Feel the heat: The effect of temperature on development, behavior and central pattern generation in 3rd instar Calliphora vicina larvae

Like in all poikilothermic animals, higher temperatures increase developmental rate and activity in Calliphora vicina larvae. We therefore could expect temperature to have a persistent effect on the output of the feeding and crawling central pattern generators (CPGs). When confronted with a steep temperature gradient, larvae show evasive behavior after touching the substrate with the cephalic sense organs. Beside this reflex behavior the terminal- and dorsal organ might also mediate long term CPG modulation. Both organs were thermally stimulated while their response was recorded from the maxillary- or antennal nerve. The terminal organ showed a tonic response characteristic while the dorsal organ was not sensitive to temperature. Thermal stimulation of the terminal organ did not affect the ongoing patterns of fictive feeding or crawling, recorded from the antennal- or abdominal nerve respectively. A selective increase of the central nervous system (CNS) temperature accelerated the motor patterns of both feeding and crawling. We propose that temperature affects centrally generated behavior via two pathways: short term changes like thermotaxis are mediated by the terminal organ, while long term adaptations like increased feeding rate are caused by temperature sensitive neurons in the CNS which were recently shown to exist in Drosophila larvae.     

Does serotonin influence aggression? comparing regional activity before and during social interaction

Serotonin is widely believed to exert inhibitory control over aggressive behavior and intent. In addition, a number of studies of fish, reptiles, and mammals, including the lizard Anolis carolinensis, have demonstrated that serotonergic activity is stimulated by aggressive social interaction in both dominant and subordinate males. As serotonergic activity does not appear to inhibit agonistic behavior during combative social interaction, we investigated the possibility that the negative correlation between serotonergic activity and aggression exists before aggressive behavior begins. To do this, putatively dominant and more aggressive males were determined by their speed overcoming stress (latency to feeding after capture) and their celerity to court females. Serotonergic activities before aggression are differentiated by social rank in a region-specific manner. Among aggressive males baseline serotonergic activity is lower in the septum, nucleus accumbens, striatum, medial amygdala, anterior hypothalamus, raphe, and locus ceruleus but not in the hippocampus, lateral amygdala, preoptic area, substantia nigra, or ventral tegmental area. However, in regions such as the nucleus accumbens, where low serotonergic activity may help promote aggression, agonistic behavior also stimulates the greatest rise in serotonergic activity among the most aggressive males, most likely as a result of the stress associated with social interaction.     

Selective serotonin reuptake inhibitor (fluoxetine) decreases the effects of ghrelin on memory retention and food intake

Ghrelin (Ghr) is an appetite stimulating hormone that is produced peripherally, by the stomach, and centrally as well. Previous investigations show that Ghr increases food intake and memory retention in rats, and that extra-hypothalamic structures, such as the hippocampus, participate in these effects. In the present work we analyzed the effect on food intake and memory retention induced by Ghr after serotonin (5-HT) availability modification at the serotoninergic synapses. Animals only treated with a selective serotonin reuptake inhibitor (SSRI), fluoxetine (FLU) 5 mg/kg or clomipramine (CLO) 2.5 and 5 mg/kg, showed a significant reduction in both food intake and memory retention. On the contrary, Ghr administration induces a significant increase in food intake and a dose-dependent increase in short and long term memory retention. When the animals were treated with FLU prior to Ghr injection, the food intake induced, as well as the expression of short and long term memory retention, was decreased. In conclusion, evidence presented in this paper suggests that the effects of Ghr on both feeding and memory retention in extra-hypothalamic structures such as the hippocampus, could depend on the availability of 5-HT.     

Blockage of induced pseudopregnancy by electrochemical stimulation of the limbic system.

Pseudopregnancy induced by cervical stimulation was inhibited by acute electrochemical stimulation of the corticomedial amygdala or dorsal hippocampus under sodium pentobarbital anesthesia (40 mg/kg) in adult, cyclic female Sprague-Dawley rats. The degree to which pseudopregnancy was blocked depended on temporal conditions of brain stimulation and sodium pentobarbital administration. Pentobarbital alone had a suppressing effect on the incidence of pseudopregnancy, especially when it preceded cervical stimulation. Limbic stimulation before cervical stimulation had a tendency to potentiate the suppression of pseudopregnancy by pentobarbital. After cervical stimulation, hippocampal stimulation tended to inhibit the development of pseudopregnancy, potentiating the pentobarbital suppression, while amygdala stimulation tended to override the pentobarbital blockage of pseudopregnancy. These findings suggest a negative influence of these two limbic structures and pentobarbital on the secretion of prolactin.     

Induction and blockade of epileptic foci by intracerebral injection of glutamatergic agonists and antagonists in frerly moving cats

The aim of the present work was to test in adult cats the capability of three glutamatergic agonists, NMDA, AMPA and ACDP as epileptogenic agents. Drugs were microinjected in amygdala or hippocampus, and once generated an epileptic focus three selective glutamatergic antagonists NMDA, CNQX and MCPG, were tested. Before and after injection both the EEG and the behavior were continuously monitored. The results were as follows: 1) AMPA showed a greater capability than NMDA or ACPD to generate a chronic epileptic focus; 2) AMPA elicited a greater epileptogenic effect in hippocampus than in amygdala; NMDA had similar epileptogenic effect in both cited structures, and ACPD had not effect; 3) of the three glutamatergic antagonists used to block a long lasting focus, the most effective one was CNQX, which showed a greater effect in hippocampus than in amygdala; 4) comparison between the epileptogenic effect of AMPA and kainic acid (first paper) in the same structure, showed that kainic acid is about 15 fold more epileptogenic. A discussion of the probable mechanisms of these results was undertaken.     

Analysis of the effects of electrical stimulation of certain limbic structures

It has been established that stimulation of the structures of the limbic system (hippocampus, amygdaloid complex, septum) and the medial nucleic of the thalamus of rabbits in conditions of free behavior elicits four basic types of behavioral reactions: arousal, orientation-investigatory, aggressive-defensive and various epileptiform (convulsive) reactions. Activation of behavior, i.e., arousal and the orientation-investigatory reaction, constantly appear on stimulation of the unspecific thalamic nuclei. The aggressive-defense reaction is elicited by stimulating the nuclei of the amygdaloid complex of the ventral part of the hippocampus and the ventromedial nuclei of the thalamus. The epileptiform reactions are most readily reproduced on stimulation of the amygdaloid complex and the ventral part of the hippocampus. The threshold for the appearance of discharges of the aftereffect is very low. The latter are more sustained on stimulation of the basolateral part of the amygdala and the ventral part of the hippocampus. In rabbits as compared with higher animals the discharges on stimulation rapidly spread not only to the limbic system but also to the reticular formation and the neocortex.Kharkov Medical Institute. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 194–201, September–October, 1969.     

Melanin-concentrating hormone (MCH) modifies memory retention in rats

The purpose of the present study was to evaluate the possible effect of melanin-concentrating hormone (MCH) on learning and memory by using the one-trial step-down inhibitory avoidance test in rats. The peptide was infused into hippocampus, amygdala, and entorhinal cortex. MCH caused retrograde facilitation when given at 0 or 4 h post-training into hippocampus, but only at 0 h into amygdala. From these results, it seems that MCH modulates memory early after training by acting on both the amygdala and hippocampus and, 4 h after training, on the hippocampus.     

Ventral Tegmental Area Inactivation Suppresses the Expression of CA1 Long Term Potentiation in Anesthetized Rat

The hippocampus receives dopaminergic projections from the ventral tegmental area (VTA). Modulatory effect of dopamine on hippocampal long term potentiation (LTP) has been studied before, but there are conflicting results and some limitations in previous reports. Most of these studies show a significant effect of dopamine on the late phase of LTP in CA1 area of the hippocampus, while few reports show an effect on the early phase. Moreover, they generally manipulated dopamine receptors in the hippocampus and there are few studies investigating influence of the VTA neural activity on hippocampal LTP in the intact brain. Besides, VTA neurons contain other neurotransmitters such as glutamate and GABA that may modify the net effect of dopamine. In this study we examined the effect of VTA reversible inactivation on the induction and maintenance of early LTP in the CA1 area of anesthetized rats, and also on different phases of learning of a passive avoidance (PA) task. We found that inactivation of the VTA by lidocaine had no effect on CA1 LTP induction and paired-pulse facilitation, but its inactivation immediately after tetanic stimulation transiently suppressed the expression of LTP. Blockade of the VTA 20 min after tetanic stimulation had no effect on the magnitude of LTP. Moreover, VTA inactivation immediately after training impaired memory in the passive avoidance task, while its blockade before or 20 min after training produced no memory deficit. It can be concluded that VTA activity has no effect on CA1 LTP induction and acquisition of PA task, but involves in the expression of LTP and PA memory consolidation.     

Electrical responses of olfactory structures and amygdala of dogs in the paradoxical phase of sleep

Electrical activity of the olfactory bulb, olfactory tubercle, amygdala, hippocampus, hypothalamus, and neocortex in the various phases of natural sleep was studied in chronic experiments on dogs under conditions close to those of free behavior. During paradoxical sleep it was found that a high-frequency synchronized rhythm of sinusoidal waves with a frequency of 36–42 Hz arises in the olfactory structures and amygdala. Generation of this activity during paradoxical sleep, by contrast with wakefulness, was unconnected with stimulation of the olfactory receptors and was probably purely central in origin. A study of the dynamics of the olfacto-amygdaloid rhythm during the paradoxical phase, and its comparison with somatic, autonomic, and EEG correlates of sleep, led to the conclusion that this rhythm is a specific EEG correlate of the paradoxical phase of sleep in dogs.     

转录因子Egr-1参与长期性恐惧记忆和焦虑

锌指转录因子点Egr-1在将细胞外信号和胞内基因表达的变化相耦联过程中发挥重要的作用。海马和杏仁体是记忆形成和储存的两个主要的脑区。在海马和杏仁体中,Egr-1可被长时程增强（long-term potentiation,LTP）和学习过程上调。在Egr-1敲除小鼠上观察到晚时相声音恐惧记忆受损,而短时的痕迹和场景记忆却不受影响;另外,在Egr-1敲除小鼠上,用theta burst刺激杏仁体和听觉皮层所引起的突触增强被明显减弱或完全阻断。因此,我们的研究表明,转录因子Egr-1选择性地在晚时相听觉恐惧记忆中发挥作用。     

Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I

MCF-7 cells were grown in serum free medium (Dulbecco MEM without phenol red, supplemented with Costar SF-1 without insulin). Insulin was added as required and gave dose dependent growth stimulation at concentrations between 5 and 10,000 nM. Identical growth response curves were obtained for thymidine uptake and cell number. Oestradiol and insulin-like growth factor I (IGF-I) added individually both gave a dose dependent stimulation of cell growth in serum free medium containing 50 nM insulin. The growth stimulatory effect of oestradiol was to a large extent inhibited with suramine, a general inhibitor of growth factors, indicating that the effect of oestradiol was mediated through stimulating autocrine secretion of a growth factor.

To investigate a possible link between the effects of oestradiol and IGF-I, a specific IGF-I receptor antibody (IR-3), 10 μg/ml was used. These experiments were carried out with 2.5 nM insulin in the medium, a concentration at which insulin had no growth stimulatory effect. Stimulation was carried out for 18 h before assay of thymidine uptake. The effect of oestradiol was not significantly reduced by IR-3, indicating that IGF-I was not an autocrine mediator of oestradiol stimulation of cell growth under these conditions, whereas IR-3 extensively reduced growth stimulation by IGF-I. On long term stimulation (5 days) oestradiol had a marked stimulatory effect on cell number and IR-3 almost totally abrogated this effect. When oestradiol (1 nM) and IFG-I (2.5 nM) were added together, the combined effect on thymidine incorporation and cell number was significantly greater than additive. This synergistic effect on the IGF-I growth response was totally abolished by the IGF-I receptor antibody. The results suggest a cooperative interaction of oestradiol and IGF-I. It is concluded that growth stimulation of MCF-7 cells by long term treatment with oestradiol may be mediated through autocrine secretion of IGF-I.

The effect of short term stimulation of thymidine incorporation suggest that the growth response of oestradiol is more complex, and indicate that a cooperative interaction with IGF-I is involved, which is unrelated to stimulated autocrine secretion.     

Aluminum-Induced Cholinergic Deficits in Different Brain Parts and Its Implications on Sociability and Cognitive Functions in Mouse

Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer’s disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl₃ (250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication.     

Neonatal Morphine Administration Leads to Changes in Hippocampal BDNF Levels and Antioxidant Enzyme Activity in the Adult Life of Rats

It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 μg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.     

Effects of food texture change on metabolic parameters: short- and long-term feeding patterns and body weight

A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.     

Aphid-induced reduction of shoot and root growth in Douglas-fir seedlings

1. The short‐ and long‐term effects of photosynthate removal by sap‐sucking herbivores on plant growth were examined by experimentally manipulating densities of an aphid Cinara pseudotsugae (Wilson) on 2‐year‐old Douglas‐fir seedlings Pseudotsuga menziesii (Mirb.) Franco under greenhouse conditions. An 18‐week test was conducted to determine short‐term effects. Effects of long‐term aphid feeding were examined by exposing seedlings to aphid feeding for two consecutive growing seasons. A third experiment evaluated the extent of recovery during 1 year following a single season of aphid feeding. At least 35 seedlings were used in each test. 2. Volume and dry weight of both shoots and roots decreased significantly with increasing aphid feeding in all three experiments. 3. The most significant and severe aphid effect was reduced root tissue density, suggesting carbohydrate depletion due to translocation from roots to shoots. 4. There was no sign of recovery, of either root or shoot growth, during the year following one season of feeding. 5. The results of this study indicate that short‐term feeding by aphids can affect plant growth and structure for a relatively long time.     

Effects of hyperdynamic fields on input-output relationships and long-term potentiation in the rat hippocampus

The effects of a 2G force environment on synaptic plasticity were examined in the rat hippocampus. Field potentials from neurons in the CA1 pyramidal cell layer were evoked by stimulation of the afferent Schaffer collateral/commissural fibers in an in vitro slice preparation. Input-output (I-O) relationships of the circuit were determined before and after tetanizing stimuli given to induce long term potentiation (LTP), a form of neural plasticity. I-O curves from animals exposed to 2G via centrifugation for either 2 or 14 days were not different from those obtained in control (1G) animals. Similarly, induction of LTP was equivalent in all groups, showing increases in maximum amplitude, slope and midpoint response of the fitted Boltzmann functions compared to un-tetanized controls. Comparison of slices from dorsal and ventral hippocampus showed the location of the slice had no effect of LTP expression. We conclude that, in contrast to other reports of functional changes in the central nervous system under altered force environments, cellular mechanisms of synaptic plasticity, which may underlie learning and memory, are preserved in the hippocampus.     

Methylphenidate improves the behavioral and cognitive deficits of neurogranin knockout mice

Neurogranin (Ng), a brain‐specific calmodulin‐binding protein, is expressed highly in hippocampus, and is important for cognitive function. Deletion of the Ng gene from mice caused attenuation of signal reaction cascade in hippocampus, impairments in learning and memory and high frequency stimulation‐induced long‐term potentiation (LTP). Environmental enrichment alone failed to improve cognitive function. In this study, behavioral testing revealed that Ng knockout (NgKO) mice were both hyperactive and socially withdrawn. Methylphenidate (MPH) was given to mice while they were also kept under an enrichment condition. MPH treatment reduced the hyperactivity of NgKO mice tested in both the open field and forced swim chamber. MPH improved their social abilities such that mice recognized and interacted better with novel subjects. The cognitive memories of MPH‐treated mutants were improved in both water maze and contextual fear conditioning tests. High frequency stimulation‐induced LTP of NgKO mice was also improved by MPH. The present treatment regimen, however, did not fully reverse the deficits of the mutant mice. In contrast, MPH exerted only a minimal effect on the wild type mice. At the cellular level, MPH increased the number of glial fibrillary acidic protein‐positive cells in hippocampus, particularly within the dentate gyrus of NgKO mice. Therefore it will be of interest to determine the nature of MPH‐mediated astrocyte activation and how it may modulate behavior in future studies. Taken together these NgKO mice may be useful for the development of better drug treatment to improve cognitive and behavioral impairments.     

Prior pregastric food stimulation and gastrin-releasing peptide1-27 (GRP) synergize to inhibit sham feeding.

The hypothesis that prior pregastric food stimulation is sufficient to reveal an inhibitory effect of gastrin-releasing peptide1-27 (GRP) on sham feeding was tested in 11 male rats equipped with chronic gastric cannulas. Rats were sham fed a high-carbohydrate solution during a 45-min test session, after 17-h food deprivation. GRP (16 or 32 microg/kg) or saline was injected intraperitoneally either at the onset or 5 or 15 min after the onset of sham feeding. This allowed for a 0-, 5-, or 15-min period of pregastric food stimulation before GRP or saline injections. Sham intake was recorded every 5 min, and behavior was observed every minute. GRP inhibited sham feeding when it was administered after 5 or 15 min of prior pregastric food stimulation, but not when it was administered at test onset. A nonsignificant increase in resting behavior and decrease in feeding behavior were associated with the decrease in sham feeding. No anomalous behaviors were noted. We conclude that a synergy between GRP and prior pregastric, presumably oral, food stimulation is sufficient to inhibit sham feeding.     

Ontogenetic Behavior and Dispersal of Sacramento River White Sturgeon, <Emphasis Type="BoldItalic">Acipenser Transmontanus</Emphasis>, with a Note on Body Color

Synopsis We studied Sacramento River white sturgeon, Acipenser transmontanus, in the laboratory to develop a conceptual model of ontogenetic behavior and provide insight into probable behavior of wild sturgeon. After hatching, free embryos initiated a low intensity, brief downstream dispersal during which fish swam near the bottom and were photonegative. The weak, short dispersal style and behavior of white sturgeon free embryos contrasts greatly with the intense, long dispersal style and behavior (photopositive and swimming far above the bottom) of dispersing free embryos of other sturgeon species. If spawned eggs are concentrated within a few kilometers downstream of a spawning site, the adaptive significance of the free embryo dispersal is likely to move fish away from the egg deposition site to avoid predation and reduce fish density prior to feeding. Larvae foraged on the open bottom, swam <1 m above the bottom, aggregated, but did not disperse. Early juveniles initiated a strong dispersal with fish strongly vigorously swimming downstream. Duration of the juvenile dispersal is unknown, but the strong swimming likely disperses fish many kilometers. Recruitment failure in white sturgeon populations may be a mis-match between the innate fish dispersal and post-dispersal rearing habitat, which is now highly altered by damming and reservoirs. Sacramento River white sturgeon has a two-step downstream dispersal by the free embryo and juvenile life intervals. Diel activity of all life intervals peaked at night, whether fish were dispersing or foraging. Nocturnal behavior is likely a response to predation, which occurs during both activities. An intense black-tail body color was present on foraging larvae, but was weak or absent on the two life intervals that disperse. Black-tail color may be an adaptation for avoiding predation, signaling among aggregated larvae, or both, but not for dispersal.     

Neuroanatomical Profile of Antimaniac Effects of Histone Deacetylases Inhibitors

An increasing number of studies have evaluated the potential therapeutic relevance of histone deacetylases (HDAC) inhibitors in mood disorder including bipolar disorder (BD). It has been suggested that the anterior limbic, which controls impulsivity and psychosis, is dysfunctional in BD. The present studies aims to evaluate the effects of microinjection of HDAC inhibitors in the ventricle, amygdala, striatum, prefrontal, and hippocampus on m-amphetamine-induced manic-like behavior in rats. Rats were given a single intracerebral (in the ventricle, amygdala, striatum, prefrontal, or hippocampus) injection of artificial cerebrospinal fluid, sodium butyrate (SB), or valproate (VPA) followed by an intraperitoneal injection of saline or m-AMPH 2 h before the open-field task. The activity of HDAC was evaluated in amygdala, striatum, prefrontal, and hippocampus of animals. The microinjection of SB and VPA in the ventricle, amygdala, striatum, and prefrontal, but not in hippocampus blocked the hyperactivity induced by m-AMPH. In addition, SB and VPA inhibited the HDAC activity; however, this effect varied depending on the experimental procedure and the brain structure evaluated. Our results suggest that the antimanic effects of SB and VPA, HDAC inhibitors, are related to the amygdala, striatum, and prefrontal, but not the hippocampus. More studies are needed to clarify the therapeutic effects of the HDAC inhibitor in BD and thereby develop new drugs.