synaptic mechanisms involved, make them sensitive assays of distributed network function. Each of these three oscillations makes crucial contributions to the offline memory consolidation processes supported by non-rapid eye movement sleep. Slow, spindle and ripple oscillations are therefore potential surrogates of cognitive function and may be used as diagnostic measures in a range of brain diseases. We review the evidence for disrupted slow, spindle and ripple oscillations in schizophrenia, linking pathophysiological mechanisms to the functional impact of these neurophysiological changes and drawing links with the cognitive symptoms that accompany this condition. Finally, we discuss potential therapies that may normalize the coordinated activity of these three oscillations in order to restore healthy cognitive function.
    European Journal of Neuroscience 04/2014; 39(7). DOI:10.1111/ejn.12533 · 3.18 Impact Factor
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    • "It is currently unclear which of these models likely represents the true mechanism in the neocortex, and potentially both are viable, depending on the physiological state of the cortex [11]. However, it seems that the WB model may more accurately represent the situation in the neocortex, as neocortical basket cells receive much stronger and more reliable glutamatergic thalamocortical excitation than pyramidal cells [12], [13]. However, there are limitations to the WB model and its subsequent modifications, most importantly that it does not include realistic synaptic depression and that it is lacking the autaptic connections that neocortical basket cells express [14], [15], [16]. "
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    ABSTRACT: Computational models of gamma oscillations have helped increase our understanding of the mechanisms that shape these 40-80 Hz cortical rhythms. Evidence suggests that interneurons known as basket cells are responsible for the generation of gamma oscillations. However, current models of gamma oscillations lack the dynamic short term synaptic plasticity seen at basket cell-basket cell synapses as well as the large autaptic synapses basket cells are known to express. Hence, I sought to extend the Wang-Buzsáki model of gamma oscillations to include these features. I found that autapses increased the synchrony of basket cell membrane potentials across the network during neocortical gamma oscillations as well as allowed the network to oscillate over a broader range of depolarizing drive. I also found that including realistic synaptic depression filtered the output of the network. Depression restricted the network to oscillate in the 60-80 Hz range rather than the 40-120 Hz range seen in the standard model. This work shows the importance of including accurate synapses in any future model of gamma oscillations.
    PLoS ONE 02/2014; 9(2):e89995. DOI:10.1371/journal.pone.0089995 · 3.23 Impact Factor
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