Properties of Excitatory Synaptic Responses in Fast-spiking Interneurons and Pyramidal Cells from Monkey and Rat Prefrontal Cortex

Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213-2593, USA.
Cerebral Cortex (Impact Factor: 8.67). 05/2006; 16(4):541-52. DOI: 10.1093/cercor/bhj002
Source: PubMed


In the prefrontal cortex (PFC) during working memory tasks fast-spiking (FS) interneurons might shape the spatial selectivity of pyramidal cell firing. In order to provide time control of pyramidal cell activity, incoming excitatory inputs should excite FS interneurons more vigorously than pyramidal cells. This can be achieved if subthreshold excitatory responses of interneurons are considerably stronger and faster than those in pyramidal neurons. Here we compared the functional properties of excitatory post-synaptic potentials (EPSPs) between pyramidal cells and FS interneurons in slices from monkey dorsolateral PFC and rat prelimbic cortex. Miniature, unitary (in connected pairs or by minimal stimulation) and compound (evoked by electrical stimulation of the white matter) EPSPs were recorded in whole cell mode. We found that EPSPs were significantly larger and faster in FS interneurons than those recorded from pyramidal cells, consistent with the idea of more efficient recruitment of FS interneurons compared to pyramidal neurons. Similar results were obtained in monkey and rat PFC, suggesting a stable role of FS interneurons in this circuitry across species.

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Available from: Sven Kroener, Oct 06, 2015
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    • "In agreement with the previously reported data (Povysheva et al., 2006), the mEPSCs in the FSIs had "
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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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    • "Inhibitory mIPSCs and miniature excitatory synaptic currents (mEPSCs) could regulate interneuron activity in vivo, when firing activity in the monkey DLPFC network is low. In FS neurons of monkey DLPFC, the mEPSC frequency is ϳ20 Hz (Povysheva et al. 2006), thus significantly higher than mIPSP and mIPSC frequency (ϳ4 Hz; see Figs. 4 and 8). A high mEPSC-to-mIPSC ratio could make monkey DLPFC FS neurons readily responsive to external inputs arriving when the local network is in a low-firing activity state. "
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    ABSTRACT: In rodent cortex, GABAA receptor (GABAAR)-mediated synapses are a significant source of input onto GABA neurons, and the properties of these inputs vary among GABA neuron subtypes that differ in molecular markers and firing patterns. Some features of cortical interneurons are different between rodents and primates, but it is not known if inhibition of GABA neurons is prominent in the primate cortex and, if so, whether these inputs show heterogeneity across GABA neuron subtypes. We thus studied GABAAR-mediated miniature synaptic events in GABAergic interneurons in layer 3 of monkey dorsolateral prefrontal cortex (DLPFC). Interneurons were identified based on their firing pattern as fast spiking (FS), regular spiking (RS), burst spiking (BS) or irregular spiking (IS). Miniature synaptic events were common in all of the recorded interneurons, and the frequency of these events was highest in FS neurons. The amplitude and kinetics of mIPSPs also differed between DLPFC interneuron subtypes in a manner correlated with their input resistance and membrane time constant. FS neurons had the fastest mIPSP decay times and the strongest effects of the GABAAR modulator zolpidem, suggesting that the distinctive properties of inhibitory synaptic inputs onto FS cells are in part conferred by GABAARs containing α1 subunits. Moreover, mIPSCs differed between FS and RS interneurons in a manner consistent with the mIPSP findings. These results show that in the monkey DLPFC, GABAAR-mediated synaptic inputs are prominent in layer 3 interneurons and may differentially regulate the activity of different interneuron subtypes. Copyright © 2014, Journal of Neurophysiology.
    Journal of Neurophysiology 12/2014; 113(6):jn.00799.2014. DOI:10.1152/jn.00799.2014 · 2.89 Impact Factor
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    • "Parvalbumin-positive interneurons, the major subpopulation of GABAergic interneurons, which are characterized by the fast-spiking discharge pattern, are very important in controlling brain excitability (Morris et al. 1999). Parvalbumin interneurons can release GABA and provide inhibitory postsynaptic potentials to regulate the activity of cortical pyramidal neurons and glutamate neurotransmission (Povysheva et al. 2006). In addition, the function of parvalbumin interneurons is intimately linked to the generation of gamma oscillation (Cardin et al. 2009; Sohal et al. 2009; Volman et al. 2011), an emergent property of cortical circuits linked to information processing and working memory (Jensen et al. 2007), and the disruption of parvalbumin interneurons contributes to the pathogenesis of depression (Liu et al. 2012). "
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    ABSTRACT: Increasing evidence underscores the strong, rapid, and sustained antidepressant properties of ketamine with a good tolerability profile in patients with depression; however, the underlying mechanisms are not fully elucidated. Neuregulin 1 (NRG1) is a bipolar disorder susceptibility gene and a biomarker of major depressive disorder, which regulates pyramidal neuron activity via ErbB4 in parvalbumin interneurons. Moreover, NRG1-ErbB4 signaling is reported to play a key role in the modulation of synaptic plasticity through regulating the neurotransmission. We therefore hypothesized that hypofunction of NRG1-ErbB4 signaling in parvalbumin interneurons is involved in the process of ketamine exerting rapid antidepressant actions in rats subjected to the forced swimming test (FST). The results showed that ketamine reduced the immobility time and latency to feed of rats receiving the FST, downregulated the levels of NRG1, phosphorylated ErbB4 (p-ErbB4), parvalbumin, 67-kDA isoform of glutamic acid decarboxylase (GAD67), gamma-aminobutyric acid (GABA), and upregulated the levels of glutamate in the rat prefrontal cortex and hippocampus. Pretreatment with NRG1 abolished both ketamine's antidepressant effects and ketamine-induced reduction in p-ErbB4, parvalbumin, GAD67, and GABA levels and increase in glutamate levels. These results suggest that the downregulation of NRG1-ErbB4 signaling in parvalbumin interneurons in the rat brain may be a mechanism underlying ketamine's antidepressant properties.
    Journal of Molecular Neuroscience 03/2014; 54(2). DOI:10.1007/s12031-014-0277-8 · 2.34 Impact Factor
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