Roland Strauss

The central complex and the genetic dissection of locomotor behaviour.

The central complex is one of the most prominent, yet functionally enigmatic structures of the insect brain. Recently, behavioural, neuroanatomical and molecular approaches in Drosophila have joined forces to disclose specific components of higher locomotion control in larvae and adult flies, such as those that guarantee the optimal length and across-body symmetry of strides and an appropriate activity.

Analysis of a spatial orientation memory in Drosophila.

Flexible goal-driven orientation requires that the position of a target be stored, especially in case the target moves out of sight. The capability to retain, recall and integrate such positional information into guiding behaviour has been summarized under the term spatial working memory. This kind of memory contains specific details of the presence that are not necessarily part of a long-term memory. Neurophysiological studies in primates indicate that sustained activity of neurons encodes the sensory information even though the object is no longer present. Furthermore they suggest that dopamine transmits the respective input to the prefrontal cortex, and simultaneous suppression by GABA spatially restricts this neuronal activity. Here we show that Drosophila melanogaster possesses a similar spatial memory during locomotion. Using a new detour setup, we show that flies can remember the position of an object for several seconds after it has been removed from their environment. In this setup, flies are temporarily lured away from the direction towards their hidden target, yet they are thereafter able to aim for their former target. Furthermore, we find that the GABAergic (stainable with antibodies against GABA) ring neurons of the ellipsoid body in the central brain are necessary and their plasticity is sufficient for a functional spatial orientation memory in flies. We also find that the protein kinase S6KII (ignorant) is required in a distinct subset of ring neurons to display this memory. Conditional expression of S6KII in these neurons only in adults can restore the loss of the orientation memory of the ignorant mutant. The S6KII signalling pathway therefore seems to be acutely required in the ring neurons for spatial orientation memory in flies.

Goal-Driven Behavioral Adaptations in Gap-Climbing Drosophila

Tasks such as reaching out toward a distant target require adaptive and goal-oriented muscle-activity patterns. The CNS likely composes such patterns from behavioral subunits. How this coordination is done is a central issue in neural motor control. Here, we present a novel paradigm, which allows us to address this question in Drosophila with neurogenetic tools. Freely walking flies are faced with a chasm in their way. Whether they initiate gap-crossing behavior at all and how vigorously they try to reach the other side of the gap depend on a visual estimate of the gap width. By interfering with various putative distance-measuring mechanisms, we found that flies chiefly use the vertical edges on the targeted side to distill the gap width from the parallax motion generated during the approach. At gaps of surmountable width, flies combine and successively improve three behavioral adaptations to maximize the front-leg reach. Each leg pair contributes in a different manner. A screen for climbing mutants yielded lines with defects in the control of climbing initiation and others with specific impairments of particular behavioral adaptations while climbing. The fact that the adaptations can be impaired separately unveils them as distinct subunits.

Photodynamic therapy using aminolaevulinic acid does not lead to clinical improvement in hidradenitis suppurativa

SIR, Hidradenitis suppurativa (HS) is a chronic, inflammatory, scarring disease of the apocrine sweat gland-bearing skin. The primary event in the development of abscesses and sinus tracts is follicular occlusion caused by keratinized, stratified squamous epithelium, with the apocrine glands becoming involved only at a later stage. Treatment approaches are similar to those in acne vulgaris, including topical and systemic antibiotics, hormonal therapy and oral retinoids. Phototherapy with a combination of blue (415 nm) and red (660 nm) light was found significantly to reduce the number of comedones in patients with acne. In addition, photodynamic therapy (PDT) using aminolaevulinic acid (ALA) has been shown to be an effective treatment in acne vulgaris. A study by Hongcharu et al. has provided some evidence to support a reduction of follicular obstruction through changes in keratinocyte shedding and hyperkeratosis as a possible mechanism of action of ALA-PDT in acne, although much higher fluences of light were used in this compared with previous studies. Under the hypothesis that treatment with ALA-PDT could reduce the number of comedonal lesions and subsequently of inflammatory lesions in patients with HS, we performed an open pilot study investigating the effect of ALA-PDT in HS. Local Ethics Committee approval was obtained. Endpoints were defined as significant improvement not requiring any further treatment (agreed by both patient and observer) or three completed treatments, whichever came first. Patients with axillary or groin disease were eligible for enrolment. The severity of the condition was assessed by a scoring system as described by Sartorius et al. as well as with visual analogue scales recording the degree of disease activity and pain as perceived by the patient. The site with the highest HS regional score (groin or axilla) was chosen for treatment. ALA was applied locally (20% in Unguentum; Merck, Darmstadt, Germany) and occluded for 4 h. The treatment area was then anaesthetized by infiltration of local anaesthetic (1% lignocaine), followed by treatment with the therapeutic light source, the Ceramoptec diode laser (633 nm) in three patients and a broadband red light source, CureLight lamp (570–670 nm) in one patient. A total dose of 15 J cm was applied per treatment. A maximum of three treatments at weekly intervals was given, depending on the response. Assessments were performed pretreatment, 1 week following each treatment and 8 weeks after the last treatment. Results are shown in Table 1. Four patients were enrolled, three with axillary disease and one with groin disease. Two patients reached an endpoint: one patient completed three treatments (patient 1), and the other noticed a significant improvement after two treatments, and no more treatments were therefore given (patient 2). At 8-week follow-up, however, the regional HS score had improved only marginally in one patient but had worsened in the other patient compared with baseline values. Of the two patients who did not complete the study, one received only one treatment and then decided against further treatments because of severe burning and stinging (patient 3). The fourth patient had two treatments and then decided against continuing therapy as the condition appeared to worsen (patient 4). Again, regional HS scores at follow-up in both patients did not show any improvement, but marked deterioration in one patient (patient 4).

Persistence of orientation toward a temporarily invisible landmark in Drosophila melanogaster.

Abstract In arena experiments with the walking fruit fly, we found a remarkable persistence of orientation toward a landmark that disappeared during the flys approach. The directional stability achieved by `after-fixation allows a fly to continue pursuit under natural conditions, where a selected target is frequently concealed by surrounding structures. The persistence of after-fixation was investigated in Buridans paradigm, where a fly walks persistently back and forth between two inaccessible landmarks. Upon disappearance of a selected target, the flies maintained their intended course for more than 15 body lengths of approximately 2.5 mm in about 50% of the trials. About 13% even exceeded 75 body lengths. About 88% of the approaches clustered in equal portions around peaks at 2.4u2009s and 8.6u2009s. About 12% of the approaches persisted even longer. In contrast, a single peak at about 2.2u2009s is sufficient to describe the persistence of orientation in a random walk. The ability to pursue an invisible landmark is disturbed neither by a transient angular deviation from the course toward this landmark, when this target disappeared, nor by a distracting second landmark. Accordingly, after-fixation seems to require an internal representation of the direction toward the concealed target, and idiothetical course control to maintain this direction.

Visual Targeting of Motor Actions in Climbing Drosophila

Drosophila melanogaster flies cross surmountable gaps in their walkway of widths exceeding their body length with an astounding maneuver but avoid attempts at insurmountable gaps by visual width estimation. Different mutant lines affect specific aspects of this maneuver, indicating a high complexity and modularity of the underlying motor control. Here we report on two mutants, ocelliless(1) and tay bridge(1), that, although making a correct decision to climb, fail dramatically in aiming at the right direction. Both mutants show structural defects in the protocerebral bridge, a central complex neuropil formed like a handlebar spanning the brain hemispheres. The bridge has been implicated in step-length control in walking flies and celestial E-vector orientation in locusts. In rescue experiments using tay bridge(1) flies, the integrity of the bridge was reestablished, concomitantly leading to a significant improvement of their orientation at the gap. Although producing directional scatter, their attempts were clearly aimed at the landing site. However, this partial rescue was lost in these flies at a reduced-visibility landing site. We therefore conclude that the protocerebral bridge is an essential part of a visual targeting network that transmits directional clues to the motor output via a known projection system.

Virtual-Reality Techniques Resolve the Visual Cues Used by Fruit Flies to Evaluate Object Distances

Insects can estimate distance or time-to-contact of surrounding objects from locomotion-induced changes in their retinal position and/or size. Freely walking fruit flies (Drosophila melanogaster) use the received mixture of different distance cues to select the nearest objects for subsequent visits. Conventional methods of behavioral analysis fail to elucidate the underlying data extraction. Here we demonstrate first comprehensive solutions of this problem by substituting virtual for real objects; a tracker-controlled 360 degrees panorama converts a fruit flys changing coordinates into object illusions that require the perception of specific cues to appear at preselected distances up to infinity. An application reveals the following: (1) en-route sampling of retinal-image changes accounts for distance discrimination within a surprising range of at least 8-80 body lengths (20-200 mm). Stereopsis and peering are not involved. (2) Distance from image translation in the expected direction (motion parallax) outweighs distance from image expansion, which accounts for impact-avoiding flight reactions to looming objects. (3) The ability to discriminate distances is robust to artificially delayed updating of image translation. Fruit flies appear to interrelate self-motion and its visual feedback within a surprisingly long time window of about 2 s. The comparative distance inspection practiced in the small fruit fly deserves utilization in self-moving robots.

Spontaneous involution of congenital melanocytic nevi of the scalp

Large or giant congenital melanocytic nevi are rare. They are associated with a risk of melanoma, which is poorly quantified, and often represent a major cosmetic problem. Surgical intervention is the most common treatment, although dermabrasion or curettage in the first weeks of life is used in some centers. When these nevi occur in the scalp, the risk of melanoma has been reported to be lower. Here we describe a series of children in whom large congenital melanocytic nevi on the scalp appeared to spontaneously involute. Therefore, our findings indicate that these nevi also have a better prognosis cosmetically. It is suggested that the decision about surgical treatment should be deferred until the maximal improvement in appearance has occurred during the first 2 years of life.

Occupational contact dermatitis in nurses with hand eczema.

Occupationally related dermatitis is a common problem in nurses, who are exposed to a wide variety of allergenic and irritant substances. In a group of 44 nurses with hand dermatitis (40 female, 4 male), 18 were thought to have a predominantly allergic contact dermatitis, 15 an irritant dermatitis, 7 other form of eczema, 3 atopic dermatitis and one pompholyx. 10 of the 15 irritant cases were diagnosed as occupational. Of the 18 patients with allergic contact dermatitis, the allergens were thought to be occupationally relevant in 8 cases. In 6 of these 8 the dermatitis was due to natural rubber latex (3) or other rubber chemicals (3). 2 had additional evidence of immediate‐type hypersensitivity to natural rubber latex (one was patch test allergic to latex, the other to thiuram mix). Natural rubber latex allergy, both delayed and immediate, is a significant problem, and nurses at risk should be tested for both types of hypersensitivity, as well as being patch tested to standard, rubber and medicaments series.

The visual orientation memory of Drosophila requires Foraging (PKG) upstream of Ignorant (RSK2) in ring neurons of the central complex.

Orientation and navigation in a complex environment requires path planning and recall to exert goal-driven behavior. Walking Drosophila flies possess a visual orientation memory for attractive targets which is localized in the central complex of the adult brain. Here we show that this type of working memory requires the cGMP-dependent protein kinase encoded by the foraging gene in just one type of ellipsoid-body ring neurons. Moreover, genetic and epistatic interaction studies provide evidence that Foraging functions upstream of the Ignorant Ribosomal-S6 Kinase 2, thus revealing a novel neuronal signaling pathway necessary for this type of memory in Drosophila.