Semblance Hypothesis

Testable Brain Activity Map

(Map of the route from the Brain to the Mind)

Brain activity involves receiving sensory information, causing conscious interpretation of some of them, resulting in behavioral motor activities based on previous associative learning, and storing some of the newly received information. What type of a brain activity map can provide these functions? We have been attempting to understand the nervous system using the anatomical connections of the 302 neurons of the worm C. elegans during the last twenty five years. Why didn’t we succeed in understanding the nervous system? What are we missing here? The nervous systems of animals are more complex that we will be required to obtain explanations for more functions. Exhibition of more functions using similar basic units is likely to provide more pieces of the puzzle that may aid in understanding it.

One of the essential features of the brain function is the formation of inner sensations of higher brain functions (e.g. memory, consciousness) as a first-person property. Studying this property requires a completely new approach separate from current anatomical, molecular biological and electro-physiological approaches; but at the same time adhering to their basic principles. In order to understand what approaches need to be taken it is required to build a hypothesis that can explain various brain functions. Since most of the higher brain functions are internal sensations within the mind that are formed as first-person perspectives, then the working hypothesis should have bridges from cellular and electro-physiological properties to those virtual internal sensations.

Once a hypothesis is built, it requires to be tested by three essential steps. First, test whether the hypothesis can explain what we have already discovered in various faculties of brain sciences. Luckily, the nervous system is complex enough that we can ask many questions to verify the validity of the hypothesis. Secondly, are there any new structures or functions proposed in the hypothesis? If they are testable, the next will require testing them. Once these are carried out, we will be in a good position to move forward. Semblance hypothesis has provided satisfactory evidence from previously published work from different laboratories. Thirdly, how to address the issue of the first-person properties of brain functions? We need to carry out the gold standard test of replicating the mechanism in engineered systems to finally confirm the findings. This is required since the higher brain functions of the mind that are first-person properties require this step to convert the first-person perspectives to appropriate read-outs so that we experimenters (second persons) can understand them. This will not only test the hypothesis, but also pave the way for developing artificial intelligence.

Semblance hypothesis was proposed towards achieving these goals. It has provided sufficient explanations for various electro-physiological, behavioral and systems findings from different faculties of brain sciences. The essential feature of the hypothesis is the proposal of inter-postsynaptic functional LINK. An examination of the possible nature of this was then carried out. From examining disease processes that can alter the inter-postsynaptic functional LINKs, it was possible to arrive at a reasonable conclusion that inter-postsynaptic membrane hemi-fusion is a candidate mechanism. This can be tested in animals and human samples. Its formation and functional role can be tested both during associative learning, and during the induction of long-term potentiation (LTP), one of the experimental correlates of behavioral motor activities expected of the animals during memory retrieval. Brain activity map, based on semblance hypothesis, is explained by the following two figures (Figures 1, 2).

                                          Brain Activity Map                               

Figure 1: Comparison between the known synaptically-connected circuitry (left side) and the inter-postsynaptic functional LINK-mediated wiring (right side).

Left panel: Synaptically connected conventional neuronal circuit diagram. There is one synaptic connection between neurons N1 and N2. The activation of neuron N1 induces an excitatory postsynaptic potential (EPSP) at postsynaptic membrane B. Provided neuron N2 is simultaneously receiving EPSPs from other neurons, the sum of which is just one EPSP short for spatial summation to trigger an action potential, then the EPSP arriving at postsynapse B from the activation of neuron N1 will lead to the firing of neuron N2. The contribution of the EPSP from the activation of Neuron N1 toward the temporal summation of EPSPs to elicit an action potential in neuron N2 should also be considered. Otherwise, a single EPSP or a train of few EPSPs reaching at postsynapse B alone may not induce an action potential of neuron N2.

Right panel: Wiring diagram based on the present work. The activation of neuron N1 activates the inter-postsynaptic functional LINKs between the postsynapses in the islet of functional LINKs (see "Frequently asked questions" page in this website). The re-activation of postsynapse B that belongs to neuron N2 can provide EPSP and enable neuron N2 to fire an action potential similar to the threshold conditions explained for neuron N2 of the conventional wiring diagram (in the left panel figure). In addition, EPSPs spread to other hemi-fused postsynapses D, F, H, J, and L (depending on the extent of the spread through the islet) that can reach toward their neuronal somata. According to the supplementary rules, a total of six postsynapses are re-activated here, in comparison to only one by the canonical synaptic transmission (Figure in the left panel). This increases the probability for firing of sub-threshold activated neurons in the next order by bringing them toward the threshold for activation. For example, neuron N6 continuously receives (n − 1) EPSPs, just short of one EPSP toward either spatial or temporal summation to elicit an action potential. Arrival of the nth EPSP from the islet of functionally LINKed postsynapses enables neuron N6 to cross the threshold to elicit an action potential (shown in red). If neuron N6 is a motor neuron, it can evoke motor activity concurrent with the re-activation of the functionally LINKed postsynapses B, D, F, H, J, and L. Activity through these LINKed postsynapses will also evoke semblions for the formation of internal sensations provided these are located at regions of oscillatory neuronal activity. All the neurons in red receive sufficient summated EPSPs and fire action potentials. Note that the lateral spread of activity through the inter-postsynaptic functional LINKs provides the horizontal vector for the oscillatory neuronal activities observed both in the cortex and hippocampus. It is marked by a red wave passing through the islet of inter-postsynaptic functional LINKs. Even though ideally it should be drawn over the firing neurons, drawing it over the functional LINKs makes its operation more functionally directed (Modified from Vadakkan K.I. (2013) A supplementary circuit rule-set for neuronal wiring. Frontiers in Human Neuroscience).


Figure 2. Diagram showing the formation of internal sensations and fine control of the motor activation by a cue stimulus. Oscillating neuronal activity results in the activation of many downstream neurons. They can be kept tonically inhibited under resting conditions (not shown) to subthreshold levels such that they can be disinhibited at the arrival of one or a few excitatory postsynaptic potentials (EPSPs). There were two associative learning events that occurred previously with the cue stimuli. The first one was with items 1 and 2. After this first step of associative learning, the cue stimulus was retrieving memories of items 1 and 2. Note the reactivation of a sparse inter-postsynaptic functional LINK in the cortex. Along with retrieving memory of the second item, cue stimulus also evokes a motor response using the motor neuron. At a later time, the same cue stimulus had undergone a second associative learning event with item 3. Following this second learning event, the cue stimulus evoked internal sensations (semblances) of learned items 1, 2 and 3. However, as the semblance for item 3 was evoked, it also resulted in an inhibition of the motor activity (note the output from postsynapse D3 providing inhibitory potentials to the upper motor neuron). This type of an event is an example of the behavioral inhibition occurring at the frontal cortices. Complexities of the internal sensations can be based on the nature of the cue stimulus, previous associative learning, and the type of the nervous system. Reward-induced associative learning may be facilitated by dopamine-induced enlargement of dendritic spines (Yagishita et al., 2014) that promotes possible inter-postsynaptic membrane hemifusion and its stabilization for a long period of time. Also note that the cue stimulus reactivates inter-postsynaptic functioanl LINKs at other cortical areas to evoke memories for learned item 1. Since the inter-postsynaptic functional LINKs are transient and need reinforcement for long-term persistence, the induction of a minimum number of inter-postsynaptic functional LINKs alone may not maintain the effect of learning for a long period of time. In the hippocampus, the reactivation of inter-postsynaptic functional LINKs in response to spatial stimuli is expected to induce semblances for memories associated with that space and the EPSPs arriving through the inter-postsynaptic LINK induce firing of subthreshold-activated CA1 neurons (place cells). This explains how spatial memories are associated with place cell firing. Formation of circuits in this manner can explain the induction of internal sensations along with simultaneous behavioral motor action. Three sensory cortices are marked to indicate that the sensory stimuli can be of different types. EPSP: excitatory postsynaptic potential. (n)th EPSP: the last EPSP necessary to achieve threshold EPSP to generate an action potential. Each motor action will evoke certain sensory stimulus in the form of proprioception that will act as a feedback stimulus to the system confirming that the motor action was executed. N: Excitatory neuron; IN: Inhibitory neuron. A and C: Presynaptic terminals; B and D: Postsynaptic terminals. Red line between B and D: Inter-postsynaptic LINK. (+) stimulation; (-) inhibition (Modified from Vadakkan KI, Reviews in the Neurosciences, 2015).

The brain activity map that is built of the basic units presented here can an explain large number of nervous system functions (Table 1) that are observed by different faculties of brain sciences.

        Operates in unison with synaptically-connected neurons

     Testable mechanism that can induce virtual internal sensations

     Retrieval of memory takes place at physiological time-scales

     Specificity for retrieved memory in response to a specific cue stimulus

     Explains working, short and long-term memory as part of the same mechanism

     Has provision for forgetting

     Dependent on the extracellularly recorded oscillating potentials

     Explains motivation-induced increase in learning due to dopamine’s effect

     Has the ability to store very large number of memories

     Can explain how memory can be retrieved after very long period of time after the learning

     Explains how locations of memory storage can be changed to explain consolidation of memory

     Explains a framework for the system to make a hypothesis

     Provides mechanism for internal sensation of sensory perception

     Explain how place cell fire in the presence of a spatial stimulus

     Ability to initiate motor activity with only an intention to move

     Explains innate behavior for survival of the animal. For example, for sucking, swallowing

     Loss of function explains pathologies

      a)  Dementia occurring secondary to various aetiologies

      b)  Neurodegeneration

      c)  Hallucinations in psychiatric disorders

     Explains how dopamine can induce hallucinations

     Explains a cellular mechanism for long-term potentiation (LTP)

     Explains how the system operates with very low energy expenditure

     Provided a framework for consciousness

     Provided an explanation how consciousness is correlated with oscillating potentials

     Provided a feasible mechanism of action of anesthetic agents that blocks consciousness

     Explains how dopamine that can enlarge dendritic spines reduce requirement for anesthetics

     Inter-postsynaptic functional LINKs match with K-lines proposed (Minsky, 1979)

     Testable both in biological and engineered systems

Table 1. List of various brain functions, some of them at least as frameworks, which can be explained by semblance hypothesis.

The basic cellular operational principle for the first person internal sensations of all the higher brain function should be sharing a common cellular mechanism. This will allow the common feature of induction of internal sensations in these higher brain functions. Inter-postsynaptic functional LINKs and the induction of semblance is capable of providing adequate mechanistic cellular features. Since the expected solution that can explain wide range of findings at several levels is expected to be a unique one, the proposals made by semblance hypothesis can be considered for verification by testing the predictions made by the hypothesis and replicating the mechanism in engineered systems.