Figure 1.
Electrophysiological recordings in rats performing the T-maze Task.
A) Schematic of the T-Maze. On each trial, animals were placed in the start box (red) by the experimenter for a delay interval. The retaining gate was removed and the animal traveled to the branch point and revealed the choice to enter either arm (grey). Reward was then offered by the experimenter within the reward zone (cyan) if the arm opposite to the spatial location of last arm entered was chosen. Following reward or an incorrect choice, the animal was picked up by the experimenter and returned to the start box for a subsequent trial. Inset illustrates the video tracked path of a rat during one recording session. NOTE: paths crossing the T-maze from Pickup to Start Box reflect relocating the animal by the experimenter (right handed). B) Bar graph quantifying performance in the T-maze task during baseline and acute noise stress (93 db) conditions. n = 5; **p<0.01. C) 40× photomicrograph illustrating the final placement of one of eight microwires in layer V of the plPFC (Arrow Tip; CC, corpus callosum; plPFC, prelimbic PFC). D) Action potential waveforms of 5 discriminated and validated plPFC neurons. Waveform width = 450 µs. Waveforms from these units exhibited separable clusters when plotted in principal component space (inset). Sorted spiking activity with unsorted activity is presented in Fig. S1. The cyan colored neuron represents the characteristic WS-type neuron. E) Timeline of behavioral training and testing. Details of a single testing day are shown beginning at 8:00 AM.
Figure 2.
Peri-stimulus time histograms (PSTHs) illustrate the effects of stress on plPFC neuron task-related spiking activity.
A) T-maze schematic and associated peri-event raster and histogram analysis illustrates prototypic (i) delay- (ii) run- (iii) branch- (iv) choice- (v) reward- and (vi) pickup-related activity observed from plPFC neurons (0 sec. = start of respective behavioral interval; n = 40 correct trials of a baseline recording session; Delay length = 20 sec.; 5 msec. bins). Colored fiduciaries indicate beginning of each major event of the T-maze task (Red, Start Box; Green, Gate; Magenta, Branch; Grey, Choice; Cyan, Reward; Yellow, Pickup). B) Task-related discharge of a single WS-type plPFC neuron during correctly executed trials with a left arm entry during the baseline recording session (17 trials; top) and subsequent stress session (11 trials; bottom). Delay-related spiking of this delay neuron was enhanced during stress. Inset illustrates recorded spike waveforms. PSTH y-axis represents spiking probability/bin normalizing for different numbers of trials (5 msec. bins). C) Run-related activity suppressed during stress conditions. D) Suppression of choice-related activity during stress. Labeling conventions of C–D are identical to B.
Figure 3.
Effects of stress on task-related discharge rates of plPFC neurons.
Average discharge rates of WS-type plPFC neurons during stress conditions were quantified for each behavioral interval of correct trials and plotted as a percent change from baseline conditions (1st recording session) for matched behavioral intervals trials with identical T-maze arm choices. Box and whisker plots illustrate that during stress, discharge rates within the Delay, Reward, and Pickup behavioral intervals are increased. During the Run and Branch behavioral intervals, discharge rates are suppressed under stress conditions. Colored box and whiskers designate the first and fourth quartiles and median line (box), distribution mean (dot), and 5–95% range of the data (whiskers). (**p<0.01 FDR corrected T-Test compared to baseline).
Figure 4.
Stress-related changes in plPFC neuron spike-history predicted discharge (SHPD) throughout baseline or acute stress conditions.
A) Spiking gain (rate-ratio expα,η) measures of the contribution of spike history at different points back in time for a small (n = 50) ensemble of neurons. The SHPD gain of one exemplar neuron is highlighted. B) SHPD gain at different points back in time decay exponentially under baseline and stress conditions (Model 1a). Described in the main text, stress produced an overall reduction in SHPD gains (inset; *p<0.005), but did not significantly alter the decay of gains at any spike history time bin. C) Schematic of recurrent pathways within the PFC of connectivity within layers II/III or V as well as connectivity between II/III and V represents one putative mechanism supporting SHPD. Adopted from: [72]–[74].
Figure 5.
Stress-related changes in delay- and response-related plPFC neuron spike-history predicted discharge (SHPD).
A) Delay-specific gains of SHPD interaction terms from the CI-GLM (Model 2; α, η) were averaged across plPFC neurons and plotted. B) Response interval-specific gains of SHPD interaction terms (Model 3). Stress suppressed delay-specific SHPD gains and increased the impact of the most recent spiking history during the response period. (*p<0.05 FDR corrected compared to baseline; x<0.05 FDR corrected compared to 1.0).
Figure 6.
Characterization of generalized linear models of task-related activity.
Plot of 80 seconds of spike train data, spanning three trials and fit with a GLM using (A) a homogeneous Poisson model, (B) an inhomogeneous Poisson model, and (C) an a conditional intensity model (Model 1b, during baseline conditions only). Spike counts of the original spike train are plotted with black dots against lambda (λ; green line with red confidence intervals). X-axis = experimental time. D) Kolmogorov–Smirnov (K-S) goodness-of-fit plot demonstrates that incorporation of spike history improves performance of the CI-GLM (blue vs. green line). The K-S plot of the final model (blue line; model from panel C) falls within equivalency confidence intervals of the K-S test (diagonal solid and dotted lines) for all quantiles, indicating that inclusion of spike history with behavioral intervals in the CI-GLM is critical to appropriately model plPFC spiking activity. Inhomogeneous Poisson models using solely the behavioral states of the task overestimate neuron interspike intervals (green line; model from panel B). Models of neuronal activity (1–3; main text) also passed K-S goodness-of-fit tests (Fig. S3).