Vasopressin analogues and spatial working memory in the 24-arm radial maze

The effect of vasopressin analogues dAVP, dDAVP, and desgly NH₂ dDAVP on working memory was tested in the 24-arm radial maze in twelve 6-month-old and twelve 19-month-old rats. No age dependent effects were found. All three peptides tested (3 μg/kg) tended to improve the performance but only the desgly NH₂ dDAVP significantly decreased the number of errors. A second application of desgly NH₂ dDAVP was ineffective. The specificity of activation of memory mechanisms by desgly NH₂ dDAVP can be questioned.     

Alpha1-adrenergic receptor antagonist tamsulosin ameliorates aging-induced memory impairment by enhancing neurogenesis and suppressing apoptosis in the hippocampus of old-aged rats

Age-related memory decline is closely associated with decreased neurogenesis and increased apoptosis in the hippocampus. Noradrenaline exerts its effect by selectively binding to and activating adrenergic receptors (ARs). Tamsulosin, α₁-AR antagonist, is reported to have access to the brain and interact with α₁-AR. In this study, the effects of tamsulosin on short-term and spatial learning memory in terms of neurogenesis and apoptosis were investigated using rats. Step-down avoidance test for short-term memory and radial 8-arm maze test for spatial learning memory were conducted. Neurogenesis was detected by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry and apoptosis was evaluated by caspase-3 immunohistochemisty and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNE) staining. Western blot for protein kinase C (PKC), cAMP-responsive element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), phosphatidylinositol 3-kinase (PI 3-kinase), Akt, Bcl-2, and Bax was conducted. In the aged rats, short-term and spatial learning memory was declined. Hippocampal nerogenesis was suppressed and hippocampal apoptosis was enhanced in the aged rats. In addition, phosphorylation of PKCα, CREB, PI-3 kinase, and Akt was decreased in the hippocampus of old-aged rats. Tamsulosin activated PKC/CREB and PI-3 kinase/Akt pathways. With these pathways, BDNF-TrkB signaling enhanced hippocampal neurogenesis and suppressed apoptosis in the old-aged rats. As the results, tamsulosin improved performance of short-term and spatial learning memory in the aged rats.     

Differential Role of Hippocampal cAMP-Dependent Protein Kinase in Short- and Long-Term Memory

One-trial step-down inhibitory (passive) avoidance training is followed by two peaks of cAMP-dependent protein kinase (PKA) activity in rat CA1: one immediately after training and the other 3 h later. The second peak relies on the first: Immediate posttraining infusion into CA1 of the inhibitor of the regulatory subunit of PKA, Rp-cAMPS, at a dose that reduces PKA activity during less than 90 min, cancelled both peaks. Long-term memory (LTM) of this task measured at 24 h depends on the two peaks: Rp-cAMPS given into CA1 0 or 175 min posttraining, but not between those times, blocked LTM. However, the effect of immediate posttraining Rp-cAMPS on LTM could not be reversed by the activator of the regulatory subunit of PKA, Sp-cAMPS, given at 180 min, which suggests that, for LTM, the first peak may be more important than the second. When given at 0, 22, 45, or 90, but not at 175 min from training, Rp-cAMPS blocked short-term memory (STM) measured at 90 or 180 min. This effect of immediate posttraining Rp-cAMPS infusion on STM but not that on LTM was readily reversed by Sp-cAMPS infused 22 min later. On its own, Sp-cAMPS had effects exactly opposite to those of the inhibitor. It enhanced LTM when given at 0 or 175 min from training, and it enhanced STM when given at 0, 22, 45, or 90 min from training. These findings show that STM and LTM formation require separate PKA-dependent processes in CA1. STM relies on the continued activity of the enzyme during the first 90 min. LTM relies on the two peaks of PKA activity that occur immediately and 180 min posttraining.     

Inhibition of poly (ADP-ribose) polymerase and caspase-3, but not caspase-1, prevents apoptosis and improves spatial memory of rats with twice-repeated cerebral ischemia

The effect of inhibition of PARP [(poly (ADP-ribose) polymerase], caspase-3 and caspase-1 on twice-repeated ischemia-induced apoptosis and memory impairment were examined. The twice repeated ischemia was induced by four-vessel occlusion method in which a 10 min ischemic episode was repeated once after 60 min. The spatial memory was assessed using 8-arm radial maze. The results of this study showed that the repeated ischemia impaired memory and induced apoptosis in hippocampus CA1 field after 7 days. Moreover, 3-aminobezamide (10 mg/kg i.v.), a PARP inhibitor, and Ac-DEVD-CHO (8.4 microg/5 microL i.c.v., bilaterally), a caspase-3 inhibitor, decreased apoptosis by 45% and 58% respectively. Both drugs reduced the error choices, but 3-aminobezamide additionally increased the correct choices and improved the memory when either drug was injected immediately after the ischemic insult. The results also showed that inhibition of interleukin-1beta-converting enzyme, ICE (caspase-1) by Z-ASP-DCB-CH2 (100 microg/kg i.c.v., bilaterally) neither decreased apoptosis (13% reduction) nor improved memory of the ischemic rats. These results suggest that direct inhibition of PARP and caspase-3, but not of caspase-1, prevents apoptosis and improves spatial memory impaired by repeated ischemia.     

Capacity of working memory in rats as determined by performance on a radial maze

Capacity of the working memory was tested in 12 rats highly overtrained in the 12- and 24-arm radial mazes. Asymptotic performance levels were characterized by 1.01 and 2.78 errors/trial in the 12- and 24-arm mazes, respectively. The incidence of errors increased from 31% on the last choice in the 12-arm maze to 51% on choices 23 and 24 in the 24-arm maze, but remained significantly below the expected error probability of about 85%. Linear extrapolation of the above trend to mazes with more arms suggests working memory capacity of 40 to 50 items. When two trials in a 12-arm maze were repeated in immediate succession, error incidence increased from 1.17 in the first trial to 2.13 in the second trial. The tendency to avoid choice repetition could be observed in any string of 12 continuous choices, but was weakest in segments divided by trial boundary (2.48 errors in choices 7 to 18). With a different trial separation (choices 1–6 and 19–24 in maze A, choices 7–18 in an adjacent maze B) errors dropped to 1.09 in B but increased to 2.30 in A. It is concluded that radial maze performance reflects avoidance of choice repetition which is improved by recognition of trial boundaries and is adversely influenced by forgetting and interference.     

The Rate- and Species-Dependence of Short-Term Memory in Cardiac Myocytes

Short-term memory is an intrinsic property of paced cardiac myocytes that reflects the influence of pacing history, and not just the immediately preceding diastolic interval (DI), on the action potential duration (APD). Although it is recognized that short-term memory affects the dynamics of cardiac myocytes in general, and the onset of irregular cardiac rhythm in particular, its has never been adequately quantified or measured directly in experiments or numerical simulations, mainly due to the absence of appropriate techniques. As a result, very little is known about the rate- and species dependent behavior of short-term memory. In this study, we introduce a new approach that allows one to estimate how much short-term memory, M _S, is present in the cardiac myocyte at different pacing rates. The new quantification is based on the fact that pacing history affects not only the APD, but the entire dynamics of paced cardiac myocytes, in particular the restitution curve. Using the patch clamp technique and numerical simulations, we measured short-term memory restitution—the dependence of M _S on the cycle length—in isolated rabbit and guinea pig ventricular myocytes. In both species, M _S is rate- and species-dependent, displaying a biphasic behavior as a function of cycle length. Moreover, our results indicate that there is a significant difference in M _S measured between both species at small cycle lengths. Numerical simulations suggest that the kinetics of the rapidly activating delayed rectifier potassium current I _Kr is partially responsible for this difference.     

On the time course of short-term forgetting: a human experimental model for the sense of balance

The primary aim of this study was to establish whether the decline of the memory of an angular displacement, detected by the semicircular canals, is best characterized by an exponential function or by a power function. In 27 subjects a conflict was created between the semicircular canals and the graviceptive systems. Subjects were seated, facing forwards, in the gondola of a large centrifuge. The centrifuge was accelerated from stationary to 2.5G_z. While the swing out of the gondola (66°) during acceleration constitutes a frontal plane angular-displacement stimulus to the semicircular canals, the graviceptive systems persistently signal that the subject is upright. During 6 min at 2.5G_z the perceived head and body position was recorded; in darkness the subject repeatedly adjusted the orientation of a luminous line so that it appeared to be horizontal. Acceleration of the centrifuge induced a sensation of tilt which declined with time in a characteristic way. A three-parameter exponential function (Y = Ae^−bt + C) and a power function (Y = At^−b + C) were fitted to the data points. The inter-individual variability was considerable. In the vast majority of cases, however, the exponential function provided a better fit (in terms of RMS error) than the power function. The mean exponential function was: y = 27.8e^−0.018t + 0.5°, where t is time in seconds. Findings are discussed with connection to possible underlying neural mechanisms; in particular, the head-direction system and short-term potentiation and persistent action potential firing in the hippocampus are considered.     

有氧运动改善AD模型APP/PS1双转基因小鼠中枢神经元线粒体融合分裂动态平衡

线粒体融合分裂平衡是线粒体动力学的需要。本研究观察12周规律有氧运动对APP/PS1双转基因小鼠中枢神经元线粒体融合分裂动态平衡的影响。本研究采用3月龄雄性APP/PS1小鼠（AD模型）随机分为AD安静组（AS）、AD运动组（AE）,同月龄雄性C57BL/6J小鼠做正常对照组（CS）。AE组进行12周规律跑台运动,5 d/周,60 min/d。前10 min运动速度12 m/min,后50 min运动速度15 m/min,跑台坡度为0°。八臂迷宫实验检测小鼠工作记忆错误频率和参考记忆错误频率;Western印迹检测小鼠皮层、海马组织中线粒体分裂蛋白Drp1和Fis1的含量,以及Drp1的活性（p-Drp1-Ser616）、线粒体融合蛋白Mfn1、Mfn2、Opa1的表达水平;透射电镜观察皮层、海马线粒体形态结构、健康线粒体比率及线粒体平均直径。本研究证实AS组较CS组工作记忆错误频率显著提高（P<0.05）,12周有氧运动显著降低工作记忆错误频率（P<0.05）。AS组小鼠皮层Fis1蛋白和海马脑区Drp1、Fis1蛋白表达水平及皮层、海马脑区Drp1蛋白的活性增加（P<0.05）。而皮层Mfn1和海马Mfn1、Mfn2蛋白表达水平显著降低（P<0.05）。12周有氧运动显著减低Fis1、Drp1蛋白表达及Drp1蛋白的活性,提高Mfn1、Mfn2蛋白表达水平（P<0.05）。AS组小鼠皮层、海马线粒体多呈现球形,部分线粒体膜结构消失,线粒体嵴结构紊乱。且AS组较CS组小鼠健康线粒体比率降低、直径缩短。12周规律有氧运动可明显改善线粒体形态和结构,提高健康线粒体比率及直径。本研究提示,12周规律有氧运动可有效抑制皮层、海马脑区线粒体分裂蛋白Drp1和 Fis1的表达,降低Drp1的活性（p-Drp1-Ser616）,上调线粒体融合蛋白Mfn1、Mfn2的蛋白表达水平,改善线粒体形态和结构以促进线粒体质量控制,是有氧运动改善AD模型空间学习记忆能力的分子机制之一。     

Hemispheric differences in evoked potentials to pictures of faces in the left and right visual fields

Fifteen right-handed women evaluated the similarity of two faces presented to them either in the left or in the right visual field. The subjects' task was to decide whether the faces were the same or different and accordingly to press a button or abstain from doing so. Errors made by the subjects and the visual evoked potentials (VEPs) from points O₁ and O₂ referred to point C_z were recorded. Behavioural and electrophysiological results demonstrated the superiority of the right hemisphere in the perception of faces. The subjects made fewer errors when faces were presented in the left visual field. The number of errors also decreased when the presented faces were different from each other. Analysis of the VEPs indicates the existence of hemispheric asymmetry as early as 100 msec after the first stimulus disappeared. The asymmetry is larger in response to the second stimulus. On the basis of these results we conclude that differentiation in hemispheric functions takes place in the phase of short-term memory. The smaller number of errors made when the presented faces were different we explain by the strategy applied by the subjects.     

Molecular pharmacological dissection of short- and long-term memory

1. It has been discussed for over 100 years whether short-term memory (STM) is separate from, or just an early phase of, long-term memory (LTM). The only way to solve this dilemma is to find out at least one treatment that blocks STM while keeping LTM intact for the same task in the same animal.2. The effect of a large number of treatments infused into the hippocampus, amygdala, and entorhinal, posterior parietal or prefrontal cortex on STM and LTM of a one-trial step-down inhibitory avoidance task was studied. The animals were tested at 1.5 h for STM, and again at 24 h for LTM. The treatments were given after training.3. Eleven different treatments blocked STM without affecting LTM. Eighteen treatments affected the two memory types differentially, either blocking or enhancing LTM alone. Thus, STM is separate from, and parallel to the first hours of processing of, LTM of that task.4. The mechanisms of STM are different from those of LTM. The former do not include gene expression or protein synthesis; the latter include a double peak of cAMP-dependent protein kinase activity, accompanied by the phosphorylation of CREB, and both gene expression and protein synthesis.5. Possible cellular and molecular events that do not require mRNA or protein synthesis should account for STM. These might include a hyperactivation of glutamate AMPA receptors, ribosome changes, or the exocytosis of glycoproteins that participate in cell addition.     

Repeated cerebral ischemia induced hippocampal cell death and impairments of spatial cognition in the rat

We developed a method of causing strong ischemic insult only in vulnerable nerve cells, such as hippocampal cells, without causing hemiplegia or difficulty in moving, by repeating cerebral ischemia for a brief time with a short interval periods. The rats subjected to 10 min of cerebral ischemia exhibited no impairment of spatial cognition at the test trial 7 days after final reperfusion. However, when the 10 min ischemia was repeated twice with a 1 hr interval, the rats exhibited a significant decrease in number of correct choices and increase in number of errors. Three times of repeated cerebral ischemia also induced a significant decrease in the number of correct choices and increase in the number of errors, but there were some rats showing motor difficulty. Cell death was typically observed in the CA1 layer of the hippocampus of rats subjected twice to 10 min of cerebral ischemia. Hippocampal and cortical acetylcholine (ACh) release weas transiently increased during the first and second 10 minutes of ischemia and normalized immediately after recirculation; thereafter, ACh release from these areas gradually decreased and showed a significantly low level at 7 days after recirculation. These results suggest that the repeated cerebral ischemia-induced impairment of spatial memory may be due to the dysfunction of hippocampal and cortical ACh systems and hippocampal cell death. The repeated cerebral ischemia model which produces cell death and ACh dysfunction in the hippocampus is thought to be useful for evaluating new drugs for the treatment of cerebrovascular dementia.     

Learning large-scale spatial relationships in a maze and effects of MK-801 on retrieval in the rhesus monkey

Monkeys have strong abilities to remember the visual properties of potential food sources for survival in the nature. The present study demonstrated the first observations of rhesus monkeys learning to solve complex spatial mazes in which routes were guided by visual cues. Three monkeys were trained in a maze (6 m x 6 m) included of four different mazes. We recorded the cue and cup errors, latencies, and pathway for each trial. The data showed that monkeys learned the target place after three days in the first maze and spent a shorter time in learning the following mazes. The maze was an efficient method to measure the ability and proceeding of spatial memory in monkeys. Moreover, working memory can also be tested by using the maze. MK-801 at 0.02 mg/kg but not at 0.005 mg/kg impaired monkeys' retrieval of spatial memory after they learned all four mazes. The present maze may provide an efficient method to help bridging the gap in cognition between nonhuman primates and humans, and in particular to gain insight into human cognitive function and dysfunction.     

Social context hinders humans but not ravens in a short-term memory task

Using resources shared within a social group—either in a cooperative or a competitive way—requires keeping track of own and others’ actions, which, in turn, requires well-developed short-term memory. Although short-term memory has been tested in social mammal species, little is known about this capacity in highly social birds, such as ravens. We compared ravens (Corvus corax) with humans in spatial tasks based on caching, which required short-term memory of one's own and of others’ actions. Human short-term memory has been most extensively tested of all social mammal species, hence providing an informative benchmark for the ravens. A recent study on another corvid species (Corvus corone) suggests their capacity to be similar to the humans’, but short-term memory skills have, to date, not been compared in a social setting. We used spatial setups based on caches of foods or objects, divided into individual and social conditions with two different spatial arrangements of caches (in a row or a 3 × 3 matrix). In each trial, a set of three up to nine caches was presented to an individual that was thereafter allowed to retrieve all items. Humans performed better on average across trials, but their performance dropped, when they had to keep track of partner's actions. This differed in ravens, as keeping track of such actions did not impair their performance. However, both humans and ravens demonstrated more memory-related mistakes in the social than in the individual conditions. Therefore, whereas both the ravens’ and the humans’ memory suffered in the social conditions, the ravens seemed to deal better with the demands of these conditions. The social conditions had a competitive element, and one might speculate that ravens’ memory strategies are more attuned to such situations, in particular in caching contexts, than is the case for humans.     

Would you say “yes” in the evening? Time-of-day effect on response bias in four types of working memory recognition tasks

Across a wide range of tasks, cognitive functioning is affected by circadian fluctuations. In this study, we investigated diurnal variations of working memory performance, taking into account not only hits and errors rates, but also sensitivity (d’) and response bias (c) indexes (established by signal detection theory). Fifty-two healthy volunteers performed four experimental tasks twice – in the morning and in the evening (approximately 1 and 10 h after awakening). All tasks were based on Deese–Roediger–McDermott paradigm version dedicated to study working/short-term memory distortions. Participants were to memorize sets of stimuli characterized by either conceptual or perceptual similarity, and to answer if they recognized subsequent stimulus (probe) as an “old” one (i.e. presented in the preceding memory set). The probe was of three types: positive, negative or related lure. In two verbal tasks, memory sets were characterized by semantic or phonological similarity. In two visual tasks, abstract objects were characterized by a number of overlapping similarities or differed in only one detail. The type of experimental material and the participants’ diurnal preference were taken into account. The analysis showed significant effect of time of day on false alarms rate (F_(1,50) = 5.29, p = 0.03, η_p² = 0.1) and response bias (F_(1,50) = 11.16, p = 0.002, η_p² = 0.18). In other words, in the evening participants responded in more liberal way than in the morning (answering “yes” more often). As the link between variations in false alarms rate, response bias and locus coeruleus activity was indicated in literature before, we believe that our data may be interpreted as supporting the hypothesis that diurnal fluctuations in norepinephrine release have effect on cognitive functioning in terms of decision threshold.     

P2Y6 receptor-dependent microglial phagocytosis of synapses mediates synaptic and memory loss in aging

Aging causes loss of brain synapses and memory, and microglial phagocytosis of synapses may contribute to this loss. Stressed neurons can release the nucleotide UTP, which is rapidly converted into UDP, that in turn activates the P2Y₆ receptor (P2Y₆R) on the surface of microglia, inducing microglial phagocytosis of neurons. However, whether the activation of P2Y₆R affects microglial phagocytosis of synapses is unknown. We show here that inactivation of P2Y₆R decreases microglial phagocytosis of isolated synapses (synaptosomes) and synaptic loss in neuronal–glial co-cultures. In vivo, wild-type mice aged from 4 to 17 months exhibited reduced synaptic density in cortical and hippocampal regions, which correlated with increased internalization of synaptic material within microglia. However, this aging-induced synaptic loss and internalization were absent in P2Y₆R knockout mice, and these mice also lacked any aging-induced memory loss. Thus, P2Y₆R appears to mediate aging-induced loss of synapses and memory by increasing microglial phagocytosis of synapses. Consequently, blocking P2Y₆R has the potential to prevent age-associated memory impairment.     

Increased daily handling of ovariectomized rats enhances performance on a radial-maze task and obscures effects of estradiol replacement

Estrogen impacts performance on tasks of learning and memory, although there are inconsistencies in the direction and magnitude of the reported effects. Contributory factors to the inconsistencies may be methodological differences associated with different regimens of treatment. The goal of the present experiment was to assess the effect of increased handling, such as that commonly associated with pharmacological or other experimental manipulations, on the ability of estrogen to influence working memory performance. Young adult rats were ovariectomized and implanted with capsules containing either cholesterol or 25% estradiol diluted in cholesterol. Half of each hormone treatment group received standard handling, which consisted of handling required to carry out experimental procedures and half received increased handling, which consisted of standard handling as well as 2 min of additional daily handling by the experimenter. Animals were trained daily on a working memory task on an eight-arm radial maze for 24 days of acquisition and for eight additional daily trials in which delays of either 1 min or 3 h were imposed between the fourth and fifth arm choices. Animals that received increased handling exhibited significantly enhanced performance during acquisition and delay trials compared to those that received standard handling. Estradiol significantly enhanced performance during delay trials in animals that received standard handling but had no effect in animals that received increased handling. These results suggest that the amount of handling that animals receive as part of experimental procedures may obscure the memory enhancing effects of estradiol replacement on certain tasks of cognition.     

RNA interference in hippocampus demonstrates opposing roles for CREB and PP1α in contextual and temporal long-term memory

We injected small interfering RNAs (siRNAs) directly into the hippocampus of wild-type mice, knocking down expression of cyclic AMP responsive element-binding protein (CREB) and disrupting long-term, but not short-term, memory after both contextual and trace fear conditioning. In contrast, similar knockdown of siRNA for protein phosphatase 1 (PP1) was sufficient to enhance contextual and temporal memory formation, thereby demonstrating with such a gain-of-function effect a lack of any general deleterious effect for this method of RNAi-mediated gene knockdown. Our findings clearly confirm that contextual memory formation involves CREB and PP1 as positive and negative regulators, respectively, and show for the first time that temporal memory formation shares this mechanism. More generally, we establish that direct injection of siRNA into identified adult brain regions yields specific gene knockdowns, which can be used to validate in vivo candidate genes involved in behavioral plasticity.     

Some characteristics of spatial associative memory in the pigeon, Columba livia

Willson and Wilkie (1993) developed a novel procedure to assess pigeons' memory for the spatial location of food. Only one of four locations provided food each daily session. Each location consisted of an illuminated pecking key and grain feeder. Over different days different locations, randomly selected, provided food during a 16-min session. The pigeons tended to revisit the location at which food was found on the previous day thereby demonstrating memory for food-spatial location associations over 24 h. Three experiments were conducted to further investigate this phenomenon. In Experiment 1 the session duration was varied between 4 and 32 min. Longer sessions had no detectable effect on their ability to remember the rewarded location 24 h later, a result that suggests that only brief encounters with food at a particular location are necessary for recall. In Experiment 2 the necessity of an active search for the day's rewarded location was removed; a 5-min period in which only the rewarded key was lit preceded the regular 16-min session. Pecks to the lit key in this 5-min period produced grain on the standard schedule. This manipulation facilitated the pigeons' discovery of food but did not affect their ability to remember the rewarded location, suggesting that the process of search and discovery is not essential to the associative memory process. In Experiment 3, food was available during the complete session (non-depleting condition) or was available only during the first half of the session (depleting condition). No detectable differences in the birds' memory of yesterday's profitable location were found. This suggests that non-depletion of food is not a necessary condition for day-to-day recall of food location. Taken together these findings enlarge our understanding of the spatial associative memory process.     

Long-term potentiation and olfactory memory formation in the carp (<Emphasis Type="Italic">Cyprinus carpio</Emphasis> L.) olfactory bulb

Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract—long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting <1 h) and post-tetanic potentiation (potentiation lasting <10 min); (2) Long-term potentiation was generally induced when both the dendrodendritic mitral-to-granule cell synapses and centrifugal fiber-to-granule cell synapses were repeatedly and simultaneously activated; (3) long-term enhancement (>1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).