The spatiotemporal spread of biochemical signals in neurons and other cells regulate signaling specificity, tuning of signal propagation, along with specificity and clustering of adaptive plasticity. Theoretical and experimental studies have demonstrated a critical role for cellular morphology and the topology of signaling networks in regulating this spread. In this study, we add a significantly complex dimension to this narrative by demonstrating that voltage-gated ion channels (A-type Potassium channels and T-type Calcium channels) on the plasma membrane could actively amplify or suppress the strength and spread of downstream signaling components. We employed a multiscale, multicompartmental, morphologically realistic, conductance-based model that accounted for the biophysics of electrical signaling and the biochemistry of calcium handling and downstream enzymatic signaling in a hippocampal pyramidal neuron. We chose the calcium – calmodulin – calcium/calmodulin-dependent protein kinase II (CaMKII) – protein phosphatase 1 (PP1) signaling pathway owing to its critical importance to several forms of neuronal plasticity, and employed physiologically relevant theta-burst stimulation (TBS) or theta-burst pairing (TBP) protocol to initiate a calcium microdomain through NMDAR activation at a synapse.
Model Type: Dendrite; Synapse; Channel/Receptor; Neuron or other electrically excitable cell
Region(s) or Organism(s): Hippocampus
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Currents: Ca pump; I A; I_SERCA; I Calcium; I_K,Na; I h; I Potassium
Model Concept(s): Active Dendrites; Detailed Neuronal Models; Calcium dynamics; Reaction-diffusion; Signaling pathways; Synaptic Plasticity
Simulation Environment: NEURON
Implementer(s): Basak, Reshma [reshmab at iisc.ac.in]; Narayanan, Rishikesh [rishi at iisc.ac.in]
References:
Basak R, Narayanan R. (2018). Active dendrites regulate the spatiotemporal spread of signaling microdomains. PLoS computational biology. 14 [PubMed]