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GABAergic Projections from the Medial Septum Selectively Inhibit Interneurons in the Medial Entorhinal Cortex

Alfredo Gonzalez-Sulser, Daniel Parthier, Antonio Candela, Christina McClure, Hugh Pastoll, Derek Garden, Gülşen Sürmeli and Matthew F. Nolan
Journal of Neuroscience 10 December 2014, 34 (50) 16739-16743; DOI: https://doi.org/10.1523/JNEUROSCI.1612-14.2014
Alfredo Gonzalez-Sulser
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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  • ORCID record for Alfredo Gonzalez-Sulser
Daniel Parthier
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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Antonio Candela
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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Christina McClure
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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Hugh Pastoll
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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Derek Garden
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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Gülşen Sürmeli
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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Matthew F. Nolan
Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom
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    Figure 1.

    Labeling of axonal projections from MS to MEC. A, Diagram illustrating AAV injection site in the MS and labeled axonal projections (red) to the MEC. B, ChR2-mCherry-expressing cells (red) in a horizontal section containing the MS and also labeled with NeuroTrace (green). C, Horizontal section of the MEC, with cell bodies labeled with NeuroTrace (top left), MS axons expressing ChR2-mCherry (top right), and merged image (bottom left). Normalized mCherry fluorescence quantification reveals differences between layers (bottom right; *p < 0.05, Tukey's test). Scale bars, 200 μm.

  • Figure 2.
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    Figure 2.

    Responses to activation of MS fibers across different MEC cell types. A, Examples of averaged (n = 5) IPSPs and EPSPs evoked by photostimulation (blue bar) of ChR2-positive MS axons recorded at holding potentials on either side of the chloride reversal potential. No stimulation (gray), GABAAR (red), and iGluR (blue) blockade traces are also shown. B, Representative responses of FS interneurons, LTS interneurons, NSPCs, and SCs to injection of positive and negative current steps. The cells are the same as in A. C, Streptavidin (red) staining of biocytin-filled cells recorded in A and B. ChR2-venus MS axons are in green. Inset displays 40× image of dendritic regions indicated in the main image, showing the absence and presence of spines in inhibitory and excitatory neurons, respectively. Scale bar, 50 μm.

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    Figure 3.

    MS GABAergic fibers target FS and LTS interneurons in MEC. A, Fraction of neurons of each cell type responding to photostimulation in MEC. Numbers indicate responding cells and total number of recorded cells. B, Cumulative probability plots of IPSP amplitude, latency, rise, and decay time constants for responsive inhibitory neurons. C, Fraction of FS and LTS interneurons in each layer receiving GABAergic input from the MS.

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    Figure 4.

    MS GABAergic fibers entrain FS and LTS interneuron firing. A, Voltage-clamp responses in control (black), in the presence of iGluR and AChR antagonists (blue); and in the presence of iGluR, AChR, and GABAAR antagonists (red). Holding potential, 0 mV. B, Example responses of an FS interneuron to activation of MS GABAergic input at theta frequency (10 Hz). Mean trace, black; individual traces, gray. C, Ten consecutive responses from B on an expanded time scale. D, Normalized IPSP amplitude plotted as a function of stimulus number. E, Example response during the injection of current sufficient for maintained action potential firing without (left) and with (right) theta frequency activation of MS inputs to an FS neuron. F, Ten consecutive responses triggered from the time of each light stimulus illustrate entrainment of rebound spikes. G, Binned counts from 100 stimuli of action potentials as a function of time from the light pulse, illustrating measurement of pause time (red arrow) and frequency (blue arrow).

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The Journal of Neuroscience: 34 (50)
Journal of Neuroscience
Vol. 34, Issue 50
10 Dec 2014
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GABAergic Projections from the Medial Septum Selectively Inhibit Interneurons in the Medial Entorhinal Cortex
Alfredo Gonzalez-Sulser, Daniel Parthier, Antonio Candela, Christina McClure, Hugh Pastoll, Derek Garden, Gülşen Sürmeli, Matthew F. Nolan
Journal of Neuroscience 10 December 2014, 34 (50) 16739-16743; DOI: 10.1523/JNEUROSCI.1612-14.2014

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GABAergic Projections from the Medial Septum Selectively Inhibit Interneurons in the Medial Entorhinal Cortex
Alfredo Gonzalez-Sulser, Daniel Parthier, Antonio Candela, Christina McClure, Hugh Pastoll, Derek Garden, Gülşen Sürmeli, Matthew F. Nolan
Journal of Neuroscience 10 December 2014, 34 (50) 16739-16743; DOI: 10.1523/JNEUROSCI.1612-14.2014
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Keywords

  • gamma
  • interneuron
  • lamina organization
  • medial entorhinal cortex
  • medial septum
  • theta

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