BMAA (beta-methylamino alanine) is an environmental neurotoxin that is suspected to be a glutamate agonist. Previous studies have shown that glutamate is an excitatory neurotransmitter in the neuromuscular junctions of insects and a neuromodulator in the central nervous system (affecting the central pattern generator for motor output). To explore the possible glutamate-agonist action of BMAA, we fed BMAA to adult fruit flies and quantified their locomotor behavior. We fed BMAA at three different concentrations for four consecutive days and recorded the flies’ behavior for 10 minutes each day. Below are trajectories of individual flies in lenticular arenas, as a function of dosage and time. Black trax represent the floor of the dish, and red represents the ceiling.
We observed that flies
treated with the two lowest concentrations of BMAA walk faster and
spend more time walking. The treated flies do not walk more often
(which would correspond to shorter bouts of inactivity), but their
walking bouts last longer than those of the control flies. These
observations are consistent with BMAA acting as a glutamate agonist in
the central complex, one that excites the central pattern
Previous studies on the temporal structure of walking behavior in fruit
flies suggest that the central pattern generator regulates the inactive
phase rather than the walking phase of activity periods. Such a
control system should respond to BMAA with a shortening of the inactive
period and leave the walking period unaffected. This prediction
is not consistent with our observations of flies treated with the two
low BMAA concentrations. At the highest concentration of BMAA,
the flies show severe symptoms: they walk much less than the control
group, exhibit tremors, and experience difficulty standing and righting
themselves after falling.
We are currently exploring why BMAA seems to have a stronger effect on the central pattern generator in the central nervous system than on the neuromuscular junctions and the peripheral nervous system.
A traditional test of fruit-fly motor ability is the climb up a
vertical wall. We record this instincitve behavior
(following a tap-down) in PMMA cuvettes, with treated flies and
controls side by side:
As flies climb up the wall, the 'triangles of support' are digitized step by step:
Not surprisingly, we fnd that flies treated with BMAA stumble more often. We are currrently studying the footfall patterns of treated fruit flies to explore how this glutamate agonist affects walking behavior. Preliminar data suggest that BMAA causes the feet to be place closer to the body, reducing the triangle of support and thereby reducing stability.