Hippocampal Functioning and the Results of Lesions to the
Hippocampal Formation 
by Karen Wilson

The hippocampus has been identified as a key area in the
brain for the function of learning and memory.  There has
been much research done on the functioning of the
hippocampus, much of which has focused on the role of the
hippocampus in learning and memory.  Lesions to the
hippocampus can produce severe memory deficits as well as
deficits in other areas of behavior.  This paper seeks to
examine the effects of lesions to the hippocampus.  The
studies to be reviewed will be primarily on human
subjects.  

Anatomy and function of the hippocampal formation

The hippocampus lies underneath the cerebral cortex in
the temporal lobes and is located between the thalamus
and the cerebral cortex (Kalat, 1992).  It is located
posterior to and partially overlaps with the amygdala
(linked reference).
The hippocampus along with the entorhinal cortex, the dentate
gyrus, and the subicular complex make up the hippocampal
formation (Carlson, 1994).  Along with the amygdala, the
hippocampus is part of the limbic system. 
The hippocampus contains two major axon tracts, the
fimbria and the fornix, which link to the hypothalamus
and other subcortical structures (Kalat, 1992).  The
entorhinal cortex serves as the major input and output to
neocortical areas.  The major inputs come from the
surrounding neocortex of the temporal lobe and the septal
area.  Most inputs join with the fornix, which connects
with the septal region, preoptic nuclei, cingulate gyrus,
the mammillary bodies and the hypothalamus (Grossman,
1973).  The entorhinal cortex receives inputs, sends
impulses through the axons of the perforant path to the
granule cells of the dentate gyrus, which then send
impulses to the CA3 region where synapses are made with
pyramidal cells in CA3 (Carlson, 1994).  From CA3,
impulses can take two different routes.  Some axons make
synapse with region CA1, which also receives inputs from
the contralateral hippocampus, while others make synapse
with the septum and mammillary bodies by way of the
fornix (Carlson, 1994). 
In humans, the hippocampus has been found to be primarily
involved in learning and memory.  Long term potentiation
(LTP) seems to be the primary mechanism by which the
hippocampus is involved in learning and memory. 
Long-term potentiation is characterized by a "long-term
excitability of a neuron to a particular synaptic input
caused by repeated high frequency activity of that input"
(Carlson, 1994).  Within the hippocampal formation, when
axons from the entorhinal cortex that are synapsing with
the dentate gyrus become intensely stimulated, there is a
long-term increase in the magnitude of the excitatory
post-synaptic potentials in the postsynaptic cells, thus
long-term potentiation occurs (Carlson, 1994). 
People with lesions to the hippocampus often exhibit
anterograde amnesia, which is amnesia for events that
occur after a trauma to the brain.  Patients with such
lesions are able to learn new tasks and are able to
recognize new stimuli, but are unable to say that they
have learned anything new (Carlson, 1994).  It seems that
patients with anterograde amnesia are unable to make
complex relations between stimuli.  Carlson (1994) states
that this has led researchers to believe that lesions to
the hippocampus can cause a failure to make complex
associations between stimuli.  This suggests that the
hippocampus is involved in making complex relations
between stimuli.  Carlson (1994) reports that many
studies have been done that suggest that the hippocampus
is involved in assisting animals in making relations
among stimuli, but not so much in remembering individual
stimuli.  Carlson (1994) hypothesizes that the original
role of the hippocampus may have been to help animals
orient themselves in different locations, but that the
role has developed into learning complex relationships
between stimuli.  

The effects of lesions to the hippocampus in human
subjects 
Many experiments have been performed to investigate the
effects of lesions to the hippocampus.  Research has been
done on both human and non-human subjects.  This paper
will emphasize research done on human subjects. 
The research on the effects of hippocampal lesions in
humans has focused primarily on memory deficits that
occur with damage to the hippocampus. The most severe
impairments seem to occur when damage is bilateral.  When
damage is unilateral, patients seem to have much milder
memory impairments (Grossman, 1973).  One of the most
famous subjects to be studied with hippocampal lesions is
patient H.M.  H.M. received bilateral resection of the
medial temporal lobe to treat severe epileptic seizures
that could not be controlled by medication (Carlson,
1994; Rempel-Clower,1996).  It was found that H.M.
suffered from anterograde amnesia, meaning that he was
unable to remember events that occurred after the
surgery.  H.M. and other patients with similar brain
damage are able to learn new tasks, but are unable or
have great difficulty learning new facts and events that
occur after brain damage (Kalat, 1992).  H.M. also
suffered slight retrograde amnesia, which is a loss of
memory for events that occurred before damage to the
brain.  Although H.M. can learn new tasks he does not
remember learning the tasks (Kalat, 1992). 
There have been many case studies done on patients such
as H.M.  A study done by Rempel-Clower et al (1996)
compared the memory deficits with lesions to the
hippocampus of three individuals.  The three patients
studied were males who had been studied from the start of
their amnesia to their deaths.  Results from memory tests
done while the patients were alive were compared with
postmortem analysis of brain tissue in each of the
subjects.  Each of the three subjects had severe
anterograde amnesia and also showed some retrograde
amnesia as well.  The severity of the amnesia differed
slightly among the subjects.  The more damage that was
found in the hippocampus, the more severe the memory
deficits. 
The subjects in this study were given the Wechsler Adult
Intelligence Scale-Revised (WAIS-R) and the Wechsler
Memory Scale-Revised (WMS-R).  Results of these tests
indicated that the subjects had deficits in learning new
material, specifically on tests of word recognition and
recall.  The memory deficits that the patients exhibited
occurred independently of any other cognitive deficits
(Rempel-Clower et al, 1996). 
Each of the three subjects exhibited bilateral damage to
the hippocampal formation and minimal damage to other
areas, with the extent of the damage differing among the
patients. The more extensive the damage the more memory
deficits the patients exhibited.  All subjects showed
damage to the CA1 field of the hippocampus.  One subject
had damage only to the CA1 area, while the other two
subjects showed more extensive damage throughout the
hippocampal formation.   
The findings of the study by Rempel-Clower et al (1996)
correspond to the findings of other studies.  In a study
by Bechara et al (1995), patients with bilateral damage
to the hippocampus showed a failure to retain facts, but
were able to acquire conditioning to stimuli.  This also
correlates with the findings from patient H.M., who was
able to learn new tasks, but was unable to recall facts
or recognize that he had learned new the tasks. 

The effects of lesions to the hippocampus in non-human
subjects 
Because studies with human subjects are often quite
difficult, numerous studies with non-human subjects have
been completed to test the effects of lesions to the
hippocampus in an attempt to better understand
hippocampal functioning in humans.  Mumby et al (1995)
used a variety of object-memory tests to examine the
memory deficits in rats following lesions to the
hippocampus.  Most of the deficits found were in relation
to how fast the rats mastered certain tasks.  Mumby et al
(1995) found that the lesioned rats were able to reach
the same performance levels as the control rats.  They
hypothesize that the lesions did not cause deficits in
normal task performance, but that the lesions caused
deficits in the rats' ability to form strategies for
solving the tasks.  Mumby et al (1995) report that these
findings are consistent with the findings of other
researchers studying hippocampal lesions in monkeys.  The
rats also showed deficits in an object-discrimination
task that agreed with the results of previous studies
with monkeys.   
The hippocampus is a very complex structure seemingly
involved in learning and memory.  The hippocampus seems
to be primarily involved in the learning of complex
associations between stimuli.  People with lesions to the
hippocampus often have anterograde amnesia.  This
prevents them from remembering events that happened after
brain damage occurred.  These patients are able to learn
new tasks, but are unable to learn relationships between
stimuli and are unable to remember that they learned the
new tasks.   This has been a brief review of the
functioning of the hippocampus and there is still much to
learn about the hippocampus and its functioning in
humans. 

  
References

Carlson, N.R.  Physiology of Behavior, 5th edition. 
Boston:  Allyn and Bacon, 1994. 
Bechara, A., et al (1995).  Double dissociation of
conditioning and declarative knowledge relative to the
amygdala and hippocampus in humans.  Science, vol. 269,
1115-1118. 
Grossman, S.P.  Essentials of Physiological Psychology. 
New York:  John Wiley & Sons, Inc., 1973. 
Kalat, J.W.  Biological Psychology, 4th edition.  Pacific
Grove, Ca.:  Brooks/Cole Publishing Company. 
Mumby, D.G., et al (1995).  Memory deficits following
lesions of the hippocampus or amygdala in rat: 
assessment by an object-memory test battery. 
Psychobiology, 23 (1), 26-36. 
Rempel-Clower, N., et al (1996).  Three cases of enduring
memory impairment after bilateral damage to the
hippocampal formation.  The Journal of Neuroscience, 16
(16), 5233-5255. 
http://sol.med.jhu.edu/manual/protocol/amyg.html

Copyright © 1997, Dr. John M. Morgan, All rights reserved - This page last edited March 17, 1997
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