What kind of functions and connections does the superior
colliculus have? In which part of the brain is it situated?
How are the visual fields of the two eyes represented in the
lateral geniculate body?
In which layers do the different subtypes of retinal
ganglion cells terminate? Answer in bullet points and highlight the most important words
Basic Principles of Sensory Physiology
Everything an animal or human being does depends on receiving and correctly interpreting
information from its external and internal environment. We all need accurate information about our
surroundings in order to know what to do now and what to do next. These decisions can only be
appropriate if the data collected from the environment are faithfully coded into signals that can be
received and processed by neurons in the brain. The sensory information, which provides the
respective information can be defined as neural activity originating from stimulation of receptor cells
in specific parts of the body. According to the source of signals two different classes of sensory
receptors occur:
Enteroreceptors: respond to signals from within the body such as blood pressure, oxygen
concentration, pH.
Exteroreceptors: collect signals from the outside world such as vision, hearing, touch etc.
The current course will focus onto exteroreceptors.
Based on cell structure two major subclasses of sensory cells can be distinguished**:**
primary sensory cells, which possess an axon and are able to generate action potentials and
secondary sensory cells which do not have an axon and hence transmit signals directly from their
cell body to target cells via synaptic transmission, similar as it otherwise occurs in nerve terminals.
While secondary sensory cells are quite common including cells sensing sounds and taste primary
sensory cells are mainly found in smell organs (sense of olfaction).
The types of sensory information we can discern are called sensory modalities. Sensory
organs usually are specialized to detect a certain modality**.** Their threshold of detection is low for
an adequate stimulus and very high for an inadequate stimulus. This is due to the fact that sensory
cells (also called receptor cells) in a given organ possess highly specialized structural and molecular
equipment that makes them selectively sensitive to one particular modality. Receptors cells are
prepared to capture the energy from a certain stimulus (e.g. light or mechanical vibrations), and
transform it into the language of nerve cells, i.e. electrical signals. During this process, which is
called signal transduction in most cases an enormous signal amplification is generated**,** allowing
the cells to respond to minimal energy quantities e.g. those provided by a single photon. Intracellular
amplification of sensory signals is often accomplished by complex enzymatic cascades, resembling
those occurring in postsynapses operating with metabotropic neurotransmitter receptors. The initialelectrical response of a sensory cell is called the receptor potential. Its size closely corresponds to
the strength of the stimulus to which the cell was exposed (graded potential). Depending on the
subtype of sensory cells involved (primary or secondary) the receptor potential induces either the
formation of action potentials or it directly initiates the release of neurotransmitters from the cell
body by exocytosis to hand over the information to a target neuron.
The response characteristic of a sensory cell can be described in a quantitative manner by plotting
the response size of the cell (e.g. size of the receptor potential) against the strength of the stimulus
applied to it. The resulting input/output diagram exhibits a typical sigmoid curve, consisting of three
major components:
• _an initial lag phase, during which the sensory cell gradually gets activated to finally
override a certain response threshold
• _a more or less linear working range, during which increases in stimulus strength are closely
mirrored by a corresponding increase of cellular response.
• _a saturation phase, during which the receptor potential will no longer increase.
It is obvious that faithful information about environmental stimulus strength is provided only in the
working range. A major challenge for any sensory organ thus is to combine high sensitivity (i.e.
low threshold of detection) with a large working range that allows the cell to faithfully monitor
the stimulus intensity over a wide range.
The quantitative relationship between stimulus intensity and the subjective experience of a test
person is studied by the science of psychophysics. In an early attempt to quantify subjective
experience E.H. Weber presented pairs of stimuli to test persons and asked them if they had
perceived a difference**.** By applying stimuli pairs of gradually lower intensity difference he could
thus determine the minimal increment (just noticeable difference) required for perception. By
performing these experiments over a wide range of stimulus intensities he noticed that the minimal
perceptible increment between two stimuli depends on the strength of the first (“standard”)
stimulus: at progressively higher stimulus intensities the discrimination sensitivity decreased. A
mathematical analysis of the data by Fechner revealed a logarithmic relationship between stimulus
strength and subjective experience (Weber – Fechner law). Later on, similar studies performed by
Stevens suggested that in many cases a power function more adequately describes the input/output
relationship, especially when low intensity ranges are included in the consideration. By such
relationships the working range of a sensory organ (or cell) can be most effectively extended over
several powers of ten**.** However, accurate measurement of absolute stimulus intensities is no longer
possible. Sensory cells are obviously designed to measure small changes in stimulus intensityrather than providing reliable information about absolute stimulus intensities. The lowest stimulus
strength a subject can detect is termed the sensory threshold.
How faithfully do receptor cells reproduce the timing of a stimulus? Three major classes of
response behaviours towards an ongoing stimulus can be distinguished among receptor cells:
Tonic receptors: fire continuously throughout stimulation, with increasing frequency at higher
stimulus intensity (proportional transducers).
Phasic receptors: are often active only during the onset or offset of a stimulus, they are most
sensitive for changes in stimulus intensity.
Phasic-tonic : initially onset/offset, later proportional response. This is a very abundant type of
receptor cell.
Many receptor cells show spontaneous activity, i.e. they exhibit (low) electrical signaling activity
even in the absence of stimulation. These receptors avoid the lag phase in their input/output
relationship (see above) and enter the working range immediately after receiving a stimulus thus
achieving a very fast response characteristic.
As it is most evident in the case of phasic receptors, sensory cells have an intrinsic capability for
adaptation. Given the enormous sensitivity of sensory cells adaptation is not only a mode of
information encoding but serves also to protect the cells against excessive stimulation. Adaptation
can take place at any level of the sensory cascade:
Filter level, accessory structures: (often in mechanoreceptors, closing of the eye pupil),
transient reaction, not sustained.
Transducer molecules :(e.g. bleaching of visual pigments) run down or inactivation of
receptor molecules
Enzyme cascade may become inhibited by the accumulation of an intermediate product,
feedback inhibition by second messengers such as cAMP
Electrical properties may change, e.g due to accumulation of free Ca
2+
, that leads to
activation of Ca
2+
-sensitive potassium channels.
The response characteristic of sensory cells is furthermore controlled by the network of neuronal
cells into which it is embedded. By connection with inhibitory interneurons the signaling activity can
be adjusted (reduced) to an appropriate level (feedback inhibition).
Often neighboring sensory cells are directly connected with each other via inhibitory interneurons
leading to lateral inhibition, which means that a local stimulation evokes inhibition of sensory cells
in the surrounding region. This generates a sharpening of sensory detection or increase of sensory
contrast.Visual reception
For man the sense of vision probably is the most relevant modality for orientation in his environment.
On a cellular level photoreception consists of transducing the energy of photons into electrical
signals that can be interpreted by the nervous system. Visible light comprises only a small fraction
of the broad energy spectrum covered by electromagnetic radiation. It includes wavelengths between
400 and 700 nm (visual spectrum), which appear as different colors when being perceived separately.
The human eye:
Eyes focus and collect light. They have structural features in common with a camera (lens eye). The
pupil forms a variable diaphragm, and the cornea and lens provide the refractive optics. Initially
refraction of light rays occurs through the cornea (exerting as much as 70% of the total refractive
power!). They are further bent by the lens and finally form an inverted image on the rear internal
surface, covered by the retina. This optical error is compensated in the higher visual centers.
Movements of the eye allow change and selection of the visual field. Three pairs of eye muscles
control movement of the eyeball, to select objects and/or to keep the visual field constant. Normally
eye muscles are constantly active to allow continuous screening of the visual field. Two types of
involuntary eye movements can be distinguished:
• _smooth pursuit movements in response to a moving object
• _saccadic movements, which are short sudden jumps made by the eye as it changes its point
of fixation. They occur continuously while scanning the visual world.
The activity of eye muscles is constantly controlled by oculomotor centers in the midbrain.
The function of the lens is to aid in focusing an image onto the retina. By changing the shape of the
lens its refractory power is adjusted to the distance of an object under observation, a process called
accommodation. The lens is surrounded by a ring muscle and is connected to it via radial oriented
ciliary fibers. When the ciliary ring muscle relaxes the lens becomes stretched by the ciliary fibres.
The flattened shape of the lens drives the focus on objects which are far away. Contraction of the
ring muscles leads to a relaxation of the ciliary fibers thus allowing the lens to passively return to its
more globular resting state with a high refractive power (near accommodation). Due to a loss of
water content the elasticity of the lens decreases with age, leading to long-sightedness. The ring
muscle is innervated by a parasympathetic nerve (mAchR). The muscarinic antagonist atropine
therefore causes relaxation of the ciliary muscle and hence far accommodation.The iris controls the amount of light entering into the eye bulb (adaptation). It serves to protect the
highly sensitive and delicate cells of the retina. The sudden closure of the pupils in response to light
exposure is due to the contraction of the sphincter muscle in the iris (fast iris reflex). It is initiated
by a cholinergic parasympathetic nerve that innervates this muscle. Application of atropine blocks
the iris reflex, allowing medical inspection of the eye background. In the dark sympathetic
innervation of the antagonistic dilatator muscle slowly reopens the pupils adapting the eye to low
amounts of light. These reflexes of the iris are coordinated in the midbrain (see also: visual pathway).
Cellular structure of the retina
The retina is a part of the central nervous system, since during embryonic development it forms as
an extension of the diencephalon (interbrain). It contains a fairly limited number of cell types
arranged in a highly ordered network of interneurons. The outermost layer of cells harbours the
photoreceptor cells which are surrounded by the pigment epithelium that supports the
photoreceptors and shields them from light. Visual signals captured by photoreceptors are transferred
in a radial direction to bipolar cells which in turn are connected to retinal ganglion cells. Their
axons collectively form the optic nerve which exports visual signals to target neurons in the brain
(the area, where the optic nerve leaves the retina is called the blind spot, because it contains no
photoreceptors). In addition two horizontal paths of information processing occur in the retina,
which are carried by horizontal and amacrine cells, respectively. While horizontal cells mediate
lateral contacts between photoreceptor cells, amacrine cells interconnect bipolar cells and retinal
ganglion cells (for functional circuitry see below).
Photoreceptor cells occur in two major subtypes called rods and cones, which were named according
to their shape as seen under a microscope. These cells absorb light and convert it into a neural signal,
an essential process known as phototransduction. The photosensitive part of the cells is called the
outer segment. In the case of rods it is filled with flat membrane disks that contain the visual
pigment rhodopsin. Cones have a pleated outer plasma membrane instead. Both cell types have a
unique presynaptic structure called synaptic ribbon, which attracts synaptic vesicles ready for
collective exocytosis (“compound fusion”). Rods and cones differ functionally from each other, in
that rods are highly specialized for dim light vision, while cones are properly operating only under
good illumination condition since they are by far less light sensitive than rods. Cones are able to
discriminate wavelengths and hence are responsible for color vision. Both photoreceptor types are
unevenly distributed in the retina: cones are highly concentrated in the center (fovea), the region of
highest visual acuity, while rods are predominating in the peripheral region and are much more
abundant in the retina than cones. Objects presented to a test person at the outer rim of the visualfield therefore are seen in grey scale not giving any color impression. Another difference is related
to the connectivity pattern between photoreceptors and retinal ganglion cells: while cones in the
fovea are connected to retinal ganglion cells in a 1:1 relationship, in the case of rods more than
1000 cells are synapsing onto a single retinal ganglion cell. This strongly convergent circuitry
significantly adds to the high light sensitivity of the rod visual pathway.
The visual process
Electrophysiological recordings have revealed that the membrane potential of photoreceptors
becomes hyperpolarized to about -80 mV in the presence of bright light, while in the dark it
repolarizes to -30mV. This is due to a so-called dark current, a continuous influx of cations (mostly
calcium and sodium) into the outer segment in the absence of light. This current is equilibrated by
a potassium efflux at the cell body. Upon illumination the cation-channel in the outer segment closes
and the ongoing potassium efflux at the cell body hyperpolarizes the membrane potential. Under
these conditions no neurotansmitter release will occur at photoreceptor synapses.
On a molecular level the visual pigment rhodopsin operates as receptor molecule that captures the
energy of photons. It is composed of a seven-transmembrane protein called opsin to which the
photosensitive pigment molecule 11-cis retinal is chemically fixed. The basic molecular structure of
rhodopsin is reminiscent of a metabotropic neurotransmitter receptor. In further similarity rhodopsin
is coupled to a G-protein, in this case named transducin, to emphasize its key role in the process
of visual signal transduction (phototransduction).
The primary chemical reaction of rhodopsin to light is a structural switch within the hydrocarbon
chain of 11-cis retinal converting it to an intermediate state, metarhodopsin II, which triggers the
second step of phototransduction. Metarhodopsin II is unstable and splits within minutes, yielding
all-trans retinal. The all-trans retinal is subsequently split off from the opsin protein and transported
into pigment cells for regeneration. Within the pigment epithelial cell, the all-trans retinal is reduced
to all-trans retinol (vitamin A), the precursor of 11-cis retinal, which is subsequently transported back
to rods. A nutritional deficit of this vitamin causes night blindness and in if untreated, to deterioration
of receptor outer segments and eventually to blindness.
The conversion of 11-cis into all-trans retinal leads to defined conformational changes in the opsin
protein, which ultimately causes dissociation and release of the G-protein complex. As is the case
for other G proteins, the inactive form of transducin binds a molecule of guanosine diphosphate
(GDP). Interaction with metarhodopsin II promotes the exchange of GDP for guanosine triphosphate
(GTP). The liberated α**-subunit** of this complex activates the enzyme phosphodiesterase inside the
outer segment by forming a complex with it**.** The substrate of this enzyme is the second messengermolecule cGMP (cyclic guanosine monophosphate a close relative of cAMP). In the dark cGMP
binds to the cation channel mentioned above and keeps it open. The channel is therefore classified
as a cyclic-nucleotide-gated channel (CNG-channel). In the light the activated phosphodiesterase
splits cGMP into 5’-GMP, leading to the closure of the CNG-channel, which causes the
electrophysiological effects described above.
In the dark cGMP is reformed leading to an opening of the CNG-channel. The complex enzymatic
cascade leads to enormous signal amplification since for every rhodopsin activated by light
hundreds of G-proteins become activated. Furthermore, every molecule of phosphodiesterase will
split more than 1000 cGMP molecules leading to a high degree of amplification.
Neuronal circuitry:
As mentioned above visual signals are transferred onto retinal ganglion cells via radial oriented
bipolar cells (radial signal transfer). While in the dark there is a constant release of glutamate at
photoreceptor synapses, in the presence of light hyperpolarization of the membrane potential
terminates neurotransmitter release (see above). Accordingly bipolar cells will be exposed to
glutamate only in the dark.
In the cone pathway electrophysiological recordings surprisingly reveal two different
subpopulations of bipolar cells with opposing responses to a light signal: off-bipolar cells become
hyperpolarized much like cones, while on-bipolar cells become depolarized under illumination. This
is due to the presence of ionotropic glutamate receptors in off-bipolar cells (excitatory synapse)
and of metabotropic glutamate receptors in the case of on-bipolar cells (inhibitory synapse).
Accordingly two types of retinal ganglion cell (RGC) responses are found: RGCs being connected
with on-bipolar cells show an increased firing frequency (on-RGC) while RGCs being connected
with off-bipolar cells decrease their firing rates under illumination. (RGC show spontaneous firing
activity, hence their response to light is either an increase or decrease of firing frequency).
In the rod pathway only on-bipolar cells are engaged. Nevertheless there is an on- as well as an off-
response in RGCs connected to rods. Depolarization of rod on-bipolar cells is evoked through
metabotropic glutamate receptors just as described above for cones. The off-response of RGC is
mediated via amacrine cells that release the inhibitory neurotransmitter glycine to dendrites of
RGCs, leading to hyperpolarization of these cells. Electrical synapses between amacrine cells and
RGCs on the other side maintain the on-response of RGCs in the rod pathway.
Horizontal cells play an important role in the lateral (horizontal) signaling pathway in the retina.
They are connected to neighboring photoreceptor cells and in the dark release the inhibitory
neurotransmitter GABA. If a photoreceptor cells becomes stimulated by a light spot its neighborswill become indirectly influenced via horizontal cells: upon hyperpolarization by the illuminated
photoreceptor horizontal cells will reduce their GABA-release, thus reducing their inhibitory effect
on neighboring photoreceptors. If these are lying in dim light their depolarization and transmitter
release will further increase. By this process response activities at light/dark borders become
enhanced (sharpening of contrast due to lateral inhibition).
Retinal ganglion cells (RGC)
The total number of photoreceptors connected to a retinal ganglion cells constitute its receptive field.
The receptive field size closely correlates with the size of the dendritic tree. By moving a small spot
light over the receptive field, a typical change in the firing behavior of a RGC can be observed. When
the spot is localized in the center either an increase (on-center RGC) or a decrease in firing
frequency is observed (off-center RGC). As the spot reaches the periphery of the receptive field the
firing behavior changes into its opposite, i.e. in the case of on-center cells the firing frequency drops
if the periphery is illuminated, while in the case of off-center cells it increases (center-surround
antagonism). Clearly this effect is due to lateral inhibition by horizontal cells.
The population of retinal ganglion cells can be further subdivided on the basis of structural criteria:
alpha-cells (also called M-cells) are largest, having a wide dendritic tree, while beta-cells (also
called P-cells) are significantly smaller. Gamma-cells are a heterogeneous population of more
irregular cell shape. Alpha cells are specialized to detect coarse structures and movement of objects,
while beta-cells are involved in fine detail analysis and color vision.
Color vision:
Two opposing theories about color vision were established in the 19
th
century:
• _the trichromacy theory proposed by Young (reinforced later by Helmholtz) claims that three
primary colors (red, blue and green) are sufficient to produce all other colors. In fact three
distinct classes of cones with overlapping absorption spectra do exist: at a molecular level color
sensitivity arises from about 15 amino acid differences in the membrane spanning segments of
the opsin proteins. Inherited color blindness is therefore caused by an absence or a defect in one
of the opsin genes. Note: overlapping spectra are necessary to distinguish wavelength
differences from light intensity differences. Example: a higher proportion of red light
hyperpolarizes red cones stronger than blue cones, while a higher illumination level
hyperpolarizes both to the same extent. The theory is consistent with experiments of additive
color mixture (slide projector experiment: mixed red and green light produces yellow).Subtractive color mixture: in this case color impression is brought about by absorption: blood
is red because the blood pigment absorbs the green component of white light (so do color
pigments of painters).
• _the color opponency theory (Ewald Hering) explains color coding at the level of ganglion cells
and higher brain regions: Experiment: if we look for few minutes on a red surface and then look
at a neutral white we will see a green after-image. The same is true for blue and yellow (opponent
colors). The signals coming from the three types of cones are combined on the level of ganglion
cells in an antagonistic manner: three antagonistic channels exist: red-green, blue-yellow, black-
white. Color-selective ganglion cells in the retina possess receptive fields with the same color
opponency. One group has a red-green opponency, a second group is blue -yellow-sensitive
Yellow-blue opponency is generated by adding the signals coming from red and green cones
(yielding yellow) via red-green bipolar cells to the center of the receptive field, while blue cones
are connected via blue bipolar cells to the periphery of the dendritic tree of the same RGC.Visual processing and perception
Evolution of the visual pathway
The axons of the retinal ganglion cells are routed either to the contralateral (= opposite) or to the
ipsilateral (= the same) side of the brain, they cross the midline at the level of the optic chiasm. The
degree of crossing varies in different animal species. In lower vertebrates such as fish there is a total
decussation of both nerves: in these animals the eyes are set on the side of the head and hence there
is very little overlap of the two visual fields. In most mammals including man the crossing is only
partial (see also below: the human central visual pathway). In the fish brain the retinal axons directly
travel to a primary visual center in the dorsal part of the midbrain (mesencephalon), termed the optic
tectum. The function of this region gradually changes during evolution. In mammalian species this
brain region is no longer acting as a primary visual center but acts as a coordination center for eye
movements and it receives only about 10% of the retinal ganglion cell axons. The region of the
tectum during evolution becomes divided into two functionally different parts, the colliculus
superior (oculomotor input) and the colliculus inferior, which receives auditory input. Efferent
fibers from the colliculus superior indirectly innervate the three pairs of eye muscles which control
the position of the eyeball and hence the position of the visual field (direction of gaze, nystagmus to
keep the visual field constant, visual field selection). In spite of eye or head movements we perceive
a stable visual scene, which is coordinated by neuronal connections between oculomotor centers in
the midbrain and higher visual centers in the cortex.
Furthermore the colliculus superior acts as a multimodal interface, where sensory information from
various modalities converges and can be compared. Thus, a moving object detected by vision or
hearing can be followed by movement of the eyes and/or the head. Eye movements can be elicited
by moving acoustic stimuli as well.
The human central visual pathway
In humans the eyes are set forward in the head, and the two visual fields strongly overlap. Associated
with this is only a partial decussation of the optic nerve. The ipsilateral fibers are those that arise
from the outer (temporal) half of the retina, which receives stimuli from the inner (nasal) half of the
visual field. The fibers on the inner (nasal) half of the retina by contrast decussate at the optic chiasm
and terminate in the contralateral visual centers. By this arrangement stimuli from one half of the
visual field -as seen under slightly different angles by the two eyes- are collected in the same brain
hemisphere. This is an important prerequisite for stereoptic 3D-vision. As will be pointed out below
this process is initiated in the primary visual cortex.Lateral geniculate body
The majority of retinal axons (90%) travel to the thalamus in the diencephalon. Since nearly every
sensory fiber terminates in that region the thalamus has an ordered structural segregation into
different subregions. The retinal fibers terminate in a region called the corpus geniculatum laterale
(CGL, lateral geniculate body, seitlicher Kniehöcker). As should be expected their synapses are
excitatory, the neurotransmitter is glutamate. There is a precise topographical representation of the
retinal image on the level of the thalamus (topographical map, point-to point projection) and both
visual fields are still separated from each other. Each lateral geniculate body receives input from only
one half of each visual field (see also human central visual pathway). Target neurons in the CGL
still have concentric receptive fields, resembling those of retinal ganglion cells. The CGL is
subdivided into six parallel layers, which receive a highly ordered input from different types of
ganglion cells located in different retinal regions. The top four layers contain neurons with smaller
somata, hence they are called parvocellular layers, while the bottom two layers contain larger
neurons (magnocellular layers). The 4 parvocellular layers are connected with beta-cells in the
center of the retina, while the two mangocellular layers are in synaptic contact with alpha-cells in the
retinal periphery. Hence the representation is not linear, the central region of the retina is highly
overrepresented. At the level of the CGL the visual pathway is split into a nasal contralateral
branch terminating in layers 1, 4 and 6 and a temporal ipsilateral branch terminating in layers 2,
3 and 5 (this is important for stereopsis and depth perception in the primary visual cortex, see below).
Within each layer the topography of the retinal map is exactly preserved.
In addition to this initial sorting and parallel processing of different visual cues, filtering of
sensory signals by inhibitory GABAergic interneurons takes place in the CGL (thalamo-cortical
gating). The latter is controlled by a strong feedback projection originating from layer 6 of the
primary visual cortex (see below). The thalamo-cortical relay cells that transport the visual signals
into the cortex are under the inhibitory influence of GABAergic thalamic reticular neurons.
Depending on the state of attention relay neurons can switch between two different types of response
activity: in the highly attentive state they exhibit regular spiking activity (tonic firing of action
potentials), while in the sleeping mode they switch into a rhythmically bursting mode. The latter
mode is supported by low threshold voltage-gated calcium-channels, that open in response to a
synaptic membrane hyperpolarization (ipsp) and elicit a slow wave of depolarization. After a certain
level of depolarization is reached voltage-gated sodium channels are additionally opened as reflected
by the ensuing burst of action potentials. The accumulation of calcium inside the cell subsequently
opens calcium-sensitive potassium channels that repolarize the plasma membrane again.The primary visual cortex
The primary visual cortex is located in the occipital lobe. It is also called striate cortex, V1 or area
17 (according to Brodmann). As all other cortical fields it is composed of six cellular layers. Layer
4 is the target region for visual fibers coming from the CGL. Stellate cells residing in this layer are
their primary target neurons. They in turn synapse onto pyramidal cells, which have their cell bodies
in layer 5. A considerable number of them further project to pyramidal cells in layer 6, which project
back to the CGL.
Functional organization of the visual cortex
Experiments done by Hubel and Wiesel in Kufflers lab (Noble prize in 1981) on cats provided
fundamental knowledge about visual processing in the visual cortex. They presented to living cats a
variety of simple visual stimuli such as spots and bars in various angular orientations as well as
moving objects on a screen and recorded the electrical responses of cortical neurons through
implanted electrodes. By systematically penetrating the recording electrode through the thickness
of the primary visual cortex they could characterize the response activities of cells in different cortical
layers. A major surprise was that the responses of these neurons were quite distinct from those in the
retina and CGL, in that they were most sensitive to bars and straight borders in different
orientations. If the electrode was penetrated strictly perpendicular to the cortical surface all cells
had the same angular orientation preference. If the adjustment of the electrode was tilted
somewhat, the angular orientation preference gradually changed as the electrode went deeper. The
experimenters concluded that the cortex was functionally organized into laterally aligned columns,
each preferring a different angle of bar orientation, thereby discriminating approx. 10° (orientation
columns, 50 μm width). The cellular basis for this observation is a convergent connection between
stellate cells in layer 4 (which still have concentric receptive fields) and simple pyramidal cells. The
overlapping receptive fields of individual stellate cells are thus collected on a target neuron. Hence
each simple cell receives excitatory input from CGL cells (via stellate cells) whose on-centers are
linearly aligned on the retina. Due to the summation of epsps a simple cell is maximally activated if
light falls exactly on these receptive fields. End-inhibition (or double end-inhibition) allows
discrimination of bar length, e. g. by feedback loops from layer 6 pyramidal cells that project back
via GABAergig interneurons.
Complex cells have still larger receptive field sizes and constitute the next level of abstraction in
visual processing. Their responses are probably based on the pattern of innervation they receive from
simple cells. Like those they respond best to borders of different angular orientation. Unlike simple
cells they do not have topographically fixed receptive fields but respond rather independent from theposition in the visual field. Some detect edges (convergence of simple cells with 90 degree
orientation) or other geometrical structures (analysis of the contours of an object). Others respond
maximally to borders moving into one direction but not into the other (directionality).
Ocular dominance columns
By injecting radioactively labeled amino acids into one eye nerve fiber connections can be
visualized in the microscope. The amino acids are taken up by retinal ganglion cells and transported
via the optic nerve to their nerve endings (fast axonal transport). Target neurons in the CGL take up
the labeled material and further transport it to the visual cortex (transneuronal transport). The
distribution of radioactivity can be rendered visible on tissue slices if a thin photographic film is
placed over the sections, which is subsequently developed photochemically. With this method ocular
dominance columns (approx. 500μm stripe width) were identified which are alternately connected
to the left or to the right eye. This regular arrangement allows for a detailed comparison of visual
disparity angles as required for stereopsis.
Blobs in the visual cortex
Another means to identify functionally specialized areas in the visual cortex is the histochemical
localization of the mitochondrial enzyme cytochrome oxidase by specific staining methods. In tissue
sections performed in a plane parallel to the cortical surface this enzyme is found highly accumulated
in layers 2 and 3 of the primary visual cortex in regularly arranged clusters (so-called blobs).
Electrophysiological recordings revealed that color-sensitive target neurons are grouped together in
these blobs.
The visual pathway is separated from the beginning into several parallel streams, e.g the
magnocellular and the parvocellular path, both of which can be clearly pursued in the lateral
geniculate body (layers 1-2 = magnocellular, layers 3-6 = parvocellular) and further traced in the
primary visual cortex (blobs = parvocellular path, interblobs = magnocellular path). Moreover they
both separately project further into the adjacent cortical areas (V2-V5): area V4 being specialized for
color vision is an extension of the parvocellular system, while area V5, being specialized to motion
detection, is part of the magnocellular system.
Projections to higher cortical areas
From the occipital cortex the visual pathway splits into two major projections performing even more
complex pattern analysis:
The parietal where pathway which is specialized for
• _motion detection, stereoptic vision, connections with the oculomotor centers in thebrainstem provide spatial constancy of the visual field.
• _multisensory integration (hearing, vision, somatic)
• _space perception (visual hemineglect as a consequence of stroke in the right parietal
cortex).
The temporal what pathway being specialized for
• _object recognition and visual memory
• _visual recognition of faces (prosopagnosy due to a lesion in the temporal cortex:
patients are unable to recognize a person from its face but still recognize it by voice).
Cerebral dominance/ split brain
The two cerebral (cortical) hemispheres show a marked functional asymmetry in that each of them
has a specialized mode of cognitive task performance. This was revealed in studies with so-called
split-brain patients, where the major connection between both cerebral hemispheres the corpus
callosum had been transected surgically in order to limit the spreading of epileptic convulsions.
Specific test conditions are required to identify functional specializations of both hemispheres: the
test person fixes two separate screens, where an object is presented for a tenth of a second. The test
person cannot see its hands. It identifies the object either verbally or non-verbally (e.g. by selecting
objects with one hand).
The left hemisphere turned out to be specialized for language analysis, writing and reading, doing
calculations.
The right hemisphere turned out to be specialized for spatial construction, geometrical pattern
analysis, nonverbal ideation, emotional touch and music perception.Hearing
The human ear includes two types of sensory organs:
• _organs of equilibrium (reporting about the position and acceleration in space)
• _organs of hearing (reception of sound waves, airborne vibrations).
Physically speaking sound is a mechanical vibration (oscillating air pressure), which propagates
through the air or water.
The human auditive spectrum is limited by
• _frequency range: 20 Hz – 16 kHz
• _loudness range: 0-130 db, spanning between threshold of audibility and threshold of pain
(subjective perception is measured in decibel on a log scale).
Loudness sensitivity is highly dependent on the sound frequency. Highest sensitivity is in the
range of 2000-4000 Hz.
The external ear/ auditory canal
The external ear acts as a funnel that collects and directs sound waves to the eardrum (tympanic
membrane). It amplifies sounds in a particular frequency range and has a directional selectivity.
The middle ear
Airborne vibrations must be transmitted to the fluid filled inner ear. Most of the energy generated
in the air is reflected back from the water surface. This problem is called „acoustic impedance
mismatch“. It is partially overcome by three small bones connected in series that are attached at one
end at the eardrum and at the other at the oval window of the cochlea. Mechanical coupling of the
three auditory ossicles (hammer, incus, stapes) amplifies the signal by a factor of 1.3. Since the size
of the eardrum area is about 17 fold larger than those of the oval window, the sound pressure is
concentrated on a smaller area, leading to a total amplification factor of at least 22. The auditory
ossicles can also reduce sound pressure, e.g. in case of very loud sounds, by uncoupling each other
through particular muscles. Note: the inner ear is very sensible against overstimulation!
The inner ear/ cochlea
The human cochlea is a tapered tube that is coiled into a spiral resembling the shell of a snail. It
contains the organ of Corti. The inside of the tube is separated into three longitudinal compartments:
The two outer compartments (Scala tympani, Scala vestibuli) are connected via the helicotrema,an opening at the apex of the cochlea. Sound waves travel back through the Scala tympani and leave
the cochlea through the round window. Both are filled with perilymph fluid. Between these
compartments is another compartment, the Scala media, which is filled with endolymph fluid.
Boundaries are the Reissner membrane and the basilar membrane.
• _Perilymph: high sodium, low potassium concentration, as normal.
• _Endoplymph: high potassium, low sodium, very particular, contributes to auditory transduction
(see below)!
Sound input is transduced into neuronal signals by hair cells (secondary sensory cells) that are sitting
in four rows on the basilar membrane (each row with about 4.000 cells). They are covered by the
tectorial membrane consisting of gelatinous mucus (the term membrane used here must not be
confused with the plasma membrane of cells!!)
Hair cells are elongated in shape with a distinctive arrangement of hairs, termed stereocilia (30-
100). The entire collection is the hair bundle. Hair cells occur in two different suptypes:
• _Inner hair cells : form a single row of cells, perform sound detection, are connected synaptically
with 90% of the auditory nerve fibers coming from the spiral ganglion.
Each hair cell receives numerous afferent nerve fibers. They have no direct contact with the
tectorial membrane.
• _Outer hair cells: form three rows of cells, are connected with only 10% of the afferent fibers,
but receive strong efferent input instead from the upper medial oliva. Are able to modulate and
amplify the sensitivity of sound reception by modifying the mechanical coupling between inner
hair cells and the tectorial membrane. The cells can contract or relax in response to their sensory
input. 1000 fold signal amplification by rhythmic cell contraction (up to 20 000 times per
second). Sharpening (focusing) of the traveling wave to a local maximum. Below 60 db the
endolymph stream alone is too weak to stimulate the inner hair cells. The protein prestin in the
lateral membrane of outer hair cells acts as a direct voltage to force converter, allowing
extremely fast cell contractions.
Hair cells respond to a specialized form of mechanical stimulation (stretch or distortion). The cilia
are bent by shearing forces that arise when the hair bundles (individual cilia are connected to each
other by tip links) move against the tectorial membrane.
Mechanical displacement of a hair bundle causes an extremely rapid depolarization (40 μs latency
period_)_ due to the opening of mechanosensitive ion channels, which respond independently from any
enzymatic signal transduction cascade.Though the cation channel has only a weak ionic selectivity (Na, K), the high extracellular potassium
concentration in the endolymph drives potassium influx to elicit membrane depolarization.
Opening of voltage-gated calcium channels at the cell base evokes neurotransmitter release by
exocytosis of synaptic vesicles. The transmitter is glutamate. Repolarization of hair cells is achieved
by voltage-gated potassium channels in the lateral membrane leading to potassium efflux into the
perilymph fluid.
Frequency analysis
The major factor that determines the tuning curve of an individual hair cell is its position in the
cochlea. The sheets of hair cells and supporting cells extend from the base of the spiral to its apex.
The mechanical design of the basilar membrane (more thick, stiff and narrow at the base versus
more elastic, broad and thin at the apex), coupled with the fact that changes in the thickness of the
tectorial membrane occur along its length, provides a mechanism for the selective response of hair
cells to different frequencies of sound. As was first suggested by the German physicist Helmholtz
more than hundred years ago**, high frequency sounds** cause the greatest vibrations to occur at the
base of the cochlea (due to different mechanical properties along the length of the basilar membrane).
By contrast low frequency sounds maximally deflect hair cells in the apex. In response to a pure
sine wave tone, the perturbations of the basilar membrane have the same frequency as the tone. Low
frequency perturbations move as traveling waves along the whole length of the basilar membrane,
from the narrow base to the wide apex (gradient of stiffness). The extent of membrane displacement
(maximally 1 μm) at any point along the basilar membrane determines how strong the hair cells are
stimulated.
Loudness
• _Louder sounds have less spatial selectivity on the basilar membrane, weaker sounds have a
are more restricted localization. Loudness is heard at the shallow end of the envelope
triangle (more close to the base) of a traveling wave. Frequency discrimination is
performed at the steep end (more close to the apex).
• _The number of activated nerve fibers recruited per inner hair cell increases with stimulus
intensity. Auditory fibers with identical best frequencies have different response thresholds
(dynamic range extension).
Tuning curves describe the sound pressure required to produce a certain change in membrane
potential at various sound frequencies („best frequency curve“). The slopes of these curves areoften more shallow at lower frequencies and steeper at higher frequencies. The threshold is frequency
dependent! Tuning curves reflect the receptive field of different frequencies.
Outer hair cells are extremely sensitive and hence vulnerable to over stimulation, which can cause
rupture at the base of the stereocilia. Acoustic trauma can cause permanent loss of hearing of a
particular frequency range.
Frequency analysis in the auditory nerve
• _For sounds up to 1 kHz: action potentials in the auditory nerve appear to follow the
fundamental frequency. In the nerve fibers the periodicity of bursts reflect the length of a sine
wave (phase locked stimulus response). The discharges of acoustic fibers are synchronized
with the phase of the tonal stimulus.
• _Above this level the time constants of the hair cells and the electrical properties of the axons
prevent a one-to-one correspondence between sound waves and electrical
signals. At higher frequencies the phase periodicities of several nerve fibers of a given hair
cells encode the wavelength of a sound.
Central auditory processing
Nucleus cochlearis
Auditory fibers are connected to neuronal cell bodies in the spiral ganglion (first order neurons). The
axons of its bipolar neurons join the 8th cranial nerve and project to the Nucleus cochlearis (first
relay of the auditory pathway) in the brainstem (medulla oblongata), where the auditory pathway
splits into three major paths.
• _a slow dorsal „what“–path, responsible for pattern analysis, that goes directly to the
contralateral colliculus inferior in the midbrain
• _a fast ventral „that“-path that gives a pre-warning to the colliculus inferior
• _a ventral „where“-path to the superior oliva (sound localization)
The cochlear nucleus contains a heterogeneous population of second order neurons that are
responsible for the transformation of sound signals. The various cell types often reside in typical
subregions of the nucleus cochlearis and possess cell type specific response patterns:
• _bushy cells and octopus cells in the ventral region often generate an “on-response” maintaining
a high temporal precision even at higher sound frequencies.
• _stellate cells of the ventral part often show a “chopper response”, reflecting rhythmicity ofsounds.
• _pyramidal cells in the dorsal part typically exhibit “build-up” or “pauser responses” providing
for a differentiation of the onset and ensuing phases of responses.
Each auditory nerve fiber splits into numerous branches and has multiple representations in the
cochlear nucleus thereby projecting onto various cell types. Thus a conversion of the input signal
into various different output responses takes place (each being an abstraction of one particular feature
of the auditory input signal).
The high variability in response types, tuning curves and intensity functions among different cells
types in the nucleus cochlearis is partly due to intrinsic firing properties of the cells and partly due
to network functions such as excitatory and inhibitory convergence.
Superior olivary complex The superior olivary complex consists of two major subdivisions, the
medial superior oliva (MSO) and the lateral superior oliva (LSO), both contributing to sound
localization in the brainstem: in the superior oliva informations from both ears converge, allowing
binaural sound localization (where pathway). Binaural localization of a sound source is basically
determined by measuring
• _temporal delay of sound waves arriving sequentially at both ears (minimal perceptible delay is
10 microseconds corresponding to 1-3° angle difference between both ears). This works best at
low frequencies up to 1.5 kHz. It takes place in the medium superior olivary nucleus (MSO).
Target neurons with identical best frequencies operate as coincidence detectors using a delay
line circuitry: thereby the different relative lengths of axons from the two cochlear nuclei to the
MSO act as temporal delay lines, that compensate for the delayed arrival of sound waves.
• _at higher frequencies sound pressure differences of sound waves from both ears are used for
sound localization (in the horizontal plane down to 1 dB discrimination) in the lateral superior
olivary nucleus (LSO). The majority of units are ipsilateral excitatory and contralateral
inhibitory, generating a subtractive response. The strength of inhibition varies topographically.
Colliculus inferior
The inferior colliculus in the midbrain performs simple auditory processing without memory
formation. It lies in the middle of bottom-up and top-down processing of the auditory system. It has
an onion-bulb pattern of isofrequency planes (tonotopy) that are piled up upon each other in discrete
cellular layers. A plane corresponds to a place on the basilar membrane. Within each plane target
neurons are arranged in isophone lines. Neurons with highest sensitivity are found in the center those
with lower sensitivity reside in the periphery.Auditory cortex (auditory memory formation)
The main thalamic relay nucleus for auditory information is the medial geniculate nucleus. The
thalamic relay neurons directly project into the primary auditory cortex (A1), which is hidden in
the depth between the sulcus lateralis and the sulcus centralis of the temporal lobe. It is organized
in isofrequency stripes containing neurons with identical best frequencies (tonotopic
representation). Each of these stripes is subdivided into regions with different loudness thresholds
and response bandwidths. Furthermore several overlapping neuronal maps can be discerned for each
isofrequency stripe that are specialized to detect:
• _speed or direction of frequency modulation (ascending : upper and lower laminae, or descending
tone: middle lamina)
• _shape of intensity curve (intensity function)
• _latency
• _response speed
Typically these maps have no continuously ordered structure but show an irregular scattered
arrangement (patchy maps). Thereby the same neurons can be engaged in different maps.
From the auditory cortex two major pathways (dorsal path, ventral path) of more complex
information processing project into separate areas of the prefrontal cortex. It has been suggested that
they are specialized for spatial correlation (where-pathway) and auditory object recognition (what-
pathway), respectively, similar as it occurs in the visual pathway.
Sense of balance
In most animals information about body and limb position as well as muscle length and tension is
indispensable for maintaining balance and movement control. The sense of equilibrium (balance) is
localized in the inner ear. It closely cooperates with other sensory modalities, in particular with the
proprioceptive system that monitors the length and tension of muscles.
Semicircular ducts
The semicircular ducts consist of three tubes filled with endoplymph fluid that are arranged
perpendicular to each other. They harbour the sense of rotation. At the base each ducts is widened
into an ampulla. In the wall of the ampullae there is a patch of sensory cells. Their hairs extend into
a gelatinous mass, called cupula, which extends into the endolymph fluid and acts like a swinging
door. If a semicircular duct is gently rotated, e.g. by a head movement, the cupula will become tilted
against the endolymph fluid which remains stationary due to its physical inertia. Ensuing deflectionof the hairs will open mechanically gated ion channels, similar as in the inner ear. If the rotation
persists over longer time, the endolymph starts to rotate at the same speed, which brings the cupula
back into a resting position. A sudden stop of rotation will bend the cupula into the opposite direction,
eventually leading to dizziness. Hair cells are directionally sensitive in that movement of the hair
bundle towards the longest hair (kinocilium) depolarizes the cell, whilst movement in the opposite
direction produces a hyperpolarization. The changes in membrane potential are caused by the
opening and closing of mechano-sensitive ion channels in the hair membrane
Macula organs (Utriculus, sacculus)
They harbor the sense of gravity and of linear acceleration. In both cases a field of hair cells is
covered by a gelatinous mass into which otokonia (calcit-cristalls containing calcium carbonate**)**
are embedded near the tips of the hairs. During sudden movements the otokonia lag behind, thus
deflecting the hairs into the opposite direction. At rest the otokonia simply follow gravitation (often
both forces will act together).
The orientation of the utriculus is horizontal, while those of the sacculus is vertical.
The vestibular pathway
The 19,000 nerve fibers of each vestibular nerve (part of 8th cranial nerve) have their cell bodies in
the vestibular ganglion near the membranous labyrinth (bipolar nerve cells). Their axons project to
the four vestibular nuclei in the medulla. From there a direct connection with the cerebellum exists.
Collateral fibers from the vestibular pathway system to the medullary reticular formation are
integrated into the activities of the reticular system. These connections may be involved in producing
symptoms of motion sickness (nausea, vomiting, sweating) due to excessive stimulation of the
vestibular system.
In the cerebellum information converges also from muscles via an afferent path to the spinal cord:
tractus spino-cerebellaris, which is famous for its extremely fast conduction velocity (more than
100 m/sec). See also next topic: proprioceptors.Proprioceptors
They monitor the position of muscles and joints. They tell you where your limbs are and what they
are doing. They measure mechanical forces.
• _Tension receptors: Golgi-tendon fibers (Ib-fibers), which measure the tension in the
muscles (serial arrangement with muscle fiber). They synapse onto α-motoneurons via
inhibitory interneurons (to maintain muscle tension if the tendon becomes relaxed), a
collagenous fiber network surrounds the nerve endings.
• _Stretch receptors: muscle spindles being arranged in parallel with muscle fibers measure
the length of a muscle. They are modified muscle fibers (intrafusal fibers), which in their
central part are surrounded by free nerve endings belonging to pseudo-unipolar sensory
neurons in the dorsal root ganglia (Ia- fibers). They respond to a passive stretch stimulus
with phasic-tonic discharge. They control the length of muscle fibers via a feedback loop:
α**-motoneurons** in the spinal cord become activated and compensate the passive stretch by
muscle contraction (mainstay reflex).
Voluntary movement control
To enable voluntary muscle contraction during movements the mainstay reflex has to be
overcome: efferent γ**-fibers** from small γ**-motoneurons** in the spinal cord innervate the
contractile portions of muscle spindles that flank the central mechano-sensitive region of the
intrafusal fibers. Activation of γ**-motoneurons** can thus initiate a stretching stimulus of the
muscle spindula (pretension). This allows muscle contraction until the pretension in the muscle
spindle is compensated. Hence the available degree of muscle contraction elicited by α-
motoneurons is controlled by the activity of the γ**-fibers**.
Movement Control in the Cerebellum
The cerebellum exerts movement control by comparing afferent (sensory) information with
corresponding efferent signals from the motor cortex (both conveyed to the cerebellum via
parallel fibers, see below). If there is a sensory-motor mismatch the cerebellum sends out
correcting signals via Purkinje cell axons that have GABAergic nerve terminals. The
cerebellum is strongly engaged in motor learning. The two most prominent pathways that
deliver signals to Purkinje cells are the climbing fibers and the parallel fibers. The latter are
the axons of granule cells in the cerebellar cortex. They outnumber any other neurons in the
human brain. Their axons bifurcate into two parallel fibers running for several millimeters inopposite direction. They make single synaptic contact with a large number of Purkinje cell
dendrites in series. Climbing fibers arise from the inferior olivary nucleus (do not confuse with
the superior olivary nucleus !!!!). These fibers end in an extensive arborisation and are literally
climbing over Purkinje cell dendrites making a large number of synaptic contacts. Synaptic
signals of a single climbing fiber hence exert a strong influence on the membrane potential of a
Purkinje cell. Climbing fibers are thought to send out “correcting signals” in the case of sensory-
motor mismatch.
Chemical senses
The task of a chemoreceptor cell is to signal the nervous system a change in its chemical environment.
Thereby it often acts as a warning system. While gustatory receptors (sense of taste) typically
respond to dissolved molecules olfactory receptors (sense of smell) detect airborne molecules.
Usually both systems closely co-operate. Since taste is 20.000 times less sensitive than smell it is
normally impossible to sense pure taste without overlying smell.
Olfaction
Olfactory cells are located inside the nasal cavity. These cavities are called turbinates and are covered
by the olfactory epithelium, which is approximately 5 cm2 in area in humans. 7- 10 different primary
odorant classes can be distinguished: flowery, fouly, etheric, musk-like, stinging, sweaty, mint-like,
and camphor-like.
The olfactory epithelium is covered by a thin layer of protecting mucus that is produced in mucus
glands. Besides olfactory cells there is a population of basal cells allowing for constant self renewal
of olfactory cells that have only a short life span (maximally two weeks). Olfactory receptors are
primary sensory cells with several long membrane extensions at their tip, called cilia. Receptor
molecules are confined to the cilia.
Olfactory transduction
A relatively large family of genes that are selectively expressed in olfactory cells encode for about
1000 different odorant receptor molecules (making as much as 5% of all our genes). However, only
about 350 of these genes encode for a functional protein. Odorant receptors are seven
transmembrane domain proteins that are coupled with G-proteins (similar as e.g. rhodopsin or
mAchR). Binding of the appropriate odorant causes dissociation of the G-protein complex, beingfollowed by the activation of adenylyl cyclase. The ensuing increase in cAMP level evokes the
opening of a CNG-gated ion channel that has a high Ca
2+
conductance. The calcium influx leads
to a membrane depolarization of the receptor cells. Furthermore, calcium opens chloride channels.
Due to a low chloride concentration in the mucus, chloride flows outward, generating further
membrane depolarization and hence a strong amplification of the odorant signal is attained.
The olfactory signal is rapidly terminated (fast adaptation), since cAMP blocks further G-protein
activation (feedback inhibition). Furthermore, cAMP is rapidly degraded by a phosphodiesterase.
The combinatorial code
The obvious discrepancy between the huge number of odorants that can be discriminated
physiologically and the limited number of odorant receptors available can be explained by the
combinatorial code which is used for odorant identification. Each odorant receptor selectively binds
to a certain chemical group within an odorant molecule. Such a chemical group normally will not
be unique to one odorant molecule but will be shared by many others. Specific odorant identification
is performed by a population of receptor cells that altogether recognize the various chemical groups
residing in one odorant (chemical pattern). This combinatorial code enormously extends the number
of odorants that can be identified by the 1000 different receptor cells.
The olfactory pathway
Axons of olfactory receptor cells terminate in the olfactory bulb of the forebrain. There is an
enormous convergency of about one thousand receptor cells - that all possess the same odorant
receptor molecules- terminating in a cluster of synapses, called glomerulus. Each of the target cells
(mitral cells) sends a highly branched dendrite into one of the glomeruli, and thus receives
information selectively from one class of odorant receptor cells. The axons of mitral cells
collectively form the olfactory tract. This tract splits into three major pathways leading to the
thalamus, the amygdala and the hypothalamus.
Taste
Though our subjective experience is, that there is a large spectrum of tastes, these sensations seem
to be combinations of only five basic qualities:
• _sweet (meaning : food, calories), attractive
• _salty (meaning: salts for maintaining mineral and water balance), attractive• _sour (meaning: potentially dangerous), warning
• _bitter (many toxic substances taste bitter), warning
• _umami = taste of glutamate, attractive
In most vertebrates taste receptors are found on the tongue. At the cellular level taste receptor cells
are grouped together in taste buds. These are arranged on papillae (fungiform, foliate,
circumavallate). Taste buds lie in a tissue cavity with a pore on top.
They consist of receptor cells surrounded by supporting cells. A taste bud contains more than 25
receptor cells. Taste receptor cells are secondary sensory cells with short membrane extensions,
called microvilli, at their upper surface. Each taste cell is innervated at its base by the peripheral
branches of the axons of primary sensory neurons. Each sensory fiber branches many times,
innervating several taste cells within numerous taste buds. The release of neurotransmitter from taste
cells onto the sensory fibers induces action potentials in the fibers and the transmission of signals to
the sensory cell body. Though each taste receptor cell is most effectively stimulated by one type of
stimulus, it also responds to others. Taste information appears to be encoded by means of
interactions between many elements of different specificities.
Like olfactory receptors taste receptors have a short life span of about one week and they are
constantly replaced.
Signal Transduction
How do molecules interact with membranes to produce distinct tastes?
Salty stimuli, such as sodium chloride, readily dissociate in water and the sodium ions passively
diffuse through specialized sodium channels, thus depolarizing the cells. These sodium channels are
distinctive, since they are not voltage-gated but can be blocked by the drug amiloride. Sour stimuli,
which are characterized by an excess of protons, act through so-called PKD2-channels (polycystic
kidney disease channels).
Bitter and sweet stimuli act through G-protein coupled receptor molecules.
Free nerve endings of the trigeminal nerve respond to very strong stimuli, e.g. stingent (nasal-
trigeminal), spicy-hot (oral-trigeminal) pepper.
Taste cells use ATP as neurotransmitter, that is not released by exocytosis of synaptic vesicles but
via half channels of gap junctions.
The gustatory pathway
• _a branch of the facial nerve-(7th cranial nerve) – contacts the anterior two thirds of the tongue• _glossopharyngeal nerve (9th cranial nerve, also touch and temperature sensitivity) and vagus
nerve (10th) innervate the posterior third and the pharynx
• _they carry the information to the Nucleus solitarius in the brainstem (medulla oblongata) and
from there
• _either to the thalamus and temporal cortex (close to the somatosensory fields of the face) or as
a second branch to the amygdala and hypothalamus (limbic system, conveying emotional
aspects of taste).