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Growth and development of the postsynaptic active region of an excitatory glutemergic synapse: An integrated model

Venkateswaran Nagarajan1*, Vishal Raghu2, Ganesh Ranganath Chandrasekar2 and Kapardi Mallampalli2
  • 1 Waran Research Foundation, India
  • 2 Waran Research Foundation, India

In an excitatory dendrite, the genesis of a synapse begins with a dendritic filopodium making a tactile contact with a presynaptic bouton due to growth initiated by BDNF-TrkB mediated actin polymerisation in the filopodium. During its development, the postsynaptic spine head enlarges and the apical periphery becomes the site for synaptic activity. The assimilation of the postsynaptic density (PSD) in this site marks the begining of postsynaptic development, which subsequently develops to become the kernel of synaptic activity and provides a scaffolding that houses the receptors, CAMs and the various growth related protiens, the study of which is incipient. The morphology of PSD and the potentiation of an excitatory synapse have a relationship that is synergic in nature.  Our petrinet based model aims to trace the genesis and the morphological modifications undergone by the PSD of the postsynaptic region of an excitatory glutemergic synapse, begining from the genesis of an excitatory synapse, through the various stages of its development. The chief signalling pathways include those triggered by NMDA and AMPA receptors, Trkb-BDNF, Integrin and Epherin and the ionotropic receptors that are the focus of our study are NMDA and AMPA where NMDA acts as a ligand gated ion channel for Ca2+ and AMPA for Na+. In our model, we have proposed a mechanism that controls the shape of the postsynaptic region of synaptic activity as a function of the positions of neuriligin (Nlg-1) molecules on the PSD platforms through a method of zonal actin polymerization (ZAP). Acoording to our hypothesis, the polymerization of actin occurs in individual "zones" beneath the PSD. The zones which underlie the Nlg-1 pillars or, are in their vicinity, have inhibitted growth due to excess opposing force offered by the PSD, in comparision with zones devoid of Nlg-1 influence. Depending upon the positions of the Nlg-1 molecules near the centre and/or at the ends of the PSD, a plethora of shapes starting from a convex spherical spine head to a concave cup-shaped one can be obtained. Furthermore, we intend to incorporate a system of retrograde signalling mediated the generation and release of retrograde messangers which is instigated by Ca2+ influx in the postsynapse. The activation of the PLC pathway by neurotrophins produces DAG from the lipids upon hydrolysis. DAG then generates the endocannabinoid receptor messengers upon interaction with Ca2+.

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Keywords: AMPA receptor trafficking, PSD-95, Bdnf-trkB signaling, Morphogenesis, actin polymerization, neurotransmitters

Conference: Neuroinformatics 2014, Leiden, Netherlands, 25 Aug - 27 Aug, 2014.

Presentation Type: Poster, not to be considered for oral presentation

Topic: Computational neuroscience

Citation: Nagarajan V, Raghu V, Chandrasekar G and Mallampalli K (2014). Growth and development of the postsynaptic active region of an excitatory glutemergic synapse: An integrated model. Front. Neuroinform. Conference Abstract: Neuroinformatics 2014. doi: 10.3389/conf.fninf.2014.18.00056

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Received: 22 Apr 2014; Published Online: 04 Jun 2014.

* Correspondence: Prof. Venkateswaran Nagarajan, Waran Research Foundation, Chennai, Tamil Nadu, 600033, India, waran@warftindia.org