Centrally Induced Feline Emotional Behavior and Limbic Kindling

The threshold intensity required for electrical hypothalamic/mesencephalic stimulation to elicit emotional behavior in cats was examined chronologically during limbic kindling (n = 9/5), and without kindling (n = 3/3) for a matching control period. After the completion of primary site amygdaloid (AM) or hippocampal (HIPP) kindling, the hypothalamic defensive behavior threshold showed a +/- 20% fluctuation from the prekindling baseline with a mean tendency for reduction as in the control animals. The flight behavior threshold increased in the kindled animals, and decreased in the controls; however, the degree of change was not statistically significant. In contrast, the mesencephalic defensive behavior threshold, which was quite stable in the controls, decreased significantly upon primary (mean -13.5%) and secondary site (mean -22.2%) AM kindling, whereas the flight and screeching (sound emission) behavior threshold remained unchanged throughout kindling. The decreased or unchanged thresholds for each behavior were independent of the timing of the hypothalamic/mesencephalic stimulation after kindled generalized convulsion. The decreased mesencephalic defensive behavior threshold persisted during a 1- to 3-month rest period without kindling stimulation. These findings suggest that acquisition of feline AM-kindled seizure susceptibility is associated with a lasting facilitation of midbrain (but not hypothalamic) excitability for defensive (but not flight) behavior.     

Neuropeptide Levels after Pentylenetetrazol Kindling in the Rat

Levels of several neuropeptides were measured in the frontal cortex, dorsal hippocampus, striatum, and amygdala/pyriform cortex in rats kindled for 5 weeks by daily injection of pentylenetetrazol (30 mg/kg, i.p.). Significantly increased concentrations (by 30 - 140%) were found in all examined brain areas for neuropeptide Y, somatostatin (except hippocampus) and neurokinin-like immunoreactivity 10 days after the last kindling session. Similar but less pronounced changes were also found 24 h after the last seizure. The increase in total neurokinin-like immunoreactivity was due to a marked increase in neurokinin B as revealed by HPLC analysis. Increases in peptide levels, however, were restricted to fully kindled animals. At the same time no changes in levels of substance P, vasoactive intestinal polypeptide and calcitonin gene-regulated peptide were observed. Cholecystokinin octapeptide was enhanced only in the hippocampus (by 46%). The increases in neuropeptide Y, somatostatin, and neurokinin-like immunoreactivity subsided after 3 months. A markedly decreased seizure threshold was observed 10 days and 2 months after the final kindling session. No nerve cell degeneration was observed in kindled rats 24 h or 10 days after the last pentylenetetrazol injection. Some animals (2 of 4), however, exhibited signs of blood - brain barrier damage when examined 24 h after the last kindling session which may reflect the preceding convulsions. No such changes were detected after 10 days. The increases in peptide levels may suggest increased activity of respective neurons which, at least to some degree, may be associated with gamma-aminobutyric acid. The changes in peptide levels may be more closely related to the kindling procedure itself than to the decreased seizure threshold of the animals.     

The Effect of Generalized Absence Seizures on the Progression of Kindling in the Rat

Summary:  The involvement of the thalamus in limbic epileptogenesis has recently drawn attention to the connectivity between the nuclei of the thalamus and limbic structures. Thalamo-limbic circuits are thought to regulate limbic seizure activity whereas thalamocortical circuits are involved in the expression and generation of spike-and-wave discharges (SWDs) in the absence epilepsy models. Genetic Absence Epilepsy Rats From Strasbourg (GAERS) and WAG/Rij (Wistar Albino Glaxo from Rijswijk) are well-defined genetic animal models of absence epilepsy. We aimed to examine the duration of behavioral changes in the kindling process and the relation of SWD activity to the kindling progress in the GAERS and WAG/Rij animals. Electrodes were stereotaxically implanted into the basolateral amygdala and the cortex of rats for stimulation and recording. The animals were stimulated at the threshold for producing afterdischarges. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated using Racine's 5-stage scale. None of the GAERS animals reached stage 3, 4, or 5 after application of 30 stimulations. The WAG/Rij animals showed different rate of kindling, therefore they were further categorized into the kindling-resistant, slow-kindled, and rapid-kindled groups. The kindling-resistant animals demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation and shorter duration of afterdischarge than did the kindled WAG/Rij animals. Behavioral durations at stage 2 were longer in kindled Wistar and WAG/Rij animals compared to kindling-resistant WAG/Rij and GAERS. These results suggest that mechanisms involved in the generation of SWDs act as a counterbalance to the excitability induced by kindling.     

Memory,Narrative, and the Consequences

Drawing on papers from three different areas — evolutionary psychology, developmental psychology, sociolinguistics analysis — this commentary states that there is by now an empirically grounded and theoretically reflected memory research that has begun to break with the traditional individual‐centric orientation of the memory sciences. This break, it is argued, is the consequence of a new interest in the dialectics between memory and language, between social (or collective or collaborative) remembering and narrative. On this view, memory is taken less as a substance and more as a set of practices, of intersubjective and interpretive acts of a remembering subject.     

Differences in Kindling Development in Seven Outbred and Inbred Rat Strains

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague–Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague–Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague–Dawley and Brown–Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.     

Anterior Thalamic Inputs Are Required for Subiculum Spatial Coding,with Associated Consequences for Hippocampal Spatial Memory

Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology.SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.     

氟桂利嗪对杏仁核点燃鼠海马Bax mRNA表达的影响

目的:观察氟桂利嗪对杏仁核点燃鼠癎性发作及海马促凋亡基因Bax mRNA表达的影响。方法:建立杏仁核点燃模型,予不同剂量氟桂利嗪灌喂点燃鼠。原位杂交法检测鼠脑海马Bax mRNA表达,图像分析软件测量阳性细胞平均吸光度。结果:正常大鼠海马存在少量Bax mRNA表达阳性细胞,点燃鼠海马各区Bax mRNA表达阳性细胞数及平均吸光度增加,氟桂利嗪处理后平均吸光度下降与剂量有关。结论:氟桂利嗪具有抗癫癎效应和拮抗点燃鼠海马Bax mRNA表达的作用。     

Influence of Emotional Processing on Working Memory in Schizophrenia

Research on emotional processing in schizophrenia suggests relatively intact subjective responses to affective stimuli “in the moment.” However, neuroimaging evidence suggests diminished activation in brain regions associated with emotional processing in schizophrenia. We asked whether given a more vulnerable cognitive system in schizophrenia, individuals with this disorder would show increased or decreased modulation of working memory (WM) as a function of the emotional content of stimuli compared with healthy control subjects. In addition, we examined whether higher anhedonia levels were associated with a diminished impact of emotion on behavioral and brain activation responses. In the present study, 38 individuals with schizophrenia and 32 healthy individuals completed blocks of a 2-back WM task in a functional magnetic resonance imaging scanning session. Blocks contained faces displaying either only neutral stimuli or neutral and emotional stimuli (happy or fearful faces), randomly intermixed and occurring both as targets and non-targets. Both groups showed higher accuracy but slower reaction time for negative compared to neutral stimuli. Individuals with schizophrenia showed intact amygdala activity in response to emotionally evocative stimuli, but demonstrated altered dorsolateral prefrontal cortex (DLPFC) and hippocampal activity while performing an emotionally loaded WM-task. Higher levels of social anhedonia were associated with diminished amygdala responses to emotional stimuli and increased DLPFC activity in individuals with schizophrenia. Emotional arousal may challenge dorsal-frontal control systems, which may have both beneficial and detrimental influences. Our findings suggest that disturbances in emotional processing in schizophrenia relate to alterations in emotion-cognition interactions rather than to the perception and subjective experience of emotion per se.     

尼莫地平对杏仁核点燃鼠模型脑内谷氨酸及P-糖蛋白表达的影响

目的：观察尼莫地平对杏仁核癫痫点燃鼠模型脑内谷氨酸（Glu）及P-糖蛋白（P-gP）表达的影响。方法：选择健康雄性Wistar大鼠30只制作癫痫模型,造模成功后随机分为未点燃正常组、癫痫模型组和尼莫地平组。1周后分别取鼠脑组织,采用免疫组化检测大鼠脑内Glu和P-gp表达,比较各组表达的变化。结果：①癫痫模型组中杏仁核、海马和颞叶P-gp阳性细胞计数（分别为14．05±10．95、10．05±8．23和7．64±5．89）较未点燃正常组（4．32±6．69、3．96±3．04和2．15±1．40）和尼莫地平组（6．88±9．18、4．48±6．50和2．68±1．37）明显增多（P〈0．05）;尼莫地乎组P-gp阳性细胞数与未点燃正常组比差异无统计学意义。②癫痫模型组中杏仁核、海马和颞叶Glu的平均透光率（％）（分别为18．51±3．19、19．21±2．56和20．50±2．84）与未点燃正常组（23．03±7．29、24．88±5．55和26．11±7．17）Lh有明显降低（P〈0．05）,而尼莫地平组（19．60±4．84、20．71±6．04和21．44±5．52）与癫痫模型组比差异无统计学意义（P〉0．05）。③Glu和P．gp的表达均以杏仁核最强,其次为海马和颞叶,特别是在癫痫模型组中。结论：①尼莫地平在杏仁核电刺激点燃模型中可明显抑制杏仁核、海马、颞叶的P-gp表达,但不能抑制Glu的表达;②Glu和P-gp在杏仁核、海马和颞叶中的表达程度不同,以杏仁核表达最强。     

Kindling of the Interpeduncular Nucleus and Its Influence on Subsequent Amygdala Kindling in Rats

Summary We examined the effect of interpeduncular nucleus (IPN) kindling on subsequent amygdala (AM) kindling in rats (n = 9). Eleven to 15 daily IPN stimulations at an afterdischarge (AD)-inducing threshold (40CL1000 PA, biphasic sine waves, 1–3 s) produced progressive AD growth (9 of 9 rats) and recruitment of behavioral seizures (7 of 9 rats). The final form of the latter was generalized tonic-clonic seizures with or without a limbic seizure component. The latter was associated with ictal involvement of AM and sensorimotor cortex. Subsequent AM kindling resulted not only in more rapid kindling, but also in tonic seizure associated with a protracted loss of postural control (5–20 s) not observed in animals undergoing AM kindling without previous IPN kindling (n = 5).These findings indicate that the IPN can be kindled and that subsequent AM kindling utilizes the proconvulsant neuroplastic changes that have been already established by IPN kindling.     

Tau蛋白在点燃大鼠海马苔藓纤维出芽中的作用探讨

目的观察总tau蛋白及其p-ptauser202在戊四氮点燃癫模型海马中的表达变化,探讨其在苔藓纤维出芽中的作用。方法 180只雄性SD大鼠随机分为对照组(腹腔注射生理盐水)和模型组(腹腔注射戊四氮),均n=90。于不同的时间点应用Timm染色观察苔藓纤维出芽,免疫组化和Western blot检测各时间点海马总tau蛋白及p-ptauser202蛋白表达情况。结果模型组各时间点CA1、CA3、DG区苔藓纤维出芽较对照组明显增多,差异有统计学意义(P<0.05);模型组第1周CA1区、CA3区,第2周DG区的p-ptauser202蛋白表达与对照组比较明显增多,差异均有统计学意义(分别为CA1区P<0.05,CA3区P<0.01,DG区P<0.01);门区(H区)tau蛋白及p-ptauser202蛋白在各时间点的表达明显增多,差异有显著统计学意义(P<0.01);对照组无动态变化。结论 tau蛋白可能通过其磷酸化水平的增高参与癫点燃大鼠的苔藓纤维出芽,在癫的发生和发展中起重要作用。     

Long-Term Consequences of Severe Closed Head Injury on Episodic Memory

This is the first systematic investigation of the very long-term effects of severe closed head injury (CHI) on objective measures of memory, and the first to employ both a normal control group and an other injury control group consisting of spinal cord injury (SCI) patients. The CHI group displayed significantly poorer performance on every memory measure, and the effect sizes were large. This impairment in episodic memory is neither due to pre-injury nor post-injury differences between CHI and normal control subjects because the same differences were found when the CHI group was compared to a group of SCI patients. The findings demonstrate severe impairment in learning and retention many years after sustaining a severe CHI, which is likely in part due to the bilateral hippocampal damage shown in neuropathological studies. This life-long memory impairment needs to be addressed by community service programs.     

Emotional Human-Machine Conversation Generation Based on Long Short-Term Memory

With the rise in popularity of artificial intelligence, the technology of verbal communication between man and machine has received an increasing amount of attention, but generating a good conversation remains a difficult task. The key factor in human-machine conversation is whether the machine can give good responses that are appropriate not only at the content level (relevant and grammatical) but also at the emotion level (consistent emotional expression). In our paper, we propose a new model based on long short-term memory, which is used to achieve an encoder-decoder framework, and we address the emotional factor of conversation generation by changing the model’s input using a series of input transformations: a sequence without an emotional category, a sequence with an emotional category for the input sentence, and a sequence with an emotional category for the output responses. We perform a comparison between our work and related work and find that we can obtain slightly better results with respect to emotion consistency. Although in terms of content coherence our result is lower than those of related work, in the present stage of research, our method can generally generate emotional responses in order to control and improve the user’s emotion. Our experiment shows that through the introduction of emotional intelligence, our model can generate responses appropriate not only in content but also in emotion.     

Number of Synaptic Vesicles in Rat Cortex Immediately After Cessation of the Self-Sustained Afterdischarge During Kindling

The sensorimotor area of rat cerebral cortex was subjected to repetitive electrical stimulation at 10-min intervals; this led to progressive lengthening of self-sustained afterdischarges (SSADs). At 50-60 s after cessation of the third SSAD the brains of the animals were perfused transaortally with fixing fluid, and a quantitative electron microscopic analysis of type I synapses in the second cortical layer of the sensorimotor area of the contralateral hemisphere was carried out. In a zone 0.1 micron wide adjacent to the presynaptic membrane in the active zone, the number of synaptic vesicles (converted to the number per 0.01 micron2 area) in the experimental animals fell by 64.6%. In a zone of the same width 0.1 micron distant from the presynaptic membrane, it fell by 67.6%. The mean absolute synaptic vesicle count per presynaptic bag section fell by 66.6%. The number of synapses showing signs of exocytosis rose in the experimental animals from 3.8 to 5.9%, while the number with clearly demonstrable exocytosis rose from 0.7 to 11.4%. The proportion of synapses with signs of (clearly demonstrable) endocytosis rose from 2.8% (2.1%) in the controls to 7.1% (3.7%) in the experimental rats. In the experimental and control animals we demonstrated complex vesicle formation in 4.3 and 3.8%, respectively, of the synapses and dense-cored vesicles in 7.7 and 2.8%, respectively, of the synapses. We consider changes in the number and formation of synaptic vesicles to be signs of exhaustion of the synapses caused by the previous epileptic seizure, which simultaneously activates mechanisms of vesicle formation.     

Rat Hippocampal Kindling Induces Changes in the Glutamate Receptor mRNA Expression Patterns in Dentate Granule Neurons

The expression level of the mRNAs encoding the Flip and Flop versions of the AMPA-selective glutamate receptor subunits A, B, C and D was studied using in situ hybridization in the hippocampus of rats kindled by Schaffer collateral/commissural fibre stimulation. The expression levels of the Flip variant of GluR-A, B and C mRNAs were bilaterally enhanced in the dentate granule neurons of fully kindled animals 24 h after the last seizure. These changes were already observed after the sixth kindling stimulation (preconvulsive-stage), but not after a single afterdischarge. Four weeks after the last seizure, when the animals were still hypersensitive to kindling stimulations, only GluR-A Flip expression was enhanced. These results suggest that kindling epileptogenesis is accompanied by an increased number and enhanced sensitivity of the expressed AMPA type glutamate receptors in the fascia dentata, leading to an enhanced excitatory synaptic transmission which may contribute to the process of kindling epileptogenesis.