Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval

The amygdalohippocampal circuit plays a pivotal role in Pavlovian fear memory. We simultaneously recorded electrical activity in the lateral amygdala (LA) and the CA1 area of the hippocampus in freely behaving fear-conditioned mice. Patterns of activity were related to fear behavior evoked by conditioned and indifferent sensory stimuli and contexts. Rhythmically synchronized activity at theta frequencies increased between the LA and the CA1 after fear conditioning and became significant during confrontation with conditioned fear stimuli and expression of freezing behavior. Synchronization of theta activities in the amygdalohippocampal network represents a neuronal correlate of conditioned fear, apt to improve neuronal communication during memory retrieval.     

Reduction of theta rhythm dissociates grid cell spatial periodicity from directional tuning

Grid cells recorded in the medial entorhinal cortex of freely moving rats exhibit firing at regular spatial locations and temporal modulation with theta rhythm oscillations (4 to 11 hertz). We analyzed grid cell spatial coding during reduction of network theta rhythm oscillations caused by medial septum (MS) inactivation with muscimol. During MS inactivation, grid cells lost their spatial periodicity, whereas head-direction cells maintained their selectivity. Conjunctive grid-by-head-direction cells lost grid cell spatial periodicity but retained head-direction specificity. All cells showed reduced rhythmicity in autocorrelations and cross-correlations. This supports the hypothesis that spatial coding by grid cells requires theta oscillations, and dissociates the mechanisms underlying the generation of entorhinal grid cell periodicity and head-direction selectivity.     

Awake hippocampal sharp-wave ripples support spatial memory

The hippocampus is critical for spatial learning and memory. Hippocampal neurons in awake animals exhibit place field activity that encodes current location, as well as sharp-wave ripple (SWR) activity during which representations based on past experiences are often replayed. The relationship between these patterns of activity and the memory functions of the hippocampus is poorly understood. We interrupted awake SWRs in animals learning a spatial alternation task. We observed a specific learning and performance deficit that persisted throughout training. This deficit was associated with awake SWR activity, as SWR interruption left place field activity and post-experience SWR reactivation intact. These results provide a link between awake SWRs and hippocampal memory processes, which suggests that awake replay of memory-related information during SWRs supports learning and memory-guided decision-making.     

Independent codes for spatial and episodic memory in hippocampal neuronal ensembles

Hippocampal neurons were recorded under conditions in which the recording chamber was varied but its location remained unchanged versus conditions in which an identical chamber was encountered in different places. Two forms of neuronal pattern separation occurred. In the variable cue-constant place condition, the firing rates of active cells varied, often over more than an order of magnitude, whereas the location of firing remained constant. In the variable place-constant cue condition, both location and rates changed, so that population vectors for a given location in the chamber were statistically independent. These independent encoding schemes may enable simultaneous representation of spatial and episodic memory information.     

Theta rhythm: a temporal correlate of memory storage processes in the rat

We examined the amount of theta rhythm (4 to 9 hertz) in cortical electroencephalograms of rats for 30 minutes after training in one-trial tasks. Some animals received electroconvulsive shock after training. The amount of theta in the electroencephalogram after training was positively correlated with the degree of subsequent retention of a footshock, whether animals had received electroconvulsive shock or not.     

Operant control of occipital theta rhythm affects performance in a radar monitoring task

Detection efficiency of human observers deteriorates rapidly in monotonous monitoring tasks; this effect (the vigilance decrement) has been associated with increased theta band activity in the electroencephalogram. Suppression of theta activity by operant methods enhances monitoring efficiency, whereas theta augmentation further degrades task performance. These results demonstrate a lawful relationship between operantly regulated cortical activity and behavior in man.     

Intellectual deficit associated with transplacentally induced microcephaly in the rat

Fischer rats injected with methylazoxymethanol late in pregnancy produce young with considerably reduced cerebral hemispheres. They appear normal otherwise. As adults these animals make many more errors in the Hebb-Williams maze than do control animals.     

Lactate-supported synaptic function in the rat hippocampal slice preparation

The present study was undertaken to examine the possibility that cerebral energy metabolism can be fueled by lactate. As a sole energy substrate, lactate supported normal synaptic function in rat hippocampal slices for hours without any sign of deterioration. Slices that were synaptically silent as a result of glucose depletion could be reactivated with lactate to show normal synaptic function. When slices were exposed to the glycolytic inhibitor iodoacetic acid, lactate-supported synaptic function was unaffected, whereas that supported by glucose was completely abolished. This indicated that lactate was metabolized directly via pyruvate to enter the tricarboxylic acid cycle. Thus, under conditions that lead to lactate accumulation (cerebral ischemia) this "end product" may be a useful alternative as a substrate for energy metabolism.     

The spatial periodicity of grid cells is not sustained during reduced theta oscillations

Grid cells in parahippocampal cortices fire at vertices of a periodic triangular grid that spans the entire recording environment. Such precise neural computations in space have been proposed to emerge from equally precise temporal oscillations within cells or within the local neural circuitry. We found that grid-like firing patterns in the entorhinal cortex vanished when theta oscillations were reduced after intraseptal lidocaine infusions in rats. Other spatially modulated cells in the same cortical region and place cells in the hippocampus retained their spatial firing patterns to a larger extent during these periods without well-organized oscillatory neuronal activity. Precisely timed neural activity within single cells or local networks is thus required for periodic spatial firing but not for single place fields.     

Requirement for hippocampal CA3 NMDA receptors in associative memory recall

Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which the N-methyl-D-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice. The mutant mice normally acquired and retrieved spatial reference memory in the Morris water maze, but they were impaired in retrieving this memory when presented with a fraction of the original cues. Similarly, hippocampal CA1 pyramidal cells in mutant mice displayed normal place-related activity in a full-cue environment but showed a reduction in activity upon partial cue removal. These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall.     

Sites of neocortical reorganization critical for remote spatial memory

The hippocampus is crucial for spatial memory formation, yet it does not store long-lasting memories. By combining functional brain imaging and region-specific neuronal inactivation in mice, we identified prefrontal and anterior cingulate cortices as critical for storage and retrieval of remote spatial memories [correction]. Imaging of activity-dependent genes also revealed an involvement of parietal and retrosplenial cortices during consolidation of remote memory. Long-term memory storage within some of these neocortical regions was accompanied by structural changes including synaptogenesis and laminar reorganization, concomitant with a functional disengagement of the hippocampus and posterior cingulate cortex [correction]. Thus, consolidation of spatial memory requires a time-dependent hippocampal-cortical dialogue, ultimately enabling widespread cortical networks to mediate effortful recall and use of cortically stored remote memories independently.     

Loss of a callose synthase results in salicylic acid-dependent disease resistance

Plants attacked by pathogens rapidly deposit callose, a beta-1,3-glucan, at wound sites. Traditionally, this deposition is thought to reinforce the cell wall and is regarded as a defense response. Surprisingly, here we found that powdery mildew resistant 4 (pmr4), a mutant lacking pathogen-induced callose, became resistant to pathogens, rather than more susceptible. This resistance was due to mutation of a callose synthase, resulting in a loss of the induced callose response. Double-mutant analysis indicated that blocking the salicylic acid (SA) defense signaling pathway was sufficient to restore susceptibility to pmr4 mutants. Thus, callose or callose synthase negatively regulates the SA pathway.     

Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy

Adrenalectomy of adult male rats resulted in a nearly complete loss of hippocampal granule cells 3 to 4 months after surgery. Nissl and immunocytochemical staining of hippocampal neurons revealed that the granule cell loss was selective; there was no apparent loss of hippocampal pyramidal cells or of gamma-amino butyric acid (GABA)-, somatostatin-, neuropeptide Y-, calcium binding protein-, or parvalbumin-containing hippocampal interneurons. The hippocampal CA1 pyramidal cells of adrenalectomized animals exhibited normal electrophysiological responses to afferent stimulation, whereas responses evoked in the dentate gyrus were severely attenuated. Corticosterone replacement prevented both the adrenalectomy-induced granule cell loss and the attenuated physiological response. Thus, the adrenal glands play a role in maintaining the structural integrity of the normal adult brain.     

The primate hippocampal formation: evidence for a time-limited role in memory storage

Clinical and experimental studies have shown that the hippocampal formation and related structures in the medial temporal lobe are important for learning and memory. Retrograde amnesia was studied prospectively in monkeys to understand the contribution of the hippocampal formation to memory function. Monkeys learned to discriminate 100 pairs of objects beginning 16, 12, 8, 4, and 2 weeks before the hippocampal formation was removed (20 different pairs at each time period). Two weeks after surgery, memory was assessed by presenting each of the 100 object pairs again for a single-choice trial. Normal monkeys exhibited forgetting; that is, they remembered recently learned objects better than objects learned many weeks earlier. Monkeys with hippocampal damage were severely impaired at remembering recently learned objects. In addition, they remembered objects learned long ago as well as normal monkeys did and significantly better than they remembered objects learned recently. These results show that the hippocampal formation is required for memory storage for only a limited period of time after learning. As time passes, its role in memory diminishes, and a more permanent memory gradually develops independently of the hippocampal formation, probably in neocortex.     

Diurnal rhythm in endoplasmic reticulum of rat liver: electron microscopic study

Electron microscopy of rat hepatocytes revealed a diurnal variation in the relative amounts of endoplasmic reticulum structures and regional differences in their distribution within the hepatic lobule. The diurnal changes in smooth and rough endoplasmic reticulum structures were compared with the diurnal changes in the hepatic microsomal enzyme hexobarbital oxidase. In the control group, at the time when enzyme activity was maximum, the amount of smooth endoplasmic reticulum was also maximum and vice versa. When the enzyme rhythm was abolished, as in blinded rats, the diurnal rhythm in the endoplasmic reticulum was also abolished.     

Feeding schedule alteration of daily rhythm in tyrosine alpha-ketoglutarate transaminase of rat liver

Liver tyrosine alpha-ketoglutarate transaminase has a daily rhythm such that in rats fed on an unrestricted basis the activity is highest at approximately 11:00 p.m. In contrast, rats fed only from 8:00 a.m. to noon show a markedly different rhythm in the enzyme, with maximum activity at 11:00 a.m. Controlling the time of food intake seems to be a useful means of studying the mechanism of the daily changes in this enzyme.     

硝普钠诱导体外培养的海马神经元凋亡的研究

目的：观察一氧化氮（NO）供体硝普钠（SNP）对体外培养的海马神经元凋亡的影响。方法：用终浓度分别为0、25、50、100、200、400、600μmol/L的SNP处理海马神经元24h，用MTT比色法分析细胞存活率，倒置显微镜、Hoechst 33258荧光染色观察凋亡的形态学改变，DNA琼脂糖凝胶分析凋亡的生化特征。结果：SNP可剂量依赖性的降低神经元的存活率，当SNP浓度为50μmol/L时，其存活率为56.2%；倒置显微镜观察可见神经元胞体固缩，突起断裂，网络消失；荧光显微镜可见染为高亮蓝色的典型凋亡小体，其细胞核明显固缩、凝聚和断裂，且随SNP剂量的增加，出现凋亡小体的细胞明显增多；50、100、200μmol/L SNP处理海马神经元，电泳图谱显示清晰的DNA梯度。结论：SNP可诱导培养的海马神经元凋亡。     

Retention deficit correlated with a deficit in the corticoid response to stress

Previous research has indicated that intracerebral injection of potassium chloride, and the resultant electrical silence of the brain, lead to the attenuation of a previously conditioned emotional response; this response may reflect conditioned fear. The data reported here indicate that the normal mobilization of corticosteroids, perhaps a second index of emotionality, is also attenuated by such injections.     

复合不育剂EP-1对小鼠空间记忆与焦虑行为的影响

EP-1是由炔雌醚和左炔诺孕酮按照1:2的比例配制而成的一种用于鼠类不育控制的激素类复合不育剂,对鼠类的繁殖及繁殖行为等有一定影响,但对鼠类空间学习与记忆、焦虑行为等非繁殖行为的影响还没有报道。为此,用0 (对照)、1.0、2.0、3.0 mg/kg剂量的EP-1对昆明小鼠(Mus musculus)进行灌胃处理,然后用Morris水迷宫和高架十字迷宫分别测定其空间记忆、焦虑行为。结果发现灌胃后15 d,剂量为2.0 mg/kg的EP-1使小鼠空间记忆能力显著下降,但30 d后其空间记忆能力有所恢复,表明2.0 mg/kg剂量的EP-1可以在一定时间范围内降低小鼠的空间记忆能力。但不同剂量的EP-1对小鼠焦虑行为无显著影响。该结果可以为从对非繁殖行为的影响的角度研究EP-1对鼠类的作用提供一定启示。     

Paradoxical fear-increasing effects of tranquilizers: evidence of repression of memory in the rat

Conditioned suppression of feeding, an index of fear, was increased rather than decreased by the administration of benzodiazepine tranquilizers or amobarbital. The drug-induced increase in conditioned fear varied directly with the intensity of the shock used in fear conditioning. The drugs had no fear-increasing effect in unshocked controls or in rats made amnesic by electroconvulsive shock given immediately after fear conditioning. These observations in animals are reminiscent of clinical reports that intraveneous amobarbital facilitates the recall of repressed traumatic experiences. The retrieval of painful memories may be inhibited or repressed in animals as well as in humans. In both cases, tranquilizers may counteract repression by disinhibition of the act of retrieval.