Gong-Wu Wang

NR2A and NR2B are the major GluR2 subunits of N-methyl-D-aspartate (NMDA) receptor. NR2B-containing NMDA receptor was found to be exclusively expressed in post-synapses in layer III pyramidal cells of the prefrontal cortex (PFC). Many studies have suggested the importance of PFC NR2B-containing NMDA receptor for working memory, especially for the persistent delay cell firing. However, direct evidence for the necessity of PFC NR2B-containing NMDA receptor on working memory is still absent, especially in non-human primates. Here, we directly evaluated the necessity of PFC synaptic NR2B for working memory in both rats and monkeys. We first examined the synaptosome expression ratio of NR2B/2A in the PFC, hippocampus and visual cortex, and confirmed a relatively higher expression ratio of NR2B/2A in the PFC than in the hippocampus and visual cortex in both species. We then investigated the effects of intra-PFC blockade of NR2B on the performance of spatial working memory and pattern discrimination, and found that the spatial working memory, but not pattern discrimination, was robustly impaired in a delay length-dependent way in both species. The present study provided behavioral and neuropharmacological evidence for the critical role of PFC NR2B-containing receptors in working memory performance in non-human primates.

The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH–BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH–BLA circuit in IA memory consolidation. Male Wistar rats with implanted guide cannulae were trained with a one-trial IA task, then received immediate intracerebral injections of muscimol or saline, and were tested 24 h later. Muscimol injection into the bilateral BLA, or the unilateral VH and contralateral BLA, but not the unilateral VH and ipsilateral BLA, significantly decreased the retention latencies (versus saline treatment). The results suggest that the VH–BLA circuit could be an important circuit to modulate consolidation of IA memory in rats.

In this study, one-trial step-through task was applied to reveal the effect of prefrontal infralimbic cortex GABAA receptor agitating on passive avoidance memory consolidation in rats. Immediately after training (with shock), GABAA receptor agonist, muscimol (0.5 μg/0.25 μL) or saline (0.25 μL) was infused into the test animal's infralimbic cortex, then, the latencies of rats stepping through the dark room were recorded. Meanwhile, local EEG power was adopted as index of the inactivation effect of muscimol. The step-through latencies of muscimol group were comparable(P>0.05)with saline group, but their local EEG power had decreased significantly (P<0.05). These results suggest that the inactivation of infralimbic cortex would not demolish the passive avoidance memory consolidation of rats.

Present work investigated the effects of tail suspension stress (TSS) on spatial memory acquisition, consolidation, and its reversal learning in mice. Eighty-one adult male KM mice were divided into four groups (each group including a TSS subgroup and its control subgroup): absolute spatial memory acquisition and consolidation groups (group AA and CA); relative spatial memory acquisition and consolidation groups (group AR and CR). TSS (20 min) was performed immediately before (acquisition) or after (consolidation) a daily training. Results showed that there was no significant difference between control animals and TSS animals in each group in early spatial memory training days (5-8 d of training). Along with training, the performance of control animals improved significantly, but the performance of TSS animals improved slightly (group AA, CA and AR) or even did not change (group CR) (P<0.01). Reversal learning was also impaired in TSS animals (P<0.01). The results indicated that TSS could impair spatial memory acquisition, consolidation and reversal learning (especially the relative spatial memory consolidation and its reversal learning) in mice.

Although prefrontal and hippocampal neurons are critical for spatial working memory, the function of glial cells in spatial working memory remains uncertain. In this study we investigated the function of glial cells in rats’ working memory. The glial cells of rat brain were inhibited by intracerebroventricular (icv) injection of fluorocitrate (FC). The effects of FC on the glial cells were examined by using electroencephalogram (EEG) recordings and delayed spatial alternation tasks. After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC, the EEG power spectrum recorded from the hippocampus increased, but the power spectrum for the prefrontal cortex did not change, and working memory was unaffected. Following an icv injection of 10 μL of 20 nmol/L FC, the EEG power spectra in both the prefrontal cortex and the hippocampus increased, and working memory improved. The icv injection of 10 μL of 50 nmol/L FC, the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased, and working memory was impaired. These results suggest that spatial working memory is affected by centrally administered FC, but only if there are changes in the EEG power spectrum in the prefrontal cortex. Presumably, the prefrontal glial cells relate to the working memory.