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
21
st
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 Atlas
1
) 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.
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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.
Nature Precedings : hdl:10101/npre.2007.1473.1 : Posted 29 Dec 2007
New Light on the Sensory Brain
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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 microtubules
12,13,14
, and others involving
coherent quantum excitations including a protein/water/EM field model
15,16,17,18
. 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
Nature Precedings : hdl:10101/npre.2007.1473.1 : Posted 29 Dec 2007
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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