Overview of Research in the Lindgren Lab
See the projects page to learn about our ongoing research projects.
We study synapses, where neurons communicate with other neurons or muscle cells.
(Left) This confocal microscope image shows the branching of the nerve terminal and surrounding myelin in blue staining. The location of ACh receptors on the nerve terminal is indicated by red staining.
(Right) In this confocal image, the nerve terminal and myelin are stained in green, and ACh receptors are denoted by the red staining.
In both cases, the imaging was done on live, unfixed mouse muscle tissue using a 40x water immersion objective, and were deconvolved to remove noise. For those interested in the details, the nerve and myelin were stained with FM1-43, a styrl dye that is attracted to cell membranes and becomes concentrated in the nerve terminal by compensatory endocytosis following the evoked exocytosis of synaptic vesicles. The ACh receptors are stained by alpha-bungarotoxin conjugated to the Alexa Fluor 555.
Since 2020, we have been focused on a form of synaptic plasticity (i.e. synaptic change) called presynaptic homeostatic potentiation (PHP). This refers to the ability of many synapses, especially the NMJ, to compensate for disruptions in the activation of the receptors on the postsynaptic cell by increasing the amount of neurotransmitter released by the presynaptic cell. Despite having known about this phenomenon for almost 50 years, the signal responsible for telling the neuron to release more neurotransmitter has remained a mystery.
Presynaptic Homeostatic Potentiation (PHP). Applying d-Tubocurarine Chloride (dTC) to block approximately half of the nAChRs results in an initial decrease in mEPPs (caused by the spontaneous release of ACh from a single synaptic vesicle) and EPPs (caused by the induced release of multiple synaptic vesicles following an action potential in the motor nerve). A signal is presumably generated by the muscle which feeds back to the nerve terminal (arrow and ?), and leads to increasing quantal neurotransmitter release (QC), restoring the EPP towards its original level (right panel).
We have conducted experiments suggesting that the simplest molecule in the universe, the hydrogen ion (just a mere proton +), communicates from the muscle back to the nerve and triggers PHP. We have published two papers supporting this novel hypothesis and are actively seeking insight into the underlying mechanisms.
The specific projects we are currently working on are described under Projects.