Biomedical subjects

Uli Müller

Publications and source records attributed to Uli Müller.

10 recordsLinked to original sources

PubMed2006

Phase-dependent molecular requirements for memory reconsolidation: differential roles for protein synthesis and protein kinase A activity.

After consolidation, a process that requires gene expression and protein synthesis, memories are stable and highly resistant to disruption by amnestic influences. Recently, consolidated memory has been shown to become labile again after retrieval and to require a phase of reconsolidation to be preserved. New findings, showing that the dependence of reconsolidation on protein synthesis decreases with the age of memory, point to changing molecular requirements for reconsolidation during memory maturation. We examined this possibility by comparing the roles of protein synthesis (a general molecular requirement for memory consolidation) and the activation of protein kinase A (PKA) (a specific molecular requirement for memory consolidation), in memory reconsolidation at two time points after training. Using associative learning in Lymnaea, we show that reconsolidation after the retrieval of consolidated memory at both 6 and 24 h requires protein synthesis. In contrast, only reconsolidation at 6 h after training, but not at 24 h, requires PKA activity, which is in agreement with the measured retrieval-induced PKA activation at 6 h. This phase-dependent differential molecular requirement for reconsolidation supports the notion that even seemingly consolidated memories undergo further selective molecular maturation processes, which may only be detected by analyzing the role of specific pathways in memory reconsolidation after retrieval.

Animals↗

PubMed2005

Focal and temporal release of glutamate in the mushroom bodies improves olfactory memory in Apis mellifera.

In contrast to vertebrates, the role of the neurotransmitter glutamate in learning and memory in insects has hardly been investigated. The reason is that a pharmacological characterization of insect glutamate receptors is still missing; furthermore, it is difficult to locally restrict pharmacological interventions. In this study, we overcome these problems by using locally and temporally defined photo-uncaging of glutamate to study its role in olfactory learning and memory formation in the honeybee, Apis mellifera. Uncaging glutamate in the mushroom bodies immediately after a weak training protocol induced a higher memory rate 2 d after training, mimicking the effect of a strong training protocol. Glutamate release before training does not facilitate memory formation, suggesting that glutamate mediates processes triggered by training and required for memory formation. Uncaging glutamate in the antennal lobes shows no effect on memory formation. These results provide the first direct evidence for a temporally and locally restricted function of glutamate in memory formation in honeybees and insects.

Animals↗

PubMed2005

Use of an area index to retrospectively analyze the elimination of fox rabies in European countries.

Oral vaccination of foxes (OVF) is a powerful tool to combat rabies in wildlife, and large parts of western Europe have been freed from rabies using this tool. Nevertheless, the success of OVF, given with the number of campaigns needed to eliminate the disease, depends on many factors. This article for the first time focuses on and assesses difference in OVF with respect to the spatial setting of vaccinated areas with time. The size of the areas vaccinated with time and the size of the overlapping area of consecutively vaccinated areas are particularly considered. In order to integrate these two aspects into one single figure, an Area Index is proposed ranging between 0 and 1. A statistical analysis indicates that the number of campaigns needed for rabies elimination significantly decreases on condition that the total rabies endemic area is consecutively treated right from the beginning of oral vaccination. Hence, from an economical and environmental point of view, vaccination areas should be selected the way that guarantees an Area Index close to 1. The concept of an Area Index, as described here, is a useful tool not only in the context of OVF, but it could also be used for other control schemes against infectious diseases in wildlife.

Administration, Oral↗

PubMed2004

Synergistic activation of insect cAMP-dependent protein kinase A (type II) by cyclicAMP and cyclicGMP.

The high cGMP sensitivity of cAMP-dependent protein kinase A (type II) (PKAII) from invertebrates led to the hypothesis that cGMP directly activates PKAII under physiological conditions. We tested this idea using PKAII holoenzyme purified from the honeybee brain in an assay with short stimulation times. In the presence of very low cAMP concentrations, we found a synergistic increase in PKAII activation by physiological cGMP concentrations. Cloning honeybee regulatory subunit RII and phylogenetic comparison of the two cyclic nucleotide-binding sites of RII reveal a high relation of domain A of insect RII with cGMP-binding domains of cGMP-dependent protein kinases.

Animals↗

PubMed2004

Learning at different satiation levels reveals parallel functions for the cAMP-protein kinase A cascade in formation of long-term memory.

Learning and memory formation in intact animals is generally studied under defined parameters, including the control of feeding. We used associative olfactory conditioning of the proboscis extension response in honeybees to address effects of feeding status on processes of learning and memory formation. Comparing groups of animals with different but defined feeding status at the time of conditioning reveals new and characteristic features in memory formation. In animals fed 18 hr earlier, three-trial conditioning induces a stable memory that consists of different phases: a mid-term memory (MTM), translation-dependent early long-term memory (eLTM; 1-2 d), and a transcription-dependent late LTM (lLTM; > or =3 d). Additional feeding of a small amount of sucrose 4 hr before conditioning leads to a loss of all of these memory phases. Interestingly, the basal activity of the cAMP-dependent protein kinase A (PKA), a key player in LTM formation, differs in animals with different satiation levels. Pharmacological rescue of the low basal PKA activity in animals fed 4 hr before conditioning points to a specific function of cAMP-PKA cascade in mediating satiation-dependent memory formation. An increase in PKA activity during conditioning rescues only transcription-dependent lLTM; acquisition, MTM, and eLTM are still impaired. Thus, during conditioning, the cAMP-PKA cascade mediates the induction of the transcription-dependent lLTM, depending on the satiation level. This result provides the first evidence for a central and distinct function of the cAMP-PKA cascade connecting satiation level with learning.

Animals↗

PubMed2004

Assessing anti-rabies baiting--what happens on the ground?

BACKGROUND: Rabies is one of the most hazardous zoonoses in the world. Oral mass vaccination has developed into the most effective management method to control fox rabies. The future need to control the disease in large countries (i.e. Eastern Europe and the Americas) forces cost-benefit discussions. The 'Increase bait density' option refers to the usual management assumption that more baits per km2 could compensate for high fox abundance and override the imperfect supply of bait pieces to the individual fox. METHODS: We use a spatial simulation, which combines explicitly fox space use (tessellation polygons) and aeroplane flight lines (straight lines). The number of baits actually falling into each polygon is measured. The manager's strategic options are converted into changes of the resulting bait distribution on the ground. The comparison enables the rating of the options with respect to the management aim (i.e. accessibility of baits). RESULTS: Above 5% (approx. 10%) of all fox groups without any bait (at most 5 baits) relate to the baiting strategy applied in the field (1 km spaced parallel flight lines, 20 baits per km2 distributed) under habitat conditions comparable to middle and western Europe (fox group home-range 1 km2, 2.5 adults; reference strategy). Increasing the bait density on the same flight-line pattern neither reduces the number of under-baited fox group home-ranges, nor improves the management outcome and hence wastes resources. However, reducing the flight line distance provides a more even bait distribution and thus compensates for missed fox groups or extra high fox density.The reference strategy's bait density can be reduced when accounting for the missed fox groups. The management result with the proper strategy is likely the same but with reduced costs. CONCLUSION: There is no overall optimal strategy for the bait distribution in large areas. For major parts of the landscape, the reference strategy will be more competitive. In situations where set backs are attributed to non-homogeneous bait accessibility the distribution scheme has to be refined zone-based (i.e. increase of the flight line length per unit area). However, increase in bait density above the reference strategy appears inappropriate at least for non-urban abundance conditions of the red fox.

Administration, Oral↗

PubMed2003

Central modulatory neurons control fuel selection in flight muscle of migratory locust.

Insect flight is one of the most intense and energy-demanding physiological activities. High carbohydrate oxidation rates are necessary for take-off, but, to spare the limited carbohydrate reserves, long-distance flyers, such as locusts, soon switch to lipid as the main fuel. We demonstrate that before a flight, locust muscles are metabolically poised for take-off by the release of octopamine from central modulatory dorsal unpaired median (DUM) neurons, which increases the levels of the potent glycolytic activator fructose 2,6-bisphosphate in flight muscle. Because DUM neurons innervating the flight muscles are active during rest but selectively inhibited during flight, they stimulate carbohydrate catabolism during take-off but tend to decrease muscle glycolysis during prolonged flight. cAMP-dependent protein kinase A is necessary but not sufficient for signal transduction, suggesting parallel control via a calcium-dependent pathway. Locust flight is the first reported instance of a direct and specific involvement of neuronal activity in the control of muscle glycolysis in working muscle during exercise.

Animals↗

PubMed2002

Nitric oxide/cGMP-mediated protein kinase A activation in the antennal lobes plays an important role in appetitive reflex habituation in the honeybee.

Habituation, a form of non-associative learning, is observed throughout the animal kingdom. However, in contrast to associative learning, little is known about the underlying molecular mechanisms. Using the appetitive proboscis extension reflex in honeybees, we show that the cAMP-dependent protein kinase A (PKA) in the antennal lobe (AL) is implicated in the graded decline of behavioral response during habituation. Repeated stimulation leads to a slow and gradual increase in PKA activity superimposed on a fast transient PKA activation induced by each stimulus. These temporally distinct components of PKA activation are pharmacologically dissectible and are restricted to the AL on the stimulated side. Whereas the transient PKA activation induced by each stimulus requires monoaminergic transmission, the slow component of PKA activation is mediated by the nitric oxide (NO)/cGMP system. Local manipulation of the slow component of PKA activation in single ALs specifically interferes with the dynamic of habituation on the corresponding side. Our results provide strong evidence that NO/cGMP-mediated PKA activation in each AL contributes to temporal signal integration during habituation. Dishabituation by a sensory stimulus or spontaneous recovery from habituation does not require the PKA cascade. This provides evidence that the mechanisms underlying dishabituation and spontaneous recovery differ from those underlying temporal signal integration during habituation of the proboscis extension response.

Animals↗

PubMed2002

Hydroxyurea-induced partial mushroom body ablation in the honeybee Apis mellifera: volumetric analysis and quantitative protein determination.

Hydroxyurea (HU) treatment of first instar honeybee larvae was previously shown to cause mushroom body (MB) ablations. Predominantly, either one or both median MB subunits were ablated. This prompted us to analyze the effects of asymmetrical or symmetrical HU-induced MB ablation on both the morphology of the brain and on the level of three proteins (synapsin, PKA RII, and PKC), which are considered to play a role in synaptic plasticity, learning, and memory. In brains with one median MB subunit missing the volume of the overall MB calyx neuropil in the lesioned side was diminished by 35%. This strong reduction occurred although the remaining lateral MB calyx of the lesioned brain side was found to be significantly larger than that of the intact side. Accordingly, in brains with both median MB subunits missing the size of the remaining lateral calyces increased. The various types of MB ablation differentially affected the amounts of synapsin, PKA RII, and PKC expressed in the central brain. In animals with bilateral and thus symmetrical MB ablation (both median calyces ablated) the protein amount was found to be similar to that in control animals. However, unilateral MB ablation causes an increase in the amounts of the tested proteins in the intact brain side, while the levels in the ablated side were the same as in control animals. These findings not only show that HU-induced ablation of MB subunits is accompanied by volume changes and by changes in protein expression, but also suggest that these processes are highly regulated between the brain sides. The latter is of general importance in understanding the potential contribution of the MB subunits to learning and memory and their interaction between the brain sides.

Animals↗

PubMed2002

Learning in honeybees: from molecules to behaviour.

Studies in a variety of organisms as diverse as molluscs, insects, birds and mammals have shown that memories can exist in a variety of temporal domains ranging from short-term memories in the range of minutes to long-term memories lasting a lifetime. While transient covalent modifications of proteins underlie short-term memory, the formation of long-term memory requires gene expression and protein synthesis. Different intracellular signalling cascades have been implicated in distinct aspects of learning and memory formation. Little is known however, about how learning in intact animals is related to the modulation of these signalling cascades and how this contributes to distinct neuronal and behavioural changes in vivo. Associative learning in the honeybee provides the opportunity to study processes of memory formation by analysing its progression through different phases, across levels of behaviour, neural circuits, and cellular signalling pathways. The findings reveal evidence that various cellular signalling pathways in the neuronal circuit of distinct brain areas play a role in different processes during learning and memory formation.

Journal Article↗