Research ArticleNEUROSCIENCE

Cell type–differential modulation of prefrontal cortical GABAergic interneurons on low gamma rhythm and social interaction

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Science Advances  22 Jul 2020:
Vol. 6, no. 30, eaay4073
DOI: 10.1126/sciadv.aay4073
  • Fig. 1 Optogenetic tagging and unit classification of mPFC neurons.

    (A) Diagram showing optogenetic tagging and electrophysiological recording using an optrode. (B) Location of unilateral optic fiber and ChR2 expression in PV INs. PrL, prelimbic; IL, infralimbic; DAPI, 4′,6-diamidino-2-phenylindole. Scale bars, 200 μm (left) and 30 μm (right). (C) The same as (B) but for SST INs. (D) Example recording of spontaneous and light-evoked spikes from an opto-tagged PV IN. Blue ticks, light pulses (20 Hz). (E) Overlay of light-evoked (blue) and averaged spontaneous (red) spike waveforms from the example unit. (F) Raster plot of multiple trials showing spike responses to light stimuli at 20 and 40 Hz of the example unit. (G to I) The same as (D to F) but for an opto-tagged SST IN. (J) Raster plot of a light-activated PV IN (top) and an inhibited WS neuron (bottom) recorded from the same tetrode, both aligned to light onset. (K) The same as (J) but for an SST IN. (L) Summary of three types of mPFC neurons studied in the present study. Dark triangles, WS putative pyramidal cells (n = 174); blue circles, putative PV INs and opto-tagged PV INs (n = 27); green diamonds: opto-tagged SST INs (n = 15).

  • Fig. 2 Firing responses of WS, PV, and SST neurons during social interaction.

    (A) Schematic illustration of electrophysiological recording paradigm. (B) Average spike waveforms of a WS (top), PV (middle), and SST neuron (bottom) recorded through four tetrode channels. Shaded areas indicate SEMs. (C) Heat map showing the firing rate of an example WS neuron. Warmer colors indicate higher firing rates. (D) Raster plot of spikes of the example WS neuron shown in (C) during five individual interactions in neutral zone (top) or social zone (bottom). (E) Correlation of firing rate in social zone versus neutral zone for individual WS neurons (n = 174). Orange and green circles indicate individual units with significantly higher or lower firing rates in social zone, respectively. Gray circles indicate neurons with no significant difference in firing rates. Inset: Proportions of WS neurons with significantly increased rates, decreased rates, or no change in rates upon social interaction (Student’s t test). (F to H) The same as (C to E) but for PV INs. Open circles (n = 13) and filled circles (n = 14) indicate putative and opto-tagged PV INs. (I to K) The same as (C to E) but for SST INs. All circles indicate opto-tagged SST INs (n = 15).

  • Fig. 3 Social interaction is characterized by an elevated low gamma power of mPFC LFPs.

    (A and B) Time course of mPFC raw LFP (top), band-filtered LFP (30 to 40 Hz; middle), and spectrogram (20 to 80 Hz; bottom) from a mouse exploring the neutral zone (A) or engaging in social interaction (B) during three-chambered social approach task. The time “0” refers to the onset of an interaction event. Warmer colors indicate enhanced power. (C) Averaged relative mPFC LFP power when test mice explored the neutral zone (black) or interacted with a stimulus mouse (red). Shaded areas indicate SEM. (D) Statistics of LFP power at different gamma frequency bands. Note the power at the low gamma band (20 to 50 Hz) is selectively enhanced when mice engaged in social interaction. Error bars indicate means ± SEM (n = 8 mice). ***P < 0.001, paired t test. (E to H) The same as (A to D) but for object interaction test. Note that there is no significant difference in LFP power between neutral cage explorations and object cage explorations.

  • Fig. 4 Pharmacogenetic inhibition of mPFC PV INs impairs social interaction.

    (A) Location of viral infection (left) and hM4D expression in PV INs (right). Scale bars, 200 (left) and 30 μm (right). (B) Comparison of spontaneous spikes of PV INs before and after CNO administration. Error bars indicate means ± SEM (n = 6). ***P < 0.001, paired t test. (C) Relative mPFC LFP power upon social interaction before and after CNO administration. Shaded areas indicate SEM. Error bars indicate means ± SEM (n = 6 sites from three mice). **P < 0.01, paired t test. (D) Heat maps showing the locations of an EYFP-expressing control mouse (left) and an hM4D-expressing mouse (right) following CNO administration. (E and F) Quantification of time spent by hM4D and EYFP mice in each chamber (E) or each zone (F). Note that social interaction index was significantly smaller in hM4D mice. Error bars indicate means ± SEM (EYFP, n = 9; hM4D, n = 9). *P < 0.05, **P < 0.01, and ****P < 0.0001. Time in chamber or zone: two-way analysis of variance (ANOVA) and Bonferroni multiple comparison post hoc tests; interaction index: unpaired t test.

  • Fig. 5 Activation of PV INs at low gamma frequency produces prosocial effect.

    (A) Diagram showing bilateral optogenetic manipulation in freely moving mice. (B) Placement of optic fibers for photostimulation of mPFC FS-PV INs in a PV-Cre mouse bilaterally injected with ChR2-mCherry. Scale bar, 200 μm. (C) Left: Example spectral power of LFP with (blue) and without (black) light stimuli of PV INs at 40 Hz. Shaded areas indicate SEMs. Right: Comparison of relative LFP gamma power between baseline (black) and light stimuli (blue). Error bars indicate means ± SEM (n = 6 sites from three mice). **P < 0.01, paired t test. (D) Heat maps showing the locations of an EYFP-expressing control mouse (left) and a ChR2-expressing mouse (right) in a three-chambered social approach task. (E and F) Quantification of time spent by ChR2 mice and EYFP mice in each chamber (top) or zone (bottom) in the first 5-min test (E) and the second 5-min test (F). Error bars indicate means ± SEM (EYFP, n = 9; ChR2, n = 7). *P < 0.05 and ***P < 0.001. Time in chamber or zone: two-way ANOVA and Bonferroni multiple comparison post hoc tests; interaction index: unpaired t test.

  • Fig. 6 Activation of SST INs at low gamma frequency also produces prosocial effect.

    (A) Diagram showing bilateral optogenetic manipulation in freely moving mice. (B) Placement of optic fibers for photostimulation of mPFC SST INs in an SST-Cre mouse bilaterally injected with ChR2-mCherry. Scale bar, 200 μm. (C) Left: Example spectral power of LFP with (blue) and without (black) light stimuli of SST INs at 40 Hz. Shaded areas indicate SEMs. Right: Comparison of relative LFP gamma power between baseline (black) and light stimuli (blue). Error bars indicate means ± SEM (n = 5 sites from three mice). *P < 0.05, paired t test. (D) Heat maps showing the locations of an EYFP-expressing control mouse (left) and a ChR2-expressing mouse (right) in a three-chambered social approach task. (E to F) Quantification of time spent by ChR2 mice and EYFP mice in each chamber (top) or zone (bottom) in the first 5-min test (E) and the second 5-min test (F). Error bars indicate means ± SEM (EYFP, n = 8; ChR2, n = 11), *P < 0.05 and **P < 0.01. Time in chamber or zone: two-way ANOVA and Bonferroni multiple comparison post hoc tests; interaction index: unpaired t test.

Supplementary Materials

  • Supplementary Materials

    Cell type–differential modulation of prefrontal cortical GABAergic interneurons on low gamma rhythm and social interaction

    Ling Liu, Haifeng Xu, Jun Wang, Jie Li, Yuanyuan Tian, Junqiang Zheng, Miao He, Tian-Le Xu, Zhi-Ying Wu, Xiao-Ming Li, Shu-Min Duan, Han Xu

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