Synaptic transmission: mechanisms and modulation

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Our research uses a variety of "model" synapses, chosen for their advantageous physiology, anatomy or distinct release or plasticity properties, to explore neurotransmission and its regulation by activity or neuromodulators. Our NSERC supported studies address fundamental questions of neuronal communication and they have application to practical problems. Precise control of the amount and timing of release is needed for neural circuits to function properly. Changes in connection strength underly many neural processes as simple as adaptation to constant stimuli or complicated as learning and memory and many neurological and neuromuscular disorders are caused by dysfunctional synaptic communication. We therefore need to understand synaptic transmission to decipher normal brain function and to rationally design therapeutic strategies for neurological disorders. Previous NSERC funded work compared activity dependent plasticity of olfactory to mitral cell synapses in the main olfactory bulb (MOB), to plasticity of vomeronasal to accessory OB (AOB). We showed how their particular activity dependent properties (depressing-MOB; facilitating-AOB) adapt them to the different sensory reception and processing tasks performed by these parallel odor-processing circuits. For example, transmission from mitral to AOB synapses is enhanced for >10 seconds after stimulation of one or a few successive presynaptic action potentials making them exceptional integrators of low frequency activity. We will extend this descriptive work in the next cycle by investigating the biochemical mechanism underlying this unique form of long term "facilitation" (so termed because it only requires a few stimuli to induce it). During the last grant cycle we also described potentiation of AOB to amygdala synapses that is distinctive for the long duration of potentiated release (both a PTP >10 mins and LTP, > 1 hour) that is produced by small amount of low frequency stimulation that can induce it (e.g. <1 min at 5 Hz). The next grant cycle will focus on elucidating the mechanisms by which these synapses implement these forms of activity dependent plasticity and how neuromodulation of presynaptic terminal function by muscarinic acetylcholine receptors affects the induction and maintenance of plasticity. Recycling of vesicles after release is essential to maintain transmission during sustained activation.  We will extend our previous studies that used fluorescent styryl dyes and electron microscopy to locate recycling vesicles at the crayfish neuromuscular junction through a collaboration with van Veggel (UvIC, chemistry) that will utilize trapping of luminescent nanoparticles during vesicle endocytosis. These studies will address hypotheses pertaining to the pathways by which recycled membrane is turned into functional docked transmitter vesicles, important information to obtain since many neurological (particularly neuromuscular) disorders can be traced to poor vesicle recycling.