Directional prefrontal-thalamic information flow is selectively required during spatial working memory retrieval

Abstract

Introduction: Spatial working memory is a kind of short-term memory that allows temporarily storing and manipulating spatial information. Evidence suggests that spatial working memory is processed through three distinctive phases: Encoding, maintenance, and retrieval. Though the medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) are involved in memory retrieval, how the functional interactions and information transfer between mPFC and MD remains largely unclear.

Methods: We recorded local field potentials (LFPs) from mPFC and MD while mice performed a spatial working memory task in T-maze. The temporal dynamics of functional interactions and bidirectional information flow between mPFC and MD was quantitatively assessed by using directed transfer function.

Results: Our results showed a significantly elevated information flow from mPFC to MD, varied in time and frequency (theta in particular), accompanying successful memory retrieval.

Discussion: Elevated theta information flow, a feature that was absent on error trials, indicates an important role of the directional information transfer from mPFC to MD for memory retrieval.

Keywords: information flow; local field potentials (LFPs); medial prefrontal cortex (mPFC); mediodorsal thalamus (MD); spatial working memory.

FIGURE 1

Behavioral task and oscillatory dynamics in mPFC and MD during the task. (A) Schema of a single trial of the DNMTP task in T-maze. In the sample/choice phase, the mouse’s initial position was defined as the point a/d, and the turn began was denoted as the point b/e, and the reward position was denoted as the point c/f. (B) Behavioral performance. The percentage of correct goal choice was enhanced as training progressed n = 8 mice. Error bars represent mean ± SEM. (C) Diagram for simultaneous multi-channel microelectrode recording. (D) Histological verification of the recording sites in the mPFC, PrL region (left) and MD (right). The partial brain sections show the typical recording sites (marked by rectangle) in the two regions. The superimposed schematics adapted from Paxinos and Charles (2005) show the coronal brain sections at 1.78 mm anterior and 1.22 mm posterior to the bregma. Scale bar, 500 μm. (E) Time-frequency power spectrum of LFPs during the choice phase on correct trials. (Left) Example single-trial LFP traces recorded from mPFC (purple) and MD (green). (Right) LFP power spectrum cross correct trials in mPFC and MD for a single mouse. (F) Same as (E), but for sample phase.

FIGURE 2

Theta-band information flow from mPFC to MD is prominent during the choice phase. (A) The average information flow across different frequencies during the choice phase. (Left) Information flow as a function of frequency across subjects (n = 8 mice). The red and blue curves represent the information flow on correct and incorrect trials, respectively. (Right) Comparison of information flow across different frequencies on correct and incorrect trials (correct: two-way AONVA, F = 55.02, P < 0.001; incorrect: two-way ANOVA, P > 0.05). (B) Same as (A), but for the sample phase (correct: two-way AONVA, P > 0.05; incorrect: two-way ANOVA, P > 0.05). (C) Running speed and duration on correct and incorrect trials showed no significant difference (Mann–Whitney test, speed: P > 0.05; duration: P > 0.05). (D) Running speed and duration between the choice and sample phases showed no significant difference (Mann–Whitney test, speed: P > 0.05; duration: P > 0.05). ***P < 0.001, ns, not significant.

FIGURE 3

Enhanced theta-band information flow from mPFC to MD correlates with the task epochs. (A) The average theta-band information flow from mPFC to MD during the choice phase across subjects (n = 8 mice). (left) Changes in information flow over position [from start box (location “d”) to arrival at the reward port (location “f”)]. (Right) Comparison of theta-band information flow on correct, incorrect trials and rest stage (two-way ANOVA, F = 312.9, P < 0.001). (B) Theta-band information flow shows a remarkably increase on correct trials [ΔIF_mPFC→MD is defined as peak of IF (the maximum of IF during the choice period: d→e) minus the initial value of IF (at location “d”)]. Correct: two-way AONVA, F = 43.31, P < 0.001; incorrect: two-way ANOVA, P > 0.05. (C) same as (A), but for sample phase. The information flow showed no difference in the different trial types and the values on correct and incorrect trials were apparently higher than that at rest stage (two-way ANOVA, F = 274.8, P < 0.001). (D) Same as (B), but for sample phase [ΔIF_mPFC→MD is defined as peak of IF (the maximum of IF during the sample period: a→b) minus the initial value of IF (at location “a”)]. Correct: two-way AONVA, F = 12.13, P < 0.001; incorrect: two-way ANOVA, F = 44.29, P < 0.001. *P < 0.05, **P < 0.01, and ***P < 0.001. ns, not significant.

FIGURE 4

Directional information flow from mPFC to MD is distinct during the choice phase. (A) The bidirectional information flow between mPFC and MD across subjects (n = 8 mice) during the choice phase on correctly performed trials. (Left) The red and green curve represents the information flow from mPFC to MD and from MD to mPFC, respectively. (Right) The information flow from mPFC to MD was significantly higher than the reverse (Mann–Whitney test: P < 0.001). (B) Same as (A), but for sample (Mann–Whitney test: P > 0.05). ***P < 0.001, ns, not significant.