Long-term retention of behavioural habituation in the rat

The orienting response in rats was measured by the interruption in licking that occurred during the presentation of a tone stimulus. Habituation occurred after a mean of 6·3 presentations and there was complete retention of habituation for 72 hr, and 70 per cent retention after 288 hr. This long-term storage involved in habituation distinguishes it from fatigue and supports the view that it must be regarded as a type of learning.     

Mollusk neuron habituation following extra- and intracellular administration of an ACTH fragment

By means of intracellular recording of the mollusc neuronal activity a study was made of the influence of ACTH4-7--a fragment of the stress hormone,--on elaboration of habituation to tactile stimuli. ACTH was administered immediately after the elaboration of the series I of habituation (25 to 30 stimuli) by means of either perfusion or extra- or intracellular microionophoresis. This was followed by the II-V habituation series (with 15 min intervals between them). Perfusion and extracellular (not intracellular) ACTH4-7 administration produced an acceleration of habituation in the series II, increase of action potentials (AP) thresholds in the response to the first tactile stimulus of series II and cessation of further increase of the AP thresholds in the course of elaboration. Without ACTH, these phenomena were observed beginning with habituation series IV. The ACTH action while influencing the memory is apparently directed to the external side of the excitable neuronal membrane; ACTH seems to accelerate the consolidation process. Any of the methods of ACTH administration produced also an enhancement of EPSPs and an increase in the number of APs in the responses to stimuli, without lowering the thresholds of APs generation. This testifies toi enhanced chemosensitivity of the membrane and may underlie the influence of ACTH on the level of wakefulness.     

Short-term and long-term habituation of exploration in rats,hamsters and gerbils

Short-term (within-session) and long-term (between-session) habituation of exploratory behavior was studied in rats, hamsters and gerbils. Subjects were observed in an open field containing four different objects during three 15-min sessions with an 8–14 h interval between each session. Their exploratory activity was measured by the numbers of contacts they made with these objects. The three species differed from each other in both their long-term and short-term habituation of exploration. Rats showed disrupted between-session habituation because of an important initial burst of activity at the beginning of each session. In contrast, hamsters and gerbils displayed between-session habituation, but within-session habituation occured during the first session only. These results are discussed in relation both to the adaptive value of exploration, and to the natural habitat of each species.     

Long-term retention of 133Ba in the rat trachea following local administration as barium sulfate particles

Long-term retention of 133Ba in the trachea from intratracheally administered BaSO4 particles was determined by both serial sacrifice and external scanning methods up to 6 months after injection. The amount of 133Ba retained 1 week after injection in the caudal region of the trachea, where the tip of the cannula had been at injection, was 0.41% of the initial dose. Thereafter the 133Ba was cleared exponentially with a mean half-time of 88 days, as determined from the autopsy samples. The cranial region of the trachea, including the site of the tracheostomy, contained 133Ba at 10 times the level in the caudal region 1 week after injection and was cleared with a half-time of 66 days. These clearance rates were confirmed by repeated external scanning over the trachea. The 133Ba was drained to the lymph nodes not only in the thoracic cavity but also in the cervical region, suggesting the possibility of lymphatic drainage from the trachea to the cervical lymph nodes.     

Metabolic heterogeneity of the proximal and distal kidney tubules

Proximal and distal tubule suspensions were prepared from kidneys of Sprague-Dawley rats by an isolation procedure on a Percoll^R gradient. The marker enzymes alkaline phosphatase (brush border) and hexokinase (cytoplasmic) as well as p-aminohippurate transport capacity, gluconeogenic activity and electron microscopy were used to characterize the two kidney tubule suspensions. The results of this study indicate that cytochrome P-450 is localized to the proximal tubular cells and that the O-deethylation of 7- ethoxycoumarin was higher in the proximal than distal fraction. Both proximal and distal tubules showed glucuronidation and deacetylation capacities and a relatively equal distribution of non-protein sulfhydryls. These studies demonstrate metabolic heterogeneity of the nephron, the proximal tubule being the main site of renal xenobiotic metabolism. Understanding of metabolic heterogeneity of proximal and distal kidney tubules should provide important information regarding cell specific mechanisms of nephrotoxicity.     

Relative variation in human proximal and distal limb segment lengths

The pattern of variation and covariation of proximal and distal limb segment lengths was examined within and between 20 geographically diverse skeletal samples of modern humans. Analyses of variance-covariance matrices (VCMs) of logarithmically transformed (ln) variates of humerus, radius, femur, and tibia length were performed to test the following hypotheses: first, within populations, the distal and proximal segments will have equal relative (i.e., size-independent) variability. However, between populations, the tibia is predicted to be more variable than the other segments. Tests of fit of computed VCMs to theoretical matrices by an iterative procedure (Anderson [1973] Ann. Stat. 1:135-141) reject the equal variance hypotheses, rather suggesting that the relative variances of the distal limb segments are greater than are those of the proximal. Males and females differ somewhat in that within females, the distal segments of both limbs have equal variance, while within males, the tibia has greater relative variance than the radius. The second hypothesis, regarding between-group variability, is somewhat supported in that between human populations, one cannot reject that the tibia has greater relative variance than the other limb segments. However, neither can one reject an alternative hypothesis that both distal limb segments (tibia and radius) are more variable than the proximal segments. Differential growth allometry is explored, and likely plays a major role in differences seen both within and between human populations.     

Modulation of synaptic plasticity in the hippocampus and piriform cortex by physiologically meaningful olfactory cues in an olfactory association task

Animals were trained to discriminate two natural odors while another group was trained to discriminate between a patterned electrical stimulation distributed on the lateral olfactory tract (LOT), labelled olfaco-mimetic stimulation (OMS), used as an olfactory cue versus a natural odor. No statistically significant difference was observed in behavioral data between these two groups. The animals trained to learn the meaning of the OMS exhibited a gradual long-term potentiation (LTP) phenomenon in the piriform cortex. When a group of naive animals was pseudo-conditioned, giving the OMS for the same number of sessions but without any olfactory training, no LTP was recorded. These results indicate that the process of learning olfactory association gradually potentiates cortical synapses in a defined cortical terminal field, and may explain why LTP in the piriform cortex is not elicited by the patterned stimulation itself, but only in an associative context. As olfactory and hippocampus regions are connected via the lateral entorhinal cortex, the olfactomimetic model was used to study the dynamic of involvement of the dentate gyrus (DG) in learning and memory of this associative olfactory task. Polysynaptic field potentials, evoked by the LOT stimulation, were recorded in the molecular layer of the ipsilateral DG. An early and rapid (2nd session) potentiation was observed when a significant discrimination of the two cues began to be observed. The onset latency of the potentiated response was 30–40 ms. When a group of naive animals was pseudoconditioned, no change was observed. Taken together, these results support the hypothesis that early activation of the DG during the learning of olfactory cue allows the progressive storage of olfactory information in a defined set of potentiated cortical synapses. The onset latency of the polysynaptic potentiated responses suggests the existence of a reactivating hippocampal loops during the processing of olfactory information.     

Long-term changes in neurotrophic factor expression in distal nerve stump following denervation and reinnervation with motor or sensory nerve

Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor nerve stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal nerve neurotrophic factor expression. We found that transected distal tibial nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neurotrophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal nerve stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory nerve (the cutaneous saphenous nerve) sutured to distal tibial nerve lowered injury-induced BDNF and GDNF mRNA levels in distal stump, but repair with a mixed nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed nerves did not affect nerve growth factor or neurotrophin-3 expression. Thus, distal nerve contributed to a neurotrophic environment for nerve regeneration for at least 6 months, and sensory nerve repair helped normalize distal nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory nerve.     

Effects of beta-carboline alkaloids on the object recognition task in mice

beta-carboline alkaloids are found in several medicinal plants and display a variety of actions on the central nervous, muscular and cardiovascular systems. The aim of the present study was to evaluate the effects of systemic administration of beta-carboline alkaloids on object recognition in mice. Adult Swiss mice received an intra-peritoneal injection (i.p.) of alkaloids (1.0, 2.5 or 5.0 mg/kg) 30 min before training in an object recognition task. The fully aromatic beta-carbolines, harmine and harmol, induced an enhancement of short-term memory (STM) at all doses tested when compared to controls. Harmaline, a dihydro beta-carboline and inverse agonist of the MK-801 binding site on the N-methyl-d-aspartate (NMDA) receptor, also induced an enhancement of both short-term memory (STM) and long-term memory (LTM). These results demonstrate that systemic administration of beta-carboline alkaloids can improve object recognition memory in mice.     

Dietary induction of angiotensin-converting enzyme in proximal and distal rat small intestine

Induction of angiotensin-converting enzyme was examined in proximal and distal intestinal segments of rats fed a low-protein (4%) diet and then switched to a high-protein (gelatin) diet. Animals were killed at varying time points, and brush-border membranes and total RNA were prepared from the segments. In the proximal intestine, there was a fivefold increase in angiotensin-converting enzyme levels after 14 days but only a twofold change in mRNA. In the distal intestine, there was no increase in enzyme activity but mRNA increased 2.4-fold. Organ culture was used to measure changes in enzyme biosynthesis. There was a 5- to 6-fold increase in the biosynthesis of angiotensin-converting enzyme in the proximal intestine 24 h after the switch to the gelatin diet and a 1.6-fold increase in mRNA levels. No change in biosynthesis was observed in the distal small intestine despite an increase in mRNA. These results support the conclusion that rapid dietary induction of intestinal angiotensin-converting enzyme is differentially regulated in proximal and distal segments of the small intestine.     

Long-term retention of surgically implanted radio transmitters in pikeperch

Radio-tagged pikeperch Stizostedion lucioperca (55–74 cm L _T) were recaptured in a reservoir by anglers 52–55 months after tagging. A total of four fish were recaptured during the summer of 2001. These recaptures are remarkable because of the long period between tagging and recapture and because only one (of 15 potential) tagged pikeperch had been caught in the long period since tagging.     

Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule

Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to <2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation.