How is long-distance transport of AMPA receptors regulated?

Coni Stacher Hoerndli www.Chsciencedesign.com

Coni Stacher Hoerndli www.Chsciencedesign.com

Using GFP tagged GLR-1 receptors (C.elegans homologues of GluR1), we have previously established a microscopy platform enabling us to directly follow receptor transport in an intact nervous system in C.elegans. This approach revealed that Glr-1 receptors were very mobile, transported out from the neuronal soma and between synapses in vesicles moved by the molecular motor Kinesin-1. (Hoerndli et al., 2013). Furthermore, this transport was actively regulated by neuronal activity through calcium and calcium calmodulin-dependent kinase II (CaMKII). Indeed, we showed that presynaptic neuronal inhibition led to decrease somatic export of GLR-1 vesicles which could be bypassed by constitutively active forms of CaMKII (Hoerndli et al., 2015). Finally, chromophore-assisted-light-inactivation (CALI) of CaMKII in the cell body or specific synapses revealed that CaMKII was required for Kinesin-1 dependent mobility of GLR-1 vesicles essential for synaptic function and maintnenance.

At CSU the Hoerndli Lab is now investigating how CaMKII and related molecular signaling pathways control synaptic delivery and removal of GLR-1. In particular, we are interested in the role of ROS signaling downstream of calcium entry and phosphatases downstream of CaMKII signaling events that could modulate synaptic GLR-1 transport and function.

DOES ROS SIGNALING MODULATE SYNAPTIC GLR-1 TRANSPORT AND INSERTION?

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Rachel Doser a graduate student in the Hoerndli Lab has shown that both H202 treatment and a catalase loss of function mutant alters GLR-1::GFP transport. These preliminary results suggest that ROS levels can modulate GLR-1 transport dynamics. Using a genetic strategy, in vivo calcium and ROS sensors Rachel Doser is investigating the conditions in which ROS and Calcium signaling interact to modulate GLR-1 synaptic transport and insertion.


HOW DOES LAR-RPTP/PTP-3 REGULATE SYNAPTIC DELIVERY AND REMOVAL OF GLR-1?

How does aging change transport and synaptic function dependent on AMPARs ?

Coni Stacher Hoerndli www.Chsciencedesign.com

Coni Stacher Hoerndli www.Chsciencedesign.com

A large body of research has documented the decline of cognitive function during aging. Behavioral, structural and electrophysiological studies show that this includes, loss of synapses, neurons but more importantly also changes in synaptic plasticity. Therefore, it is not purely loss of synaptic transmission that occurs with time but also a gradual change in neuronal and synaptic function. Although, different from complex nervous circuits of the mammalian brain, neurons and their molecular communication rules in C.elegans are highly conserved. In addition, C.elegans ages rapidly showing signs of behavioral and neuronal degradation within 5-10 days old adult animals. This has made C.elegans one of the key genetic models to study the molecular pathways regulating cellular and neuronal aging.

Taking advantage of its transparency and genetic tractability the Hoerndli lab, is studying how long-distance ionotropic Glutamate Receptor transport is modified with age and which genetic signaling cascades contribute to these changes.


Light Induce Prion Aggregation in C.elegans In Vivo

Coni Stacher Hoerndli www.Chsciencedesign.com

Coni Stacher Hoerndli www.Chsciencedesign.com