Visual Perceptual Memory
Group Project #1
Psychobiology 325
March 9, 2001

Debra Pizzuto
Michael Fry
Shaw Gillespie


Introduction

     The following pieces explore the phenomenon of long term visual 
perceptual memory, touching on cerebral relationships, synaptic changes, 
and physiological differences in the visually impaired. The first piece 
covers cerebral pathways relating to visual perceptual memory and 
learning, and functions of these pathways. The second portion explores 
the locations and mechanisms of synaptic change that facilitate visual 
associative memory.  The final portion deals with the genetic 
characteristics of a rare visual disorder at the photoreceptor level of 
the retina.  


Cerebral Relationships of Visual Perceptual Learning and Memory 
by: Debra Pizzuto 
 
     The act of conscious perception of a sensory impression and the 
content of perception with meaning and association are two factors of 
perception. Learning involves recognition. Study of learning involves 
how to recognize stimuli, changes and variations of the familiar. 
Physiologically, visual perception involves changes in the structure of 
neuronal synapses resulting  
from past experience in the visual environment. Donald Hebb 
hypothesized in 1949, if a synapse is repeatedly active when a 
postsynaptic neuron fires, changes take place in the structure that 
will change it. This change is the proposed mechanism of long term 
potentiation (LTP) phenomenon involved in strengthening of synaptic 
connections within memory networks. (LTP) is the enduring increase of 
synaptic efficiency following the repeated activation of presynaptic 
fibers. This form of postsynaptic excitatory facilitation was 
discovered in synaptic elements of granular cell dendrites in the 
dendrite gyrus which receive inputs from the entorinal cortex via 
perforant path (Will,140). The process seems at least theoretically to 
physically change the structure of neural systems in the brain when 
learning occurs.  

     Phenominalogy mechanisms extensively reviewed by Swanson et 
al(1982), Voronin (1983), and Eccles (1983) in Buser's Cerebral 
Correlates of Conscious Experience, distinguishes three elements of 
LTP: long duration, lasting enhancement of synaptic efficiency produced 
by short high frequency stimulus that mimic bursts of activity 
occurring in hippocampal neurons spontaineously. LTP also requires a 
number of coactive convergent synapses to be set into an active state. 
There is much evidence that synapse remodeling occurs as a result of 
specific learning experiences in adults, early visual cues and one 
trial avoidance learning.

     Additionally, studies based on experimental evidence from 
depriving in neonates or exposure to enriched environment in early life 
and adulthood (Rosenzweig & Bennet, 1976) propose that relatively 
permanent fixation of acquired information is the result of a long 
lasting change in some synaptic parameter with resulting formation of 
neural pathways. Behavioral studies  
compare with numerous studies finding patients with inferotemporal 
cortex lesions made numerous errors during initial learning of visual 
discriminations, as well as recall of previously learned discrimination 
(Merigan & Maunsell, 1993). 
Persistent synaptic modifications in neural networks seem to be the 
basis for information storage. Therefore, memories are 
multidimensional. Synaptic reorganization occurs in multiple relays in 
relevant networks throughout the brain.  

     Without excitation from relevant stimuli (inactive memory), the 
network defined by the activity pattern along the connective structure, 
is potentially maintained by permanent connection points within the 
network (Bloch& Laroche, 1984). Bloch and Laroche examined the 
development of LTP in learning proposing that the change is assumed to 
occur during the phase of information processing, generated by 
perseverative activation triggered in neural networks by incoming 
information.  

     Perseverative processes may play a role in storage and retrieval 
of information as their studies further indicate. In these studies, MRF 
stimulation was delivered 10 seconds after each high frequency train to 
perforant path fibers. Experimental findings parallel the behavioral 
data in classical conditioning. Behavioral studies provide strong 
evidence that a low intensity post trial MRF stimulation facilitates 
learning in a variety of experimental situations, including active 
avoidance (Bloch et al, 1970), extinction of bar pressing or maze 
learning (Deweer,1976). 

     Two limbic circuits mediate neural pathways, with sensory input 
from the frontal cortex in the hippocampal system. According to 
Kornhuber's theory, hippocampal formation response to sensory stimulus 
seems to have predictive value rather than a specific behavior 
response. First the Papez loop: hippocampus, subiculim, mammillary 
body, anterior thalamic nucleus, cingulate gyrus, and hippocampus. The 
other circuit leads from the association cortices to the hippocampus 
via the cingulate gyrus and the mediodorsal thalamus to the prefrontal 
lobe (Buser, 1978). The inputs from the frontal, to the (sensory) 
temporal and parietal association areas send to the hippocampus via the 
cingulate gyrus. These areas identify memory and establish new circuits 
in learning. Lesions to the temporal cortex cause difficulty with form 
discrimination (agnosia). The output from the hippocamus (primordial 
cells) is via the mediodorsal thalamus to the frontal lobe. This area 
is involved with the perception of objects location in space (Buser, 
1978). 

      Most complicated processes of molecular biology are involved in 
visual perception. Researchers find difficulty drawing theoretical 
conclusions from data examined. Damage to the visual system at any 
level can effect profoundly the adequacy of perception and the 
efficiency of its accomplishment. When higher parts of the visual 
system are destroyed, the production of visual consciousness ceases to 
operate. Researchers indicate that cerebral relationships of neural 
networks consisting in multilevel divisions seem to contribute to 
visual perceptions leading to learning and LTM. 
 
References:
 
Buser, P. & Rougeul Buser, A. (1978). Cerebral Correlates of Conscious 
Experience. Netherlands: Elsevier/North Holland Biomedical Press 
 
Carlson, N. R. (2001). Physiology of Behavior. Needham Heights MA: 
Allyn and Bacon 
 
Dimond, S. J. (1980). Neuropsychology. Boston, MA: Butterworth  
Publishersinc. 
 
Tsukada, Y. & Agranoff, B. (1984). Neurobiological Basis of Learning 
and Memory. New York: John Wiley & Sons 
 
Will, B.E (1984). Brain Plasticity, Learning, and Memory. New York: 
Plenum Press



Synaptic Mechanisms of Long Term Visual Perceptual Memory
by Shaw Gillespie

     It is currently common consensus among researchers that perceptual 
learning (recognition of a particular stimulus or categories of 
stimuli) is generally the domain of regions of the appropriate sensory 
association cortex (Carlson, 1997). Here we will narrow the scope, 
looking only at visual perceptual memory and evidence revealing the 
locations and mechanisms that make visual perception and recollection 
possible. 

Locations
     While visual short term memory seems to involve areas of the 
prefrontal cortex (Quintana and Fuster, 1999; Blumhardt, 1999), 
evidence supports the idea that cells in the temporal / temporal 
occipital region are highly specialized, responding to an aggregate of 
color, form, texture, and shape data from the extrastriate cortex. Long 
term visual perceptual memory involves changes at the synaptic level in 
these cells in the inferior temporal cortex (Tanaka, 1993). However, 
Biederman et. al. (1995) has found evidence that indicates that the 
anterior region of the inferior temporal cortex may not be involved in 
perceptual memory or recall.

    Likely, the synaptic changes in the inferior temporal region 
responsible for visual perception of complex stimuli involve the 
strengthening of various synapses through a process such as long term 
potentiation (LTP). There is evidence to implicate NMDA receptors as 
contributing to LTP in the mammalian visual cortex (Seki, Kudoh & 
Shibuki, 1999). Additionally, Niu et. al. (1999) found that the 
presence of NMDA antagonists inhibited synaptic strengthening by long 
term potentiation in rat hippocampi. Given all this, it seems likely 
that LTP plays some role in the formation of new neural circuits in the 
visual cortex, and it is possible that LTP contributes to the synaptic 
changes responsible for perception of complex visual stimuli by cells 
in the inferior temporal cortex.

Mechanisms
     The increase in synaptic strength due to LTP may be the result of 
several different types of changes in the postsynaptic, presynaptic, or 
both pre and postsynaptic cells. There is evidence to support all of 
these possibilities. Additionally, there is evidence that links changes 
in presynaptic neurons to the initial postsynaptic changes that occur 
due to the influx of calcium though NMDA controlled ion channels. 

     Postsynaptic changes include increased number of postsynaptic 
receptors, increased communication between the postsynaptic spine and 
the rest of the cell, and increased ability of postsynaptic receptors 
to affect cell membrane permeability. Presynaptic changes that 
strengthen the synapse involve an increased release of 
neurotransmitter. Synaptic changes that involve both the pre and 
postsynaptic neurons include the formation of new synapses.

     Evidence pointing to postsynaptic change contributing to the 
synaptic strengthening seen during LTP has been accumulating rapidly. 
NMDA mediated LTP has been shown to increase the number of AMPA 
receptors(Liao, Hessler, and Malinow, 1995), which strengthen the 
synapse by virtue of being able to more effectively produce excitatory 
postsynaptic potentials, and to decrease the number of NMDA receptor 
sites(Segal & Andersen, 2000). These changes take place through action 
of...

     Increased communication between synapses has been seen to occur 
through the action of what are termed perforated synapses, and Buchs 
and Muller (1996) have observed that LTP has lead to the formation of 
perforated synapses in targeted dendritic spines. Perforated synapse 
formation can involve both small and large scale shape changes. These 
changes involve bringing more of the spine's membrane surface closer to 
the presynaptic bouton, so that it can form a larger active site or a 
greater number of active sites that facilitate the triggering of 
postsynaptic potentials. Small scale shape changes to the spine can 
take place without the addition or removal of new membrane material due 
to the membrane fluidity (Segal and Andersen, 2000). However, large 
scale changes require the addition of new membrane material through the 
action of lipid vesicles and protein synthesis. The conversion of ATP 
to cyclic AMP (triggered by calcium influx) within the postsynaptic 
spine triggers the phosphorylation of various proteins within the cell. 
Sanchez et. al. (1999) found evidence linking the phosphorylation of 
the microtubule associated protein 2 family of proteins to large 
changes in cell structure and plasticity.
 
     Another type of change involving the postsynaptic neuron involves 
increased communication between the dendritic spine and the rest of the 
postsynaptic neuron. Following long term potentiation, the neck of an 
affected dendritic spine becomes thicker to facilitate better 
intracellular chemical communication with the rest of the cell. These 
structural changes are thought to be accomplished through 
phosphorylizing action of type calcium calmodulin kinase on various 
MAP2 type proteins that can carry new membrane material to the spine 
from the rest of the neuron(Sanchez et. al., 1999). 
     
     Changes in presynaptic neuron such as the spouting of new terminal 
boutons are thought to be the result of signaling by the postsynaptic 
cell by way of nitric oxide (Carlson, 1997). Production of nitric oxide 
is mediated by nitric oxide synthase activated by events resulting from 
the entry of calcium into cell during LTP. Nitric oxide gas is highly 
soluble and can diffuse across a wide area in a relatively short time, 
providing a convenient messenger to the presynaptic cell. In the 
presynaptic cell, there is evidence to suggest that nitric oxide 
triggers a heightened amount of cyclic GMP which, in turn, leads to a 
heightened amount of neurotransmitter released when the presynaptic 
bouton fires (Haley, Wilcox and Chapman, 1992; Mize and Lo, 2000).

     Overall, it seems that the process of LTP does not involve a 
single change, but rather a series of changes, or chain reaction, that 
leads to alteration of both the pre and postsynaptic cell. 
Theoretically, these changes refine associative neural pathways in the 
inferior temporal cortex that contribute to the perception and 
recognition of visual stimuli.

References:

Blumhardt, L. Characterising brain activity associated with short term 
memory processes. Electroencephalography and Clinical Neurophysiology, 
1997, 103, 48.

Biederman, I., Gerhardstein, P., Cooper, E., and Nelson, C. High level 
object recognition without an inferior temporal lobe. Neuropsychologia, 
1995, 3, 271 to 281.

Buchs, P., and Muller, D. Induction of long term potentiation is 
associated with major ultrastructural changes of activated synapses. 
Proceedings of the National Academy of Sciences, USA, 1996, 93, 8040 to 
8045.

Carlson, N. Physiology of Behavior. Massachusetts: Allyn and Bacon, 
1998.

Haley, J., Wilcox, G., and Chapman, P. The role of nitric oxide in 
hippocampal long term potentiation. Neuron, 1992, 8, 211 to 216.

Liao, D., Hessler, N., and Malinow, R. Activation of postsynaptically 
silent synapses during pairing induced LTP in CA1 region of hippocampal 
slice. Nature, 1995, 375, 400 to 404.

Mize, R.,  and Lo, F. Nitric oxide, impulse activity, and neurotrophins 
in visual system development. Brain Research, 2000, 886, 15 to 32.

Niu, Y., Xiao, M., Karpefors, M., Wigstrom, H. Potentiation and 
depression following stimulus interruption in young rat hippocampi. 
NeuroReport, 1999, 10, 919 to 923.

Segal, M., and Andersen, P. Dendritic spines shaped by synaptic 
activity. Current Opinion in Neurobiology, 2000, 10, 582 to 586.

Sanchez, C., Diaz Nido, J., Avila, J. Phosphorylation of microtubule 
associated protein 2 and its relevance for the regulation of the 
neuronal cytoskeleton function. Progress in Neurobiology, 2000, 61, 133 
to 168.
 
Seki, K., Kudoh, M., and Shibuki, K. Long term potentiation of calcium 
signal in the rat auditory cortex. Neuroscience Research, 1999, 34, 187 
to 197.

Tanaka, K. Neuronal mechanisms of object recognition. Science, 1993, 
262, 685 to 688.

Quintana, J., Fuster, J. From perception to action: Temporal 
integrative functinos of prefrontal and parietal neurons. Cerebral 
Cortex, 1999, 9, 213 to 221.


The Genetic Characteristics of Blue Cone Monochromacy
By Mike Fry

	Imagine a world void of color, a world without the richness of 
reds or the vibrancy of yellows.  Such an existence is a reality for a 
small fraction of the overall population.  This begs the question as to 
where these people lead less fulfilling lives than those who can 
experience the kaleidoscope of hues that paint the imagination.  
Perhaps, one could argue, there are experiences that will never be had 
but overall achromats, those individuals who have no cone cell 
photoreceptors, and monochromats, those people with only one set of 
functional cone cell photoreceptors, have proven to live fruitful, 
happy lives.  There is some speculation as to whether monochromats can 
decipher color with one set of cones and a full complement of rods 
cells.  Empirical test have illustrated that yellow can easily be 
identified on a blue background and vice versa.  Blue Cone Monochromats 
(BCM) have reported that they do actually experience color, though may 
be a perceptual illusion.  Some people with BCM have reported being 
able to distinguish among the seven colors of the rainbow and are able 
to pass simple color test
Background
	In the back of the eye is a thin sheet of film like material that 
is directly connected to the brain via the optic verve called the 
retina.  The retina consists of seven layers of specific cells that are 
responsible for relaying information gathered from the photoreceptors 
along the appropriate path to the various areas of the brain.  Perhaps 
due to an evolutionary fluke or possible because of the extreme 
sensitivity of these highly specialized cells, photoreceptor cells 
constitute the inner most layer of the retina.  There are two distinct 
types of photoreceptors called cones and rods.  Photoreceptors primary 
function is to gather and start the initial processing of light that 
enters through the pupil.  
	On a cellular level, rods have a large receptive field and lower 
convergence to magno ganglion cells.  They are located more densely at 
the peripheral regions of the retina becoming sparse towards the 
macular region (center portion of the retina).  Rod cells are highly 
sensitive to light and movement but lack the ability to discriminate 
fine detail or color.  They are largely responsible for scotopic, or 
night vision, and as such they are specialized at gathering information 
about movement, size, and shape of objects, however they have poor 
resolution, an as such cannot distinguish color or detail.
	Conversely, cones are densely packed in the macular region 
becoming less dense in the peripheral areas.  They have a much smaller 
receptive field and significantly higher convergence to parvo ganglion 
cells.  It takes considerably more stimulation to cause a cone to 
increase its random firing.  They are wavelength sensitive and have the 
ability to distinguished fine details.  There are three types of cone 
cells in the retina, each defined by the color of pigment it contains 
corresponding to the wave length frequency they are most sensitive too.  
Cones are commonly categorized as blue (or short wavelength), green (or 
medium wave length), or red (long wave length).  It is the mixing and 
matching of the input from the combinations of these cells that allows 
for normal color vision.  In BCM cone cells develop normally, but due 
to a genetic defect the body is unable to produce the red and green 
Opsin proteins necessary to fill the cone cells with their appropriate 
pigment.  Thus people with BCM have a complete complement of rod cells 
and theoretically the appropriate amount of cone cells, but due to a 
genetic defect they only have an effective class of short wave length 
cones.
Blue Cone Monochromacy 
	Studies have concluded that there are very few if any blue cones 
located in the fovea, a cone rich portion of the retina directly behind 
the pupil, which is responsible for central vision.  Consequently those 
people affected by BCM exhibit symptoms of poor central visual acuity, 
ranging from 20/50 to 20/300, poor color discrimination, early onset of 
nystagmus (shaky eyes), varying degrees of myopia (near sightedness) 
and hypermetropia far sightedness), and photophobia (aversion to bright 
light).  People with BCM have almost normal retinal appearance.  Given 
that fact coupled with the rarity of occurrence makes dig gnosis a 
difficult process.  Often time's people who do have BCM will be wrongly 
diagnosed as hav9ing some other type of retinal disorders, such as 
Retina Pigmatosea.  A color test measuring wavelength sensitivity while 
controlling for light intensity is the most effective means of 
diagnosing BCM.  In occasional cases of BCM people will report 
progressive deterioration of central vision.
	BCM is an extremely rare X-linked recessive retinal disorder, 
occurring in the United States population in an estimated onep3erson 
out of every hundred thousand.  Genes on the X chromosome provide the 
instructions, which manufacture the proteins necessary for the 
production of the red and green Opsin.  Research has implicated linkage 
of BCM to 2 DNA markers (DXS15 and DXS52) that map in the Xq28 (on the 
lower arm of the X chromosome) region.  
	Females usually never display phenotypic symptoms of BCM.  The X 
chromosome is involved with determining a child's gender.  Normal males 
have a genotype of (X, Y) and normal females have a genotype of (X, X).  
A person who has BCM has a defect on a single X chromosome that 
prevents the formation of red and green pigment for cone cells.  A 
female who carries an effectived X chromosomes also always dose not 
show symptoms of BCM, because she also has a normal X chromosome that 
"protects" her form the defect.  X I-inactivation, which is the random 
inactivation of either maternal X or a paternal X chromosome during the 
32 cell stage of pre-embryonic development usually ensures that a 
suitable amount of normal X chromosome will be activated to allow her 
to have a fairly normal collection of red and green cone cells.  These 
normal red and green cone cells accompanied with her blue cone cells 
should allow her to have close to, if not completely normal, color 
vision.  A woman could possibly show signs of BCM if she inherits a 
defective X that is unable to adequately "protect" her from the 
deficiency of cone pigment caused by the abnormal genes on her other X 
chromosome.  
	A male, on the other hand, has only one X chromosome so any 
defect on that chromosome will be phenotypicaly expressed since he 
lacks a second X chromosome to mask the faulty genes expression.  As a 
result, if a male has the BCM defect on his X Chromosome, no red or 
green pigment is formed and he will be affected by BCM.
Inheritance
	A woman who is a carrier of BCM, which means that she has a 
defective X chromosome but dose not display phenotypic symptoms, has a 
50% chance of producing a gamete with an abnormal X chromosome, 
according to the Law of Random Alignment.  Therefore, when the mother 
is a carrier of BCM and the father is unaffected, there is a 50% chance 
that any pregnancy, which results in a daughter, will produce a 
carrier.  For any pregnancy that results in a son, there is a 50% 
chance that the child will have BCM.  Likewise, there is a %)% chance 
of her birthing an unaffected offspring.
	If a male affected with BCM has children with a normal female, 
then all of the children will receive a normal maternal X chromosome.  
All female offspring will receive the fathers X-chromosome coding for 
BCM and thus will be carriers.  All males will receive an unaffected Y 
chromosome and a normal maternal X chromosome and thus be completely 
unaffected.
Causes of BCM
	Deletions, rearrangements, and point mutations in the red and 
green pigment genes have been implicated in causing BCM.  One study 
reported to the OMIM web page stated that nine out of ten families 
studied showed deletions in the gene encoding the red-sensitive photo 
pigment and/or in the region upstream of the red pigment gene which 
contains that locus control region and other regulatory sequences.  In 
the same nine families the red pigment gene showed a range of deletions 
from the loss of a single exon (the DNA base sequence of a gene that 
encode and amino acid) to loss of the complete red pigment-producing 
gene.  In the other family, there was a loss of the complete green 
producing pigment gene.  Another study reported that the alterations to 
the chromosome fell into two classes.  One class arose from the wild 
type by a two-step pathway consisting of unequal homologous 
recombination and point mutation.  The second class arose by 
nonhomologuous deletion of genomic DNA adjacent to the red and green 
pigment gene cluster.  Apparently the research supports the existence 
of multiple one and two-step mutational pathways to BCM.  In a more 
recent study it was reported that out of 24 subjects there where eight 
genotypes found that would be predicted to eliminate the function of 
the red green pigment.  Thus, BCM could be caused by the absence of a 
gene producing red or green cone cell pigment, or the deletion of an 
exon on one of those genes, or by the damaging of a locus region that 
controls the production of those pigment.
Options  
	Regional localization of the locus for BCM has the potential to 
improve carrier detection and to provide antenatal (early cellular 
detection_ diagnosis in families at risk for the disease.  If a women 
suspects that she may be a carrier of BCM because a sibling, father, or 
grandfather has the disorder, she can contact a genetics counselor who 
can determine through DNA analysis of a blood sample if she is a 
carrier.  I a woman happens to be a carrier pre-natal testing such as 
CAVS or amniocentesis can accurately determine if the child will be 
affected by 
BCM.  Despite the rarity of BCM and Achromatopsia and Internet based 
network has been formed by a woman whom is a complete Achromat (no 
functioning cone cells) to allow those people affected to correspond 
with one another.  The network is also open to health care provider and 
scientist interested in learning more about these types of retinal 
disorders.  For more information visit www.acromatopsia.org


References

1.	Online Mendeline Inheritance in Man, OMIM. Johns Hopkins 
University, Baltimore, MD.  MIM Number (303700): (10/5/98):.  
World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/.
2.	Achromatiopsia Network, 200.  World Wide Web URL: 
http://www.achromat.org/
3.	National Organization for Rare Disorders NORD), 2000.  World 
Wide Web URL:  http://www.rarediseases.org/.


  

Copyright © 2001, Dr. John M. Morgan, All rights reserved - This page last edited March 12, 2001
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