Abstract
Limitations of known anatomical circuit rules necessitate the identification of supplementary rules. This is essential for explaining how associative sensory stimuli induce nervous system changes that generate internal sensations of memory, concurrent with triggering specific motor activities in response to specific cue stimuli. A candidate mechanism is rapidly reversible, yet stabilizable membrane hemi-fusion formed between the closely apposed postsynaptic membranes of different neurons at locations of convergence of sensory inputs during associative learning. The lateral entry of activity from the cue stimulus-activated postsynapse re-activates the opposite postsynapse through the hemi-fused area and induces the basic units of internal sensation (namely, semblions) as a systems property. Working, short-term and long-term memories can be viewed as functions of the number of re-activatible hemi-fusions present at the time of memory retrieval. Blocking membrane hemi-fusion either by the insertion of the herpes simplex virus (HSV) glycoproteins or by the deposition of insoluble intermediates of amyloid protein in the inter-postsynaptic extracellular matrix (ECM) space leads to cognitive impairments, supporting this mechanism. The introduction of membrane fusion blockers into the postsynaptic cell cytoplasm that attenuates long-term potentiation (LTP), a correlate of behavioral motor activities in response to memory retrieval, provides further support. The lateral spread of activity through the inter-postsynaptic membrane is capable of contributing to oscillating neuronal activity at certain neuronal orders. At the resting state these oscillations provide sub-threshold activation to many neurons at higher orders, including motor neurons maintaining them at a low initiation threshold for motor activity.
Highlights
If non-specific inter-postsynaptic functional LINKs occur at certain neuronal orders, they are expected to cause cognitive deficits via the formation of non-specific semblions, the activation of a new set of neurons, hallucinations resulting from semblances connecting features of different previously associatively learned items and changes in oscillatory neuronal activities resulting in changes in consciousness
This can be explained by the requirement for cue-induced synaptic activation that will re-activate the functional LINK that induces both the formation of the internal sensation of memory and provides the additional Excitatory postsynaptic potential (EPSP) required for the activation of sub-thresholdactivated neurons
The inter-postsynaptic functional LINKs can provide these requirements, which include the retrieval of memories at physiological time-scales, the consolidation of memories (Vadakkan, 2011a); the ability to support a framework of consciousness (Vadakkan, 2010a), the ease of learning related items; working memory resulting from semblances from all the functional LINKs immediately after learning; deterioration of the strength of memories immediately following learning as the hemi-fused membranes reverse back to their low-energy state independent membranes; the repetition of learning maintaining the hemi-fusions for long periods of time until certain transmembrane proteins are inserted across them enabling long-term memories; the role of new neurons in losing, improving, and expanding the locations of formation of memories; and the sharing of the mechanism of inter-postsynaptic membrane hemifusion in memory with long-term potentiation (LTP)
Summary
Limitations of known anatomical circuit rules necessitate the identification of supplementary rules. This is essential for explaining how associative sensory stimuli induce nervous system changes that generate internal sensations of memory, concurrent with triggering specific motor activities in response to specific cue stimuli. Blocking membrane hemi-fusion either by the insertion of the herpes simplex virus (HSV) glycoproteins or by the deposition of insoluble intermediates of amyloid protein in the inter-postsynaptic extracellular matrix (ECM) space leads to cognitive impairments, supporting this mechanism. The introduction of membrane fusion blockers into the postsynaptic cell cytoplasm that attenuates long-term potentiation (LTP), a correlate of behavioral motor activities in response to memory retrieval, provides further support. The lateral spread of activity through the inter-postsynaptic membrane is capable of contributing to oscillating neuronal activity at certain neuronal orders.
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