Carbamates, atropine, and diazepam: effects on performance in the running rat

We have reported that when rats (500 g, male) are exercised to exhaustion on a treadmill, pretreatment with the centrally acting carbamate physostigmine reduced endurance (run time, RT) and increased the rate of rise of core temperature (Tc+). Both RT and Tc+ were restored to control levels by pretreatment with either or a combination of atropine (A), and diazepam (D). Our objective in the present work was to determine whether A+D could also restore the performance and thermoregulatory decrements induced by the peripherally acting carbamate pyridostigmine (PY). After drug administration, rats were run (11 m/min, 6 degrees elevation, Ta = 26 degrees C) to exhaustion. PY treatment resulted in a reduced RT and an increased heat gain that neither A nor D alone (A+PY and D+PY) could restore to control levels. On the other hand, a combination of both A and D restored these variables to control levels. In conclusion, A+D can restore the performance and thermoregulatory decrements resulting from the administration of either a centrally or a peripherally acting carbamate.     

Small-scale spatial distribution of marine meiobenthos: the effects of decaying macrofauna

Summary To evaluate the effects of decaying animals on small-scale horizontal distribution of meiobenthos in muddy habitats, a laboratory experiment was performed at the Askö Laboratory in the northwestern Baltic Sea. A microcosm (35×55×28 cm) containing a ca. 7-cm thick layer of sieved (0.5 mm) sublittoral mud was established in June 1990. Three months later specimens of the bivalve Macoma balthica were collected and killed in boiling water. The sediment inside the microcosm was implanted with empty shell, empty shell and dead animal or left alone. At the end of the experiment (17 days) visual examination of the microcosm revealed black spots at the sediment surface where dead animals had been implanted. The densities of nematodes, the most abundant group (98%), were not significantly different between areas. However total non-nematode fauna was found in much lower numbers (P<0.01) in the black spot areas. A multivariate analysis (detrended correspondence ordination) of nematode species abundance data separated samples from the black spot areas from the others. Of the 25 nematode species recorded in the microcosm, there was a significant difference between areas for four species. The decaying animals clearly attracted Monhystera disjuncta which was almost 6 times as abundant in the black spot areas compared to control and shell areas. Both the overall dominant species, Leptolaimus elegans and Calomicrolaimus honestus were found in lower numbers in the areas of dead Macoma than in control and shell areas. Sabatieria pulchra was found in lower numbers in the control areas compared to shell and dead animal areas. The overall structure of the nematode assemblage indicated a shift to lower dominance in the dead animal areas and it is speculated that decomposing animal tissue may be of primary importance regarding spatial distribution of meiobenthos.     

Psychoacoustic tests: effects of atropine]

The efferent pathways exert a control action on the function of the cochlear nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal system and its action can be blocked by atropine. In order to give a contribution to the knowledge of the function of the efferent bundle and of the cochlea efficiency we examined 10 young normal subjects before and after infusion of 1 mg of atropine i.v. a battery of three psychoacoustical tests (Remote Masking, Critical Ratio and Brief Tone Audiometry). After infusion of atropine we have shown an increase of 0.25 Hz hearing threshold, an increase of RC values and a decrease of RM values. It can be concluded that the pharmacological block of the olivo-cochlear bundle determines a stiffness of outer hair cells and basilar membrane; this finding means that the atropine can inhibit the facilitating activity of the efferent system on the cochlear performance.     

Evoked acoustic oto-emissions: effects of atropine

The Evoked Otoacoustic Emissions (EOE) are a sinusoidal wave complex coming from the contractile properties of the cochlea and particularly of the outer hair cells. This activity is influenced by the centrifugal pathways whose transmitter is acetylcholine. In order to study the effects of the functional block of the cochlea, ten young normal subjects were examined recording the EOE before and ten mins after the i.v. infusion of 1 mg of atropine. The statistical analysis of the results has shown a significant decrease only in EOE appearance threshold in absence of modifications of the saturation level. These data have led us to believe that atropine blocking of the centrifugal pathways causes a disfunction of the outer hair cells that accept less energy to be transduced into a neural stimulus and on the other hand more energy as EOEs.     

The hippocampus, spatial memory and food hoarding: a puzzle revisited

Behavioural ecology assumes that cognitive traits and their underlying neural substrates are shaped by natural selection in much the same way as morphological traits are, resulting in adaptation to the natural environment of the species concerned. Recently, however, the 'neuroecology' approach of attempting to gain insight into brain structure and function by testing predictions about variation in brain structure based on knowledge of the lifestyle of the animal has been criticized on the grounds that such an adaptationist view cannot provide insight into the underlying mechanisms. Furthermore, the criticism has focussed on attempts to use variation in demand for spatial memory and in hippocampal size as a basis for predicting variation in cognitive abilities. Here, we revisit this critique against the field of so-called 'neuroecology' and argue that using knowledge of the natural history of animals has lead to a better understanding of the interspecific variation in spatial abilities and hippocampal size, and to the generation of novel hypotheses and predictions.     

Anti-androgenic effects of bisphenol-A on spatial memory and synaptic plasticity of the hippocampus in mice

Bisphenol-A (BPA) is a common environmental endocrine disruptor. Our recent studies found that exposure to BPA in both adolescent and adulthood sex-specifically impaired spatial memory in male mice. In this study, 11-week-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.4 and 4 mg/kg), or vehicle for 45 days. The results of Morris water maze task showed that exposure to BPA did not affect the spatial memory of GDX mice but impaired that of sham (4 mg/kg/day) and TP-treated GDX mice (0.4 mg/kg/day). In addition, BPA reduced the level of testosterone (T) in the serum and brain of sham and TP-treated GDX mice. Exposure to BPA decreased the synaptic density and had an adverse effect on the synaptic interface of the hippocampus in sham and TP-treated GDX mice. The results of western blot analysis further showed that BPA (4 mg/kg) reduced the levels of synaptic proteins (synapsin I and PSD-95) and NMDA receptor subunit NR2B in sham and TP-treated GDX mice. BPA decreased the phosphorylation of ERK1/2 but increased the phosphorylation of p38 in sham and TP-treated GDX mice. These results suggest that impairment of spatial memory and adverse effects on synaptic remodeling of hippocampal neurons in males after long-term BPA exposure is related to the anti-androgen effect of BPA. These effects of BPA may be associated with downregulated synaptic proteins and NMDA receptor through inhibiting ERKs and promoting the p38 pathways.     

The spatial distribution of flocking foragers: disentangling the effects of food availability,interference and conspecific attraction by means of spatial autoregressive modeling

Patch choice of foraging animals is typically assumed to depend positively on food availability and negatively on interference while benefits of the co‐occurrence of conspecifics tend to be ignored. In this paper we integrate a classical functional response model based on resource availability and interference with a conspecific attraction model and use it to simulate spatial distributions of animals in their continuous resource landscapes. We consider both equilibrium and non‐equilibrium distributions. We show that the integrated model produces distributions of foraging animals that closely match the distributions observed in nature. The simulations also show that under information uncertainty the locations of flocks are highly variable when conspecific attraction is strong. We furthermore explain how we can estimate the impacts of conspecific attraction and interference on the distribution of foraging animals by spatial autoregression. On the basis of simulated data we show that the separate impacts of interference and conspecific attraction can be disentangled when prior information on either is available, in addition to information on resource density and predator density, and that the total food effect is given by the spatial multiplier.     

Computation of spiking activity for a stochastic spatial neuron model: effects of spatial distribution of input on bimodality and CV of the ISI distribution

We obtain computational results for a new extended spatial neuron model in which the neuronal electrical depolarization from resting level satisfies a cable partial differential equation and the synaptic input current is also a function of space and time, obeying a first order linear partial differential equation driven by a two-parameter random process. The model is first described explicitly with the inclusion of all biophysical parameters. Simplified equations are obtained with dimensionless space and time variables. A standard parameter set is described, based mainly on values appropriate for cortical pyramidal cells. When the noise is small and the mean voltage crosses threshold, a formula is derived for the expected time to spike. A simulation algorithm, involving one-dimensional random processes is given and used to obtain moments and distributions of the interspike interval (ISI). The parameters used are those for a near balanced state and there is great sensitivity of the firing rate around the balance point. This sensitivity may be related to genetically induced pathological brain properties (Rett's syndrome). The simulation procedure is employed to find the ISI distribution for some simple patterns of synaptic input with various relative strengths for excitation and inhibition. With excitation only, the ISI distribution is unimodal of exponential type and with a large coefficient of variation. As inhibition near the soma grows, two striking effects emerge. The ISI distribution shifts first to bimodal and then to unimodal with an approximately Gaussian shape with a concentration at large intervals. At the same time the coefficient of variation of the ISI drops dramatically to less than 1/5 of its value without inhibition.     

The hippocampus and memory: insights from spatial processing

The hippocampus appears to be crucial for long-term episodic memory, yet its precise role remains elusive. Electrophysiological studies in rodents offer a useful starting point for developing models of hippocampal processing in the spatial domain. Here we review one such model that points to an essential role for the hippocampus in the construction of mental images. We explain how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discuss its broader implications for the neural bases of episodic memory.     

Brain-stem auditory pathways: effects of atropine]

The efferent pathways exert a control action on the function of the cochlear nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal system and its action can be blocked by Atropine. In order to give a contribution to the knowledge of the function of the efferent bundle, Auditory Brainstem Responses (ABRs) and Acoustic Reflex Latencies (ARLs) have been examined in 10 young normal subjects there was also a decrease in latency greater than or equal to 100 microseconds by at least other two waves. The only statistically significant difference was relative to the latency mean value of the wave III recorded in contralateral derivation at 11 pps. The ARLs, after the infusion of atropine, showed a statistically significant increase in 7 of the 10 cases; no change was recorded in the AR amplitude. It can be concluded that the pharmacological block of the olivo-cochlear bundle determines a delay in the neural conduction of the acoustic impulses; this finding means that the atropine can inhibit the facilitating activity of the efferent system on the brainstem afferent pathways.     

Acute and chronic effects of glucose and carbachol on insulin secretion and phospholipase C activation: studies with diazoxide and atropine

The acute and chronic effects of 20 mM glucose and 10 microM carbachol on beta-cell responses were investigated. Acute exposure of rat islets to 20 mM glucose increased glucose usage rates and resulted in a large insulin-secretory response during a dynamic perifusion. The secretory, but not the metabolic, effect of 20 mM glucose was abolished by simultaneous exposure to 100 microM diazoxide. Glucose (20 mM) significantly increased inositol phosphate (IP) accumulation, an index of phospholipase C (PLC) activation, from [(3)H]inositol-prelabeled islets. Diazoxide, but not atropine, abolished this effect as well. Unlike 20 mM glucose, 10 microM carbachol (in the presence of 5 mM glucose) increased IP accumulation but had no effect on insulin secretion or glucose (5 mM) metabolism. The IP effect was abolished by 50 microM atropine but not by diazoxide. Chronic 3-h exposure of islets to 20 mM glucose or 10 microM carbachol profoundly reduced both the insulin-secretory and PLC responses to a subsequent 20 mM glucose stimulus. The adverse effects of chronic glucose exposure were abolished by diazoxide but not by atropine. In contrast, the adverse effects of carbachol were abolished by atropine but not by diazoxide. Prior 3 h of exposure to 20 mM glucose or carbachol had no inhibitory effect on glucose metabolism. Significant secretory responses could be evoked from 20 mM glucose- or carbachol-pretreated islets by the inclusion of forskolin. These findings support the concept that an early event in the evolution of beta-cell desensitization is the impaired activation of islet PLC.     

Functional effects of somatostatin receptor 1 activation on synaptic transmission in the mouse hippocampus

Somatostatin‐14 (SRIF) co‐localizes with GABA in the hippocampus and regulates neuronal excitability. A role of SRIF in the control of hippocampal activity has been proposed, although the exact contribution of each SRIF receptor (sst₁–sst₅) in mediating SRIF action requires some clarification. We used hippocampal slices of wild‐type and sst₁ knockout (KO) mice and selective pharmacological tools to provide conclusive evidence for a role of sst₁ in mediating SRIF inhibition of synaptic transmission. With single‐ and double‐label immunohistochemistry, we determined the distribution of sst₁ in hippocampal slices and we quantified sst₁ colocalization with SRIF. With electrophysiology, we found that sst₁ activation with CH‐275 inhibited both the NMDA‐ and the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐mediated responses. Results from sst₁ KO slices confirmed the specificity of CH‐275 effects; sst₁ activation did not affect the inhibitory transmission which was in contrast increased by sst₄ activation with L‐803,087 in both wild‐type and sst₁ KO slices. The AMPA‐mediated responses were increased by L‐803,087. Functional interaction between sst₁ and sst₄ is suggested by the finding that their combined activation prevented the CH‐275‐induced inhibition of AMPA transmission. The involvement of pre‐synaptic mechanisms in mediating inhibitory effects of sst₁ on excitatory transmission was demonstrated by the finding that CH‐275 (i) increased the paired‐pulse facilitation ratio, (ii) did not influence the AMPA depolarization in the presence of tetrodotoxin, and (iii) inhibited glutamate release induced by epileptiform treatment. We conclude that SRIF control of excitatory transmission through an action at sst₁ may represent an important contribution to the regulation of hippocampal activity.