Circadian modulation of memory and plasticity gene products in a diurnal species

Abstract

Cognition is modulated by circadian rhythms, in both nocturnal and diurnal species. Rhythms of clock gene expression occur in brain regions that are outside the master circadian oscillator of the suprachiasmatic nucleus and that control cognitive functions, perhaps by regulating the expression neural-plasticity genes such as brain derived neurotrophic factor (BDNF) and its high affinity receptor, tyrosine kinase B (TrkB). In the diurnal grass rat (Arvicanthis niloticus), the hippocampus shows rhythms of clock genes that are 180° out of phase with those of nocturnal rodents. Here, we examined the hypothesis that this reversal extends to the optimal phase for learning a hippocampal-dependent task and to the phase of hippocampal rhythms in BDNF/TrkB expression. We used the Morris water maze (MWM) to test for time of day differences in reference memory and monitored daily patterns of hippocampal BDNF/TrkB expression in grass rats. Grass rats showed superior long-term retention of the MWM, when the training and testing occurred during the day as compared to the night, at a time when nocturnal laboratory rats show superior retention; acquisition of the MWM was not affected by time of day. BDNF/TrkB expression was rhythmic in the hippocampus of grass rats, and the phase of the rhythms was reversed compared to that of nocturnal rodents. Our findings provide correlational evidence for the claim that the circadian regulation of cognition may involve rhythms of BDNF/TrkB expression in the hippocampus and that their phase may contribute to species differences in the optimal phase for learning.

Keywords: BDNF/TrkB; Circadian rhythm; Cognition; Hippocampus; Morris water maze; Plasticity genes.

Figure 1. Time of training effects during acquisition trials

Cochran's Q analyses showed a significant effect of training days for both trial 1 data (panel A; AM group: Q(5)=31.957 and PM group: Q(5)=14.412, ps < .001) and trials 1-4 averaged data showing the averaged data (+ SEM) for each day (panel B; AM group: Q(5)=69.985, and PM group: Q(5)=60.255, p <.001), but Chi squared analysis showed no effect of time of training on proportion of grass rats to find the platform each day for both data sets (χ2_(1,N=24) = 0.00-3.227, all Ps> 0.07). The SEM values in panel B are so small that they are obscured by the symbols demarking the value of each data point.

Figure 2. Differential effects of time of training on acquisition and retention probe test performance

Chi squared analyses revealed that although there was no effect of ZT on the proportion of grass rats to find the platform during the acquisition probe, (χ2 _{(1, N=24)} = .202, P> 0.05) (panel A), during the retention probe (panel B) there was an effect of ZT (χ2 _{(1, N=24)} =10.667, P< 0.001).

Figure 3. Time of day effects on retention probe

There was a significant effect of time of training on all measures except swim velocity, (t₍₂₂₎ =.256, P > 0.05) during the retention probe. Significant time of training effects were seen in swim path, (t ₍₂₂₎ =50.30, P < 0.001) and latency to platform quadrant, ( t ₍₂₂₎ =9.602, P < 0.001). AM trained grass rats were faster to the platform quadrant and had shorter swim paths than PM trained grass rats. Bar charts showing the mean (+ SEM) inches (swim path, upper left), inches/second (swim velocity, upper right) and seconds (latency to platform quadrant, lower left). Chi squared analysis revealed a significant effect of training time on the proportion of grass rats to engage in thigmotaxis (χ2_(1,N=24) = 6.171, P< 0.01). Fewer AM trained grass rats engaged in thigmotaxic behavior than PM trained grass rats. Significant differences between AM and PM groups are denoted by asterisks.

Figure 4. Rhythms in Plasticity gene products

Left Panels: Sampling boxes (rectangles) were used for cell counts in of the CA1, dorsal blades of the DG, and hilus as described in Materials and Methods. Anatomical boundaries are based on Paxinos and Watson (1997). CA1, DG, dentate gyrus; ZT, Zeitgeber Time. Center and Right Panels: Photomicrographs depicting BDNF and Trk B expression at two different ZTs. Scale bar represent 200μm. Line charts showing the mean (+ SEM) number of BDNF (Center) and TrkB (Right) expressing cells for each ZT in the CA1, dorsal blade of the DG, and hilus of male grass rats. Significant differences between ZTs (p<0.001) are noted by different letters. Grey region on each chart indicates the dark phase of the cycle.