Semblance Hypothesis

Additional Findings

A. In physiological conditions

1. Regenerative spikes at the dendritic arbour - a mechanism for internal sense of a place that reflects binding at the time of learning

Each place field consists of a unique set of CA1 neurons that fire action potential. At the dendritic regions, calcium transients informs about a change in potentials occurring regeneratively either due to back propagating action potentials (bAP) or by dendritic spikes. Recent studies observed calcium transients secondary to regenerative dendritic events in place cells that can predict place field properties (Sheffield and Dombeck, 2015a; Sheffield et al., 2017). These calcium transients have a highly spatiotemporally variable prevalence throughout the dendritic arbour. In some cases only a subset of the observed branches displayed detectable spikes, which indicates that spikes originated at these dendritic branches. None of the observed branches in many cases displayed detectable spikes during place field traversals while the soma (and axon) fired. This means that the bAP did not reach these locations.

An explanation is possible by the explaining that dendritic spike occurs at an islet of inter-LINKed spines that belong to different neurons that belong to different CA1 neurons (Vadakkan, 2013). This has the following advantages. a) Activation of inter-LINKed spines within an islet of inter-LINKed spines induces units of internal sensations for a specific place. b) One dendritic spike at an islet of inter-LINKed spines that belong to different neurons can explain firing of different CA1 neurons that are being maintained at a sub-threshold state at the time of the dendritic spike. It also supports why a high percentage of place cells are shared between different places. c) Since potentials degrade as they reach the axonal hillock, it may require more than one spike to contribute to the firing of a CA1 neuron depending on latter’s sub-threshold level. d) Highly spatiotemporally variable nature of spike depends on the qualia of internal sensations that they induce in response to and matching with the place (which depends on previous associative learning events with different places). The latter property can explain the expected binding feature (Sheffield and Dombeck, 2015b).

Sheffield MEJ, Dombeck DA (2015a) Calcium transient prevalence across the dendritic arbour predicts place field properties. Nature. 517(7533):200-204. PubMed

Sheffield MEJ, Adoff MD, Dombeck DA (2017) Increased Prevalence of Calcium Transients across the Dendritic Arbor during Place Field Formation. Neuron. 96(2):490-504.e5 PubMed

Vadakkan KI (2013) A supplementary circuit rule-set for neuronal wiring. Frontiers in Human Neuroscience. 7:170 PubMed

Sheffield ME, Dombeck DA (2015b) The binding solution? Nature Neuroscience. 18(8):1060-102 PubMed


B. In pathological conditions

  1. Spread of epileptic activity

Epileptic activity in the hippocampus propagates with or without synaptic transmission at a speed of nearly 0.1m/s (Jefferys, 2014). Experiments showed longitudinal propagation of epileptic activity from one end of a neuronal order to its other end in the hippocampus takes place independent of chemical or electrical synaptic transmission (Zhang et al., 2014). Since this spread of epileptic activity occurs at a speed of 0.1 m/s and is not compatible with ionic diffusion or pure axonal conduction (Jefferys 2014; Zhang et al., 2014), it requires an explanation at the cellular and electrophysiological levels. In this regard, rapid chain propagation through the inter-postsynaptic functional LINKs (IPLs) explained by the semblance hypothesis (Vadakkan, 2015) offers a suitable explanation for a mechanism.

Jefferys JG (2014) How does epileptic activity spread? Epilepsy Currents. 14(5):289-290 PubMed

Zhang M, Ladas TP, Qiu C, Shivacharan RS, Gonzalez-Reyes LE, Durand DM (2014) Propagation of epileptiform activity can be independent of synaptic transmission, gap junctions, or diffusion and is consistent with electrical field transmission. Journal of Neuroscience. 2014 34(4):1409-1419 PubMed

Vadakkan KI (2016) Rapid chain generation of interpostsynaptic functional LINKs can trigger seizure generation: Evidence for potential interconnections from pathology to behavior. Epilepsy & Behavior. 59:28-41 PubMed