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Cue-inhibited ventrolateral periaqueductal gray neurons signal fear output and threat probability in male rats

  1. Kristina M Wright  Is a corresponding author
  2. Thomas C Jhou
  3. Daniel Pimpinelli
  4. Michael A McDannald  Is a corresponding author
  1. Boston College, United States
  2. Medical University of South Carolina, United States
Research Advance
Cite this article as: eLife 2019;8:e50054 doi: 10.7554/eLife.50054
4 figures, 1 table, 1 data set and 1 additional file

Figures

Fear discrimination, histology, heat plot and waveform characteristics.

(A) Pavlovian fear discrimination consisted of three cues predicting unique foot shock probabilities: danger, p = 1.00 (red); uncertainty, p = 0.375 (purple); and safety, p = 0.00 (blue). (B) Microelectrode bundle placements for all rats (n = 6) and all neurons (n = 245) during recording sessions are represented by salmon bars. (C) Mean + individual (data points) suppression ratio for danger, uncertainty, and safety is shown for all recording sessions (n = 88). (D) Normalized firing rate in 1 s intervals is shown for each Flip (n = 45, top) and Sustain (n = 46, bottom) neuron for each trial type (danger, uncertainty and safety). Color scale for normalized firing rate is shown to the right; red indicates high firing and blue low firing. Cue onset and offset are indicated. Single-unit waveform properties of Flip (sea foam) and Sustain (periwinkle) neurons are shown: (E) baseline firing rate, (F) half the duration, and (G) amplitude ratio. +95% bootstrap confidence interval for differential suppression ratio does not contain zero.

https://doi.org/10.7554/eLife.50054.002
Figure 2 with 1 supplement
vlPAG neurons flip to excitation or sustain inhibition over cue presentation.

(A) Mean normalized firing to danger (red), uncertainty (purple) and safety (blue) is shown for the 2 s pre-cue period, 10 s cue period, and 2 s delay period for the Flip population (n = 45). Cue onset (On) and offset (Off) are indicated by vertical black lines. (B) Mean (bar) and individual (data points), normalized firing for Flip neurons during the first 5 s of cue presentation (Early, left) and the last 5 s of cue presentation (Late, right) is shown for each cue. (C) Mean normalized firing for the Sustain population (n = 45), shown as in A. (D) Mean and individual (data points), normalized firing for Sustain neurons, as in B. +95% bootstrap confidence interval for differential firing does not contain zero. #95% bootstrap confidence interval for normalized firing does not contain zero.

https://doi.org/10.7554/eLife.50054.003
Figure 2—figure supplement 1
Trial by trial firing for Flip and Sustain populations.

(A, left ) Normalized firing rate for the Flip population (n = 45) is shown across cue presentation for each of the six danger trials. Trials are color-coded from dark (first trial) to light (last trial) with ‘On’ indicating cue onset and ‘Off’ indicating cue offset. (A, center) Mean population firing rate for the first 5 s of cue presentation (early) is shown for each trial. Color scheme maintained from A, left. Mean population baseline firing rate (2 s prior to cue presentation) is shown for each trial (gray). (A, right) Firing for the last 5 s of cue presentation (late) shown as in A, center. Identical figures using unique color schemes were made for each trial type: (B) uncertainty shock, (C) uncertainty omission and (D) safety. An identical set of figures were made for the Sustain population (n = 46; E–H).

https://doi.org/10.7554/eLife.50054.004
Sustain and Flip populations signal threat probability and fear output.

(A) Mean ± SEM beta coefficients are shown for each regressor (probability: pink, fear output: green), in 1 s intervals, for the Flip population (n = 46). (B) Beta coefficients during the first, 5 s of cue presentation (Early) for fear output and threat probability are plotted for all Flip neurons. Black dashed trendline, the square of Pearson’s correlation coefficient (R2) with associated p value, and sign test p value demonstrating regressor bias shown. Background shading indicates negative beta coefficients, color coded by regressor. (C) Beta coefficients during the last, 5 s of cue presentation (Late) for fear output and threat probability are plotted for all Flip neurons. (D) Mean ± SEM beta coefficients are shown for each regressor for the Sustain population (n = 46). All graph properties maintained from A. (E) Beta coefficients during Early cue presentation for fear output and threat probability are plotted for all Sustain neurons. All graph properties maintained from B. (F) Beta coefficients during Late cue presentation for fear output and threat probability are plotted for all Sustain neurons. #95% bootstrap confidence interval for beta coefficient does not contain zero.

https://doi.org/10.7554/eLife.50054.005
Sustain and Flip populations probability tuning.

(A) Mean beta coefficient for probability is shown for early (light pink) or late (hot pink) cue presentation for each of nine uncertainty assignments for the Flip population (n = 45). The peak or trough of each curve is indicated by a single point with the corresponding uncertainty assignment highlighted in the same color on the x axis below. Black dashed line indicates the actual foot shock probability associated with uncertainty (p = 0.375). Green dashed line indicates the mean proportional distance of uncertainty between danger and safety (suppression ratio). The blue-to-red color bar at the top of the figure demonstrates that a leftward shift along the x-axis reflects an uncertainty assignment similar in quality to safety (p = 0.000) versus those that would be more similar to a danger cue on the far right (p = 1.000). (B) All graph properties maintained from A, but applied to the Sustain population.

https://doi.org/10.7554/eLife.50054.006

Tables

Key resources table
Reagent type
(species) or
resource
DesignationSource or
Reference
IdentifierAdditional
information
AntibodyAnti-Tryptophan Hydroxylase (sheep polyclonal)SigmaCat # T8575
RRID:AB_1080792
[1:1000] in 0.05M PBS
AntibodyBiotinylated Anti-Sheep (rabbit clonality unknown)Vector LabsCat # PK-6106
RRID:AB_2336217
[1:200] in 0.05M PBS
Chemical Compound, DrugNormal Rabbit SerumVector LabsCat # PK-6106
RRID:AB_2336825
1% in 0.05M PBS
Chemical Compound, DrugAvidinVector LabsCat # PK-6106
RRID:AB_2336825
[1:200] in 0.05M PBS
Chemical Compound, DrugBiotinVector LabsCat # PK-6106
RRID:AB_2336825
[1:200] in 0.05M PBS
Chemical Compound, DrugNovaRED Perioxidase (HRP) Substrate KitVector LabsCat # SK-4800
RRID: AB_2336845
18 drops (1), 12 drops (2), 12 drops (3) and 12 drops H2O2 solution in DI H2O.
Chemical Compound, DrugTritonSigmaCat # T8787
Chemical Compound, DrugHydrogen PeroxideSigmaCat # 216763
Chemical Compound, DrugParaformaldehydeSigmaCat # P6148
Chemical Compound, DrugSucroseFisher ScientificCat # S5
Chemical Compound, DrugSodium ChlorideFisher ScientificCat # S 640
Chemical Compound, DrugHistoprep 100% Reagent AlcoholFisher ScientificCat # HC800
Chemical Compound, DrugHistoprep 95% Reagent AlcoholFisher ScientificCat # HC1300
Chemical Compound, DrugHistoclear IIFisher ScientificCat # 5089990150
Chemical Compound, DrugOmnimountFisher ScientificCat # 5089990146
Chemical Compound, Drug10% Neutral Buffered FormalinFisher ScientificCat # 22899402
Chemical Compound, DrugPotassium Phosphate MonobasicFisher ScientificCat # P285
Chemical Compound, DrugPotassium Phosphate DibasicFisher ScientificCat # P288
Software and AlgorithmsMED PC-IVMed AssociatesRRID:SCR_012156
Software and AlgorithmsOmniPlexPlexonData Acquisition System
Software and AlgorithmsOffline Sorter V6PlexonRRID:SCR_000012
Software and AlgorithmsNeuroExplorerPlexonRRID:SCR_001818
Software and AlgorithmsMatlabMathworksRRID:SCR_001622
Software and AlgorithmsStatisticaStatSoftRRID:SCR_014213
Software and AlgorithmsSPSSIBMRRID:SCR_002865
Software and AlgorithmsAdobe IllustratorAdobeRRID:SCR_010279
Software and AlgorithmsAdobe PhotoshopAdobeRRID:SCR_014199
OtherPlexon standard commutatorPlexonCat # 50122
OtherPlexon head stage cablePlexonCat # 91809–017Metal Mesh Enclosed Cable
OtherPlexon head stagePlexonCat # 40684–020
OtherOmnetics connectorOmnetics CorporationCat # A79042-001
OtherGreen board - Moveable ArraySan Francisco CircuitsCat # PCB
OtherStainless Steel ground wireAM SystemsCat # 791400
OtherFormvar Insulated Nichrome WireAM SystemsCat # 761500
OtherDustless Precision PelletsBio-ServCat # F0021

Data availability

Data have been deposited at: http://crcns.org/data-sets/bst/pag-1.

The following previously published data sets were used
  1. 1
    Collaborative Research in Computational Neuroscience
    1. KM Wright
    2. MA McDannald
    (2019)
    Ventrolateral periaqueductal gray single-single unit activity during multi-cue fear discrimination in rats.

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