Chronic stress disrupts neural coherence between cortico-limbic structures

Abstract

Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC) in rats subjected to short term stress (STS) and chronic unpredictable stress (CUS). CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

Keywords: chronic stress; coherence; hippocampus; power spectrum; prefrontal cortex.

Figure 1

Stressed rats show increased PSD in multiple frequency bands both in the ventral hippocampus and medial PFC. Representative traces of raw data (black line) recorded simultaneously from the vHIP (A) and mPFC (D) of a rat of each group; the red line represents theta filtered component, as example. Power Spectral Density (PSD) values of the vHIP (B) recordings and the mPFC (E) recordings, for controls (CON), short-term stress (STS), and chronic unpredictable stress (CUS); each horizontal line in the Y-axis represents the spectrogram of an individual rat. Group comparison of the PSD values from vHIP (C) and mPFC (F) in the delta (1–4 Hz), theta (4–12 Hz), beta (12–20 Hz), low gamma (20–40 Hz), and high gamma (40–90 Hz) frequency bands. ^*Statistically different from CON, p < 0.05; ^#Statistically different from CUS, p < 0.05; error bars represent SD.

Figure 2

Chronic stress decreases the coherence between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC). (A) Spectral coherence of controls (CON), short term stress (STS), and chronic unpredictable stress (CUS); each horizontal line in the Y-axis represents the spectrogram of an individual rat (B) Group comparison of the coherence values between mPFC and vHIP for delta (1–4 Hz), theta (4–12 Hz), beta (12–20 Hz), low gamma (20–40 Hz), and high gamma (40–90 Hz) frequency bands. ^*Statistically different from CON, p < 0.05; ^#Statistically different from CUS, p < 0.05; error bars represent SD.

Figure 3

Correlations between spectral coherence and power spectral densities in ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC). The graphs present Pearson values for correlations between vHIP-mPFC spectral coherence and vHIP (A,B) or mPFC (C,D) power spectral densities and respective p-values against null hypothesis (corr = 0), for CON and CUS rats (A,C and B,D, respectively). For each brain region, statistically significant correlations are represented in the right panel by color above dark blue (p < 0.05); the direction of the correlation, positive or negative, is given in the left panel by the color code (green to red, positive correlation; green to blue, negative correlation).

Figure 4

CUS-induced changes in PSD and coherence correlate with impairments in cognitive performance. (A,B) Cognitive performance of the studied rats in water maze based tests for spatial reference memory and behavioral flexibility; (A) Learning curves of the reference memory task of control (CON) and chronically stressed (CUS) rats. (B) Average trial time in the new quadrant given as a percentage of the total escape latency for the reversal learning task. (C–F) Analysis of the LFP signals recorded in the vHIP and mPFC of the CON and CUS rats; Power Spectral Density (PSD) values of the vHIP (C) recordings and the mPFC (D) recordings, for controls (CON) and chronically stressed (CUS); (E) Spectral coherence of controls (CON) and chronic unpredictable stress (CUS); in (C–E) each horizontal line in the Y-axis represents the spectrogram of an individual rat; (F) Group comparison of the coherence values between mPFC and vHIP for delta (1–4 Hz), theta (4–12 Hz), beta (12–20 Hz), low gamma (20–40 Hz), and high gamma (40–90 Hz) frequency bands. (G,H) Correlation between behavior and electrophysiological performances of the recorded rats; (G) p-values for Pearson correlations between behavior and electrophysiological performances for each rat; significant correlations highlighted in yellow; (H) Correlation plot for each significant correlation observed in G. ^*Statistically different from CON, p < 0.05; error bars represent SD.

Figure A1

Chronic unpredictable stress decreases synaptic plasticity between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC). (A) Time course of LTP induction after high frequency stimulation (HFS); each circle represents the average of 10 normalized fEPSP slopes with SEM; three groups are depicted: controls (CON, blue), short term stress (STS, green) and chronic unpredictable stress (CUS, red); (inset) representative recordings of fEPSPs pre- and post-HFS (scale bar: 1 mV; 5 ms) of a CON rat; (B) Normalized values of LTP averaged for the three groups of rats: CON, STS, and CUS; ^*statistically different from controls, p < 0.05; error bars represent SD.

Figure A2

Chronic stress exposure does not induce locomotor deficits. Average swimming speeds of CON (blue) and CUS (red) rats during the 4 days spatial reference memory task. No differences are observed between groups in each day (p > 0.05); error bars represent SD.

Figure A3

Stressed rats show increased PSD in multiple frequency bands both in the ventral hippocampus and medial PFC in the second set of rats. Group comparison of the power spectral density (PSD) values from vHIP (A) and mPFC (B) in the delta (1–4 Hz), theta (4–12 Hz), beta (12–20 Hz), low gamma (20–40 Hz) and high gamma (40–90 Hz) frequency bands. ^*Statistically different from CON, p < 0.05; error bars represent SD.

Figure A4

Identification of electrode recording sites. Left panel, recording site location in control (CON, blue), short term stress (STS, green) and chronic unpredictable stress (CUS, red) rats, within the medial prefrontal cortex (A, mPFC) and ventral hippocampus (B, vHIP); Images adapted from Paxinos and Watson, . Right panel, Cresyl Violet stained 50 μm sections with an electrolytic lesion at the recording site.