The provided code is part of a computational neuroscience model focused on understanding synaptic signaling mechanisms, particularly those related to AMPA receptor dynamics in the post-synaptic neuron. Here, the code is modeling how changes in AMPA receptor subunit composition and dimerization affect synaptic conductance in the context of neuronal excitability. ### Key Biological Aspects: 1. **AMPA Receptor Subunits:** - The model considers two AMPA receptor subunits, GluR1 and GluR2, which are crucial for synaptic transmission. These subunits form tetramers that constitute functional AMPA receptors. The code explores scenarios where either GluR1 or GluR2 is absent or present in specific proportions, which can affect synaptic plasticity and receptor functionality. 2. **Tetramer Formation Rules:** - The model examines two tetramer formation rules: the normal rule and an alternative "dimer-of-like-dimers" rule. These formation rules impact the receptor's conductance properties. The "dimer-of-like-dimers" formation posits that each dimer is composed of like subunits, potentially affecting receptor behavior under various synaptic conditions. 3. **Synaptic Plasticity Protocols:** - The code simulates synaptic conductance under high-frequency stimulation (HFS) and low-frequency stimulation (LFS) protocols. These protocols mimic physiological stimuli that drive synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). 4. **Intracellular Signaling Pathways:** - The model includes several signaling pathways: - **CaMKII Pathway:** Involves calcium (Ca) and proteins like CaMCa4 and CaMKII, implicated in synaptic plasticity. - **Gs/Gi-cAMP-PKA Pathway:** Encompasses signaling via G protein-coupled receptors (like β-adrenergic receptors), modulating cyclic AMP (cAMP) and protein kinase A (PKA) activity. - **Gq-PLC-PKC Pathway:** Involves phospholipase C (PLC) and protein kinase C (PKC) signaling, influenced by neurotransmitter release and receptor activity. 5. **Phosphorylation Sites:** - Multiple phosphorylation sites on GluR1 and GluR2 are considered, which affect receptor trafficking and synaptic insertion. Notable sites include S831 and S845 on GluR1 and S880 on GluR2. Phosphorylation of these serines can modulate receptor function and synaptic strength. 6. **Receptor Surface Expression:** - The code tracks the dynamic expression of AMPA receptor subunits at the membrane level, which is critical for changes in synaptic strength during neural signaling events. 7. **Fluorescent Indicators:** - The code uses fluorescence indicators (e.g., Gluflux) to model ligand concentrations like glutamate and acetylcholine, which are essential for neurotransmission and receptor activation. This model provides insights into how alterations in AMPA receptor subunit composition and phosphorylation states can influence synaptic conductance, thereby contributing to our understanding of synaptic plasticity and its role in learning and memory processes.