Recent research into whole genome mapping of the mouse brain has made possible direct investigation of the brain expression of unusual genes. A search of the Allen Brain Atlas database has provided genetic and neuro-anatomical evidence for widespread specific expression in the brain of eight genes specific to sensory transduction, in vision, hearing and touch. A novel biophysical model is proposed for the function of these proteins, in generating the internal model of experiential reality

Chris C. King

English

Nature Precedings

New Light on the Sensory Brain  1 
Sensory Transduction and Subjective Experience 
Expression of eight genes in three senses suggests a radical model of consciousness 
Chris King, Mathematics Department, University of Auckland  
21st June 2007 
 
Abstract:  Recent research into whole genome mapping of the mouse brain has made possible direct 
investigation of the brain expression of unusual genes. A search of the Allen Brain Atlas database has 
provided genetic and neuro-anatomical evidence for widespread specific expression in the brain of 
eight genes specific to sensory transduction, in vision, hearing and touch. A novel biophysical model is 
proposed for the function of these proteins, in generating the internal model of experiential reality. 
 
Introduction 
Recent research in whole genome mapping of the mouse brain 1,2 
has made it possible to investigate the potential central nervous 
function of genes that might otherwise be associated primarily 
with peripheral sensory transduction. At the same time, the actual 
molecules involved in sense transduction, in vision, hearing and 
touch are being characterized.  The first putative transduction 
molecule for mammalian touch, stomatin-like protein 3  (SLP3, or 
Stoml3) was reported this year in Nature 3, and putative 
molecules in the auditory transduction pathway, epsin 4,5, and 
cadherin 23 (otocadherin) 5 have only been reported in the last 
five years and otoferlin 6,7 in 2006.  Research into the genetic 
evolution of the visual system has also unearthed provocative 
new findings about vision, which became the trigger for this 
hypothesis.  In parallel with the usual cilia-based photo-
transducer molecule c-opsin are retinal ganglion cells, which use 
melanopsin, or r-opsin related to insect opsins (based on 
organelles called rhabdomeres), which depolarize rather than 
hyperpolarize 8.  It has also been discovered that both types of 
opsin work in opposition in the reptile parietal (pineal) eye 9. 
 
Figure 1: Large scale mouse brain expression profiles of encephalopsin 
(Opn3), otocadherin (Cdh23), espin (Espnl), otoferlin (Otof) and Stom3 
(Allen Brain Atlas1) illustrate the wide and discretely specific expression 
of sensory transduction molecules for three senses, vision, hearing and 
touch in the central nervous system.  Does this mean that the !internal 
model of reality" evokes subjective experience using similar molecules to 
the physical senses?  
 
Investigation 
Interest in such idiosyncratic incidences of sensory genes 
became the stimulus for making a short investigation of 
molecules associated with sensory transduction in brain tissues, 
using the Allen Brain Atlas 1 of the mouse. This immediately 
threw up a further opsin variant, encephalopsin 10, discovered in 
1999 and known to have a broad and selective distribution in the 
brain, including, but not restricted to, areas involved in visual 
processing. At the same time as making this search, Nature 
reported the discovery of Stoml3 in touch transduction 3 and a 
search revealed this also has a wide brain distribution. Stoml3 
was found to bind specifically to acid-sensitive ion channels 
ASIC2 and 3 and a search likewise found a CNS-wide expression 
of these genes. Finally a search was made for auditory 
molecules, which threw up epsin and cadherin-23 4,5, which 
likewise show brain-wide specific expression. Subsequently, the 
recent characterization of otoferlin 6,7, claimed to be key to the 
sensitivity of auditory transduction led to exploration of this 
auditory molecule as well, providing evidence of wide-spread 
expression from five genes involving three senses.  
New Light on the Sensory Brain  2 
 
Figure 2: Exploded view in the lateral ventral cortex at the cellular 
level of expression of encephalopsin (Opn3), otocadherin (Cdh23), 
espin (Espnl), otoferlin (Otof) and Stom3 demonstrate specific 
expression of a similar type in cortical tissue at the cellular level. 
 
In support of the central nervous expression of genes 
believed to be associated primarily with sensory transduction, 
an exploration of: (a)  rhodopsin, and encephalopsin, (b) 
otocadherin, espin, and otoferlin and (c) acid-sensitive ion 
channels ASIC2 and 3 and stomatin-like protein 3  using the 
Allen Brain Atlas is included in the figures.  Figure 1 shows 
lateral sagittal views of the whole mouse brain for five of 
these genes, supporting  their expression in the brain.  Figure 
2 Figure 2 looks in detail at an area of the ventral lateral 
cortex illustrating similar expression of each of these genes at 
the cellular level.  Figure 3 shows the specific expression of 
rhodopsin in the cortex focused in areas consistent with visual 
function. Figure 4 exemplifies more specialized activity of two 
of them in the olfactory bulbs and cerebellum. Figure 5 shows 
varying expression for four of the genes in the parietal cortex. 
 
Could the CNS contain Transduction Cascades? 
 
Opsins are clearly transducers from photonic to 
electrochemical. Encephalopsin is also expressed in other 
organs, and is also referred to as panopsin, so could have 
another generalized cellular function. However there are 
several other opsins of interest expressed in the CNS. 
Pinopsin is not confined to the pineal but also occurs widely in 
the brain. In addition vertebrate ancient opsin is also 
expressed in regions bordering the pineal. Rhodopsin has 
activity concentrated in individual neurons across the cortex 
with a specific focus in the occipital, consistent with a function 
in the primary visual cortex. 
 
Otoferlin, which was only characterized in Oct 2006, is as close as research can establish to the 
transduction step. Otoferlin functions right in the critical steps of the signaling cascade stimulating the 
fast kinetics of the most mature Ca dependent neurotransmitter vesicles, thus triggering the receptor 
cell response, and it's also transmembrane and possibly a Ca channel so it is right on the transduction 
interface.  In particular Parsons 6 notes that the hair cell has evolved a unique calcium-sensing 
molecule, otoferlin, for controlling neurotransmitter release. The action of otoferlin allows a hair cell"s 
specialized synapses — ribbon synapses, a specific class of afferent synapse common to sensory 
systems — to meet the requirements of hearing. Roux et. al. 7 describes otoferlin as a novel protein 
and transmembrane cochlear-expressed gene. So its function looks like a Ca++ ion channel or channel 
modulator that excites mature kinetically unstable vesicles. This could be the direct result of a 
phononic or solitonic event in the membrane. 
 
The presence of no less than three molecules from the auditory transduction pathway - otoferlin, 
otocadherin and espin in the CNS suggests functional linkage in the CNS and a possible signaling 
cascade. All three don't have to be directly involved in transduction, but all may be essential to it, as is 
evidenced by deafness studies.  
 
SLP3 is a transduction modulator, which binds specifically to acid-sensitive ion channels ASIC 2&3.  
The atlas found very similar cortical distributions of all three molecules, again setting up a putative 
model for a transduction cascade here as well.  However ASIC may have more general ion-channel 
functions in the CNS which makes the role of SLP3 interesting. Wetzal et. al. 3 show mechano-
sensitive ion channels found in many sensory neurons do not function without SLP3 including touch 
mechanoreceptors as a whole and cites their coupling to ASIC 2&3. 
  
New Light on the Sensory Brain  3 
 
Figure 3: Expression of rhodopsin in 
the CNS shows both strong selective 
neuronal expression and a focal 
expression in the occipital cortex 
consistent with expression in the 
primary visual areas. 
 
Subjective Consciousness and 
Biophysical Transduction 
 
Interest in the biophysical basis of 
subjective consciousness has 
become central to the emerging area 
of consciousness research.  A variety 
of models have been put forward for 
the involvement of CNS proteins in, 
quantum computation by orchestrated objective reduction in microtubules12,13,14, and others involving 
coherent quantum excitations including a  protein/water/EM field model15,16,17,18.   A variety of functional 
proteins in the CNS are under investigation to test for their possible role in the biophysical 
underpinning of subjective consciousness. It has also been proposed that conscious anticipation might 
be made possible through quantum excitations both emitted and absorbed by the CNS 27,28. 
 
Although subjective consciousness has many attributes, from the sense of self-awareness (self-
consciousness) through semantic and rational processes (rational mind) and working memory, some 
of which involve subliminal processing on the fringes of consciousness or unconsciously, there is a 
major central arena of conscious experience, sometimes referred to as the Cartesian theatre 19,20, 
which gives the subjective expression of an envelope of sensory experience, whether it involves 
experiences of the external world or purely internal states such as dreaming.  This in turn gives rise to 
the notorious binding problem – how a distributed parallel processing organ like the cortex with 
disparate sensory areas can bring in all back together.  However the primacy of internal !sensory 
experience" in subjective consciousness suggests a biophysical support based on the same principles 
as are involved in sensory transduction. 
 
Figure 4: Specialized expression of encephalopsin (Opn3) in the 
cerebellum, and of otocadherin (Cdh23) in the olfactory lobes illustrate 
divergent specialized function of these genes in specific brain areas 
contrasting with their similar expression in figure 2. 
 
The occurrence of putative sensory transduction genes in the 
central nervous system is consistent with a novel biophysical 
model supporting subjective consciousness – that the 
distributed functioning of the central nervous system provides 
an !internal sensory system" which can generate abstracted 
sensory experiences of reality forming an !internal model of 
reality" using the same physical principles as are involved in 
sensory transduction in a bi-directional manner, enabling 
coherent generation and reception of biophysical excitations, 
particularly those associated with vision and audition. Olfaction has a fundamentally different basis, 
both in brain architecture and in the fact that it involves specific molecular receptors, which cannot 
regenerate their stimuli by reverse transduction, although there is evidence for olfactory synesthesia 
21,22. Some forms of synesthesia, such as responding with feeling to seeing another person"s finger 
touched 23, may also involve specific interactive circuitry, including mirror neurons 24. 
 
The model gives a succinct explanation of why subjective experience such, as dream, memory and 
reflection, as Carl Jung 25 put it, so successfully evokes the deep qualitative differences between the 
senses, when a purely electrochemical model has no qualitative differences between the senses, 
except in terms of differential developmental and stimulus-induced processing connectivities. The wide 
distribution of each of these molecules, not confined to one sensory area, suggests that the evolution 
of the cortex as an adaptable system, has resulted in a flexible design, in which widespread areas of 
New Light on the Sensory Brain  4 
the brain may be capable of generating dynamics simulating more than one sensory process 
biophysically, consistent with descriptions of kaleidoscopic synesthesia 21 in the medical literature, in 
psychedelic folklore, and manifest in ancient cave art running far back into our human origins 26.  
 
By contrast with all other areas of scientific discovery, from the human genome to cosmological grand 
unification, the nature and basis of conscious experience remains the principal scientific area in the 
third millennium for which there is yet no realizable candidate theory, nor even a qualitative 
understanding in principle, of how our !internal model of reality" is generated. While consciousness 
research has come in from the cold as an accepted scientific research area 12,27, there are still major 
stumbling blocks to a realizable theory of consciousness, including the !hard problem" 30 – whether 
subjective consciousness is in any way qualitatively identifiable with an objective description of reality, 
to the !binding problem"  - how multifarious processes come together to convey the impression of a 
!Cartesian theatre" 19,20  of the mind.  
 
Figure 5: Expression of encephalopsin (Opn3), stoml3, otocadherin 
(Cdh23) and otoferlin (Otof) in the parietal cortex illustrate differing modes 
of cortical expression. 
 
Research into the biophysical basis of consciousness remains 
obscure, invoking a variety of speculative theories, few of which 
have convincing experimental support at the cellular level. 
Nevertheless subjective conscious states, from dreaming, through 
psychedelic states, to memory and imagination, each possess a 
veridical reality, which is of the same broad sensory nature as an 
external experience. Indeed dreaming can become all too real, by 
any sensory measure, despite attempts at lucidity checks! 
 
Although we conceive of the nominal five senses - vision, touch, 
hearing taste and smell - as biological adaptions, they are actually 
manifestations of the principal quantum modes by which an 
organism can interact with the physical world. Vision is photon-
orbital interaction, hearing comes somewhere between phonon-
orbital and the mechano-receptor dynamics of touch, taste and 
smell are traditionally defined as an orbital-orbital shape-fitting, 
although some research 29 suggests smell involves quantum 
vibration modes as well.  Sensory transduction is also capable of 
working at the quantum limit. Frog rod cells are capable of 
responding to single photons 26, pheromones likewise can elicit a response from a single molecule 
(especially in insects) and the limits of audition involve movements of the cochlear membrane of the 
order of a hydrogen atom radius 26,27.  
   
While the evidence presented is from distributed gene expression and thus in no way confirms these 
molecules are performing a sensory transduction function in the central nervous system, the theory  
does present an innovative and scientifically provocative biophysical hypothesis about the genesis of 
the !internal model", which could also have significant implications for cognitive science.  Physically 
transduced quantum excitations phase correlated with the electrodynamics underlying the 
electroencephalogram could provide a realizable means for the brain to generate quantum entangled 
states, permitting forms of quantum computing using our massively parallel, phase coupled brain 
dynamics.  Some models 27,28  also suggest such processes could also have an anticipatory function 
which might help explain free-will. 
 
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A stomatin-domain protein essential for touch sensation in the mouse

Casting a Genetic Light on the Evolution of Eyes Science 313:

Conformational dynamics and thermal cones of C-terminal tubulin tails in neuronal microtubules.

Consciousness Explained.

Consciousness, Neurobiology and Quantum Mechanics: The Case for a Connection, in &quot;The Emerging Physics of Consciousness&quot; Springer (Ed.) Jack Tuszynski

Craighero Laila

Dissipationless waves for information transfer in neurobiology - some implications.

Dreams, Memories, Reflections Random House,

Encephalopsin: A Novel Mammalian Extraretinal Opsin Discretely Localized in the Brain The Journal of Neuroscience,

Focusing on the genetics of hearing: you ain t heard nothin yet

Genome-wide atlas of gene expression in the adult mouse brain

In the Theatre of Consciousness: Global Workspace Theory, A Rigorous Scientific Theory of Consciousness.

Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.

Neuronic system inside neurons: molecular biology and biophysics of neuronal microtubules.

Otoferlin, Defective in a Human Deafness Form, Is Essential for Exocytosis at the Auditory Ribbon Synapse Cell

Quantum Computation in Brain Microtubules? Decoherence and Biological Feasibility Physical reviews E,

Quantum Cosmology and the Hard Problem of the Conscious Brain in &quot;The Emerging Physics of Consciousness&quot; Springer (Ed.) Jack Tuszynski

Quantum Mechanics, Chaos and the Conscious Brain.

The Alchemy of Culture

The Puzzle of Conscious Experience Scientific American

The Secret of Scent:

The taste of words on the tip of the tongue

Sensory Transduction and Subjective Experience: Expression of eight genes in three senses suggests a radical model of consciousness

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Sensory Transduction and Subjective Experience: Expression of eight genes in three senses suggests a radical model of consciousness

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