Subhypnotic doses of propofol impair spatial memory retrieval in rats

Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β（GSK-3β） activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task（eight acquisition trials in one session） and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol（25 mg/kg） spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.

VGLUT3 neurons in median raphe control the efficacy of spatial memory retrieval via ETV4 regulation of VGLUT3 transcription

The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons(PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease(AD mice),VGLUT3→PGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3→PGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.

The differential requirement of mushroom body α/β subdivisions in long-term memory retrieval in Drosophila

The mushroom body(MB),a bilateral brain structure pos-sessing about 2000-2500 neurons per hemisphere,plays a central role in olfactory learning and memory in Dros-ophila melanogaster.Extensive studies have demonstrat-ed that three major types of MB neurons(α/β,α’/β’andγ)exhibit distinct functions in memory processing,including the critical role of approximately 1000 MBα/βneurons in retrieving long-term memory.Inspired by recent fi ndings that MBα/βneurons can be further divided into three subdivisions(surface,posterior and core)and wherein theα/βcore neurons play an permissive role in long-term memory consolidation,we examined the functional differ-ences of all the three morphological subdivisions of MBα/βby temporally precise manipulation of their synaptic outputs during long-term memory retrieval.We found the normal neurotransmission from a combination of MBα/βsurface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory,whereas output from MBα/βposterior or core subdivision alone is dispensable.These results imply a specifi c requirement of about 500 MBα/βneurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MBα/βregion.

Optogenetics and its application in neural degeneration and regeneration

Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.

Effects of immune activation on the retrieval of spatial memory

Objective It has been shown that there are extensive interactions between the central nervous system and the immune system.The present study focused on the effects of lipopolysaccharide（LPS）on memory retrieval,to explore the interaction between immune activation and memory.Methods C57BL/6J mice（8 weeks old）were first trained in the Morris water maze to reach asymptotic performance.Then mice were tested 24 h after the last training session and LPS was administered（1.25 mg/kg,i.p.）4 h prior to the testing.The retrieval of spatial memory was tested by probe trial,and the time spent in the target quadrant and the number of platform location crosses were recorded.ELISA was performed to detect interleukin-1β（IL-1β）protein level in the hippocampus of mice tested in the water maze.Results Although LPS induced overt sickness behavior and a significant increase in the level of IL-1β in the hippocampus of mice,there was no significant difference in the time spent in the target quadrant or in the number of platform location crosses between LPS-treated and control groups in the probe trial testing.Conclusion Immune activation induced by LPS does not impair the retrieval of spatial memory.

A hippocampus-inspired illumination time-resolved device for neural coding

Artificial photonic synapses have set off a new upsurge for mimicking a series of neural activities in recent years.In particular,the investigation of learning and memory behaviors with pressure or emotion and corresponding mechanisms is currently the focus of more attention.Herein,a hippocampus-inspired device based on MoS_(2) for illumination time encoding is fabricated,in which the encryption technology is employed for data security.In addition,the pressureinduced memory behaviors with full memory function(memory trace)over time such as encoding,storage and retrieval are demonstrated,resulting from the decreasing positive photocurrent of the MoS;devices.The proposed mechanism of the memory effect when exposed to the light is elucidated in detail.Moreover,the effect of stress hormone on memory behavior is displayed via different illumination time periods and light intensities.These results indicate the potential application of MoS_(2) devices in artificial neural network.