Ephaptic conduction molding memory engrams

Abstract

Background: Memories are programmed in the brain as connected neuronal ensembles called engrams. However, the method by which the brain forms engrams during memory encoding is not understood.

Results: We have created a mechanistic mathematical model showing a possible method of the encoding process. Our model is based on the cellular automata approach, which can specifically distinguish between neurons operated on by the synaptic and those operated on by the ephaptic modes. This feature allows us to confirm that the ephaptic mode induces the formation of repeating collections of operating neurons (sub-engrams) that can become memory-preserving entities, and the synaptic influence is manifested by molding these sub-engrams by pruning small ones and size-increasing and rounding larger ones to form the engrams' final structures.

Conclusions: Ephaptic and synaptic dual-participation in the memory encoding process was exhibited. The sequence of activities was unveiled. We also speculate on possible procedures the brain can employ to enable the ephaptic mode to overtake the normal, synaptic-dominating one.

Keywords: Engram formation; Ephaptic domination; Memory encoding; Sub-engrams; Synaptic molding.

Fig. 1

Block diagram of the model. Schematic presentation of a cell (neuron) transformation from waiting to operation and backwards under synaptic and ephaptic conductions. Shown are the waiting, delayed (for the ephaptic case), refractory, and active neural modes

Fig. 2

The transition from synaptic domination to ephaptic domination of information transport in the brain is controlled by the competence of neurons to accept ephaptic cues, CNEC (b) parameter. This domination is depicted by the final average numbers of both ephaptic and synaptic-induced operating cells in a run of 10 matrices initiated by 100 randomly chosen operating cells, as a function of b. The influence of the synaptic conduction is represented by its enabling parameter, p, shown in its normal (non-epileptic) range, between 65 and 90%

Fig. 3

The quick transfer to an ephaptic mode domination under a jump of the b parameter. Time dependence of ephaptic domination following an abrupt b-change from 2.5 to 2.3. For 1TU ~ 1 ms, the transition lasts less than 100 ms

Fig. 4

Sub-engram locations in a tissue driven by purely ephaptic conduction. A tissue (matrix) of 40 × 40 cells was initiated, a by activating 200 randomly chosen cells. The “ephaptic delay” (see the model section) duration is 4 TUs. b–e show the ensuing sub-engrams. They depict active patches of repeating operating cells (sub-engrams) 4 TUs apart, following 800 TUs from the initiation. The oscillation duration is 8 TU, repeating after two 4TU steps. Such 2-step oscillations are called “blinkers” in cellular automata nomenclature (Oscillator (cellular automaton), Wikipedia)

Fig. 5

Synaptic molding of sub-engrams (40 × 40 matrix; 200 initially operating cells; b = 2; p = 30%): (1) pruning of a small sub-engram. A repeating sub-engram of 4 cells and its “engulfment” by a synaptic influence. Cells activated by the ephaptic mode are in blue, while those activated by the synaptic mode are red. The matrix parts showing the structure are depicted every 4 TUs. The cycle of 2 (of 8 TU’s duration) is illustrated by the blue cells in 4a, b, c. The synaptic influence at 4c leads to the shape change at 4d and a subsequent object elimination

Fig. 6

Synaptic molding of sub-engrams (40 × 40 matrix; 200 initially operating cells; b = 2; p = 30%): (2) shaping, synaptic operation is observed by the increasing number of ephaptic-initiated operating cells (Nef) from 39 in 5a to 55 in 5 h and by the change of engram shape

Fig. 7

Engram location in a tissue operated on by ephaptic and (diminished) synaptic conductions (b = 2). Initial conditions are similar to those of Fig. 4, with 100 initially operating cells. Shown are matrices, 4 TUs apart, following 800 TUs from the start. Only a single pattern remained in this matrix