The Historical Development of Evolutionary Theory LIFS 691 Advanced Evolution.
Chapter - I Introductionshodhganga.inflibnet.ac.in/bitstream/10603/40136/6/06_chapter 1.pdf ·...
Transcript of Chapter - I Introductionshodhganga.inflibnet.ac.in/bitstream/10603/40136/6/06_chapter 1.pdf ·...
Chapter - I
Introduction
It is an established fact that one's life
is influenced greatly by p^st experiences. Generally
the term memory is used to refer to the consequences
of past experiences. Foi . any learning to result in
a changed behaviour the learning stimuli will have
to be stored somewhere in the brain. The act of demons-
trating memory is very of.ten a retrieval of stored
information. However/ the nature of the triggers for
memory retrieval from its stored state into performance
are not very well understood. One type of trigger
appears to be an equivalency or at least a similarity
in the biochemical state oif the brain to the state
in which the original learning occured.
Learning that is,i acquired under a specific
condition and later retrie^ved only when the same con-
dition is reestablished is called state dependent
learning (SDL). When SDL occurs/ a behavioural response
learned while the animal is drugged will thereafter
be performed well whenever the animal is again drugged,
but will be performed p cEtorly or not at all during
tests without drug*. Conversely/ a response learned
while undrugged will be adequately performed without
drug and will be poorly performed when the drug is
present. Engrams acquired in one drug state are said
to be dissociated and hence irretrievable in anpther
drug state.
The most convincing demonstration' of state
dependent performance has been provided by the obser-
vations that an organism behaves adaptively is a speci-
fied situation under both normal and abnormal conditions
but the type of behaviour displayed at a moment is
determined by a particular state imposed at that stage.
The first example of state dependent learning was
provided by Lashley (1917) who trained rats in a maze ro- vcv *
after administration of strychlne or caffeine and
found that strych'ine enhanced the rate of acquisition I of the maze habit/ while caffeine resulted in slower
acquisition. In comparision to the control group both
the drug groups took longer to relearn the maze when
tested subsequently without the drug. Girdan and Culler
(1937) and Girden (1942a, b, c; 1947) conditioned
a number of autonomic and muscular responses in dogS/
cats and monkeys injected with crude curare or dihydro-
^ -erythroidine HBR. The conditioned response thus
established could not be subsequently demonstrated
in the undrugged state, but reappeared after the admi-
nistration of the drug^ Case and Funderbank(1947)
reported similar dissociation with physostigmine.
These findings suggest that severe response
decrement can be produced by a difference in the state
of the central nervous system at the time of training
and testing. Some investigators have proposed that
this decrement could be due to changes in the stimulus
as perceived by the subject. Carson (1957) demonstrated
that the rats could acquire a conditioned avoidance
response (CAR) quite rapidly in the period following
ECS but demonstrated no retention when tested several
days later. As distortion in perception of the stimuli
could occur in the period following ECS, this effect
can only be attributed to the difference in the state
of the CNS due to the gradual return of the perturbed
nervous system to a more normal state.
The most convincing evidence against the
stimulus change explanation for dissociation of learning
has been provided in a series of experiments by Overton
(1964). He used the saving method to evaluate the
degree of state dependency and argueid that if learning
in the drugged and non-drugged state is completely
dissociated, it shou-ld be possible to develop different
response tendencies in the two states concurrently
by alternate training trials under the two conditions.
It was found that rats in the experimental group learned
to turn toward one goal box when drugged and opposite
goal box when not drugged. Since the difference in
the amount of training trials was not significants
it is apparent that no transfer of training occured
between the two experimental conditions.
In another investigation by the same investi-
gator/ it was found that not all dissociation phenomena
are the result of some single process such as changes
in arousal level. A set of depressant drugs including
pentobarbital/ phenobarbital, alcohol, urethane and
meprobamate produced a state in which learning was
partly dissociated from learning in the non-drug state.
These substances were approximately equivalent in
their actions and their actions were interchangeable.
Anticholinergic drugs including atropine and scopolamine
were found to produce a state in which learning was
partially dissociated both from the non-drug and de-
pressant drug state. The effects of atropine which
produced this state neither mimicked nor antagonized
the dissociative effects of the depressants. This
study also showed that the amount dissociation of
learning caused by a particular substance may vary
sharply from task to task. Since there is no reason
to believe that the action of a given drug on the
state of various brain regions will vary with the
task, this finding illustrates that involvement of
brain regions in the mediation of learned responses
varies from task to task.
Thus it appears that learning acquired under the influence of a particular drug is generally best
retrieved when tested under the influence of same
drug.. This effect is attributed to the stimulus proper-
ties of the drugs and may occur independent of their
influences on acquisition or memory storage. In recent
years/ it has been proposed that learning might depend
on states induced by endogenous substances. State
dependent influence of endogenous substances have
been observed by a number of investigators (Gray,
1975; Spear/ 1978; Zornetzer, 1978; Izquierdo, 1980;
Riccio and Concannon, 1981; Izquierdo et al. / 1982;
Izquierdo and Dias, 1983). During and after various
forms of training there is a release of central and
peripheral cate'^holamines (Gold and Delanoy, 1981)
brain -endorphin (Izquierdo et al., 1982)/ and possi-
bly pituitary ACTH (Gold and Delanoy/ 1981; Riccio
and Concannon/ 1981). Neuroharaoral and hormonal changes
during test sessions have been much less investigated,
but there are reasons to think that they may be smaller
than those that occur during training. The central
p-endorphine release certainly is smaller during test
sessions (Iz^ierdo et al w 1982) and possibly the
hypersecretion of peripheral catecholamines and ACTH
is also less pronounced during testing^ particularly
if this does not involve the use of footshocks (Gold
and Delanoy/ 1981). Also, the administration of small
doses of epinephrine (E)^ /2-endorphin/ or ACTH prior
to testing counteract the amnesia caused by the same
substances when given after training (izquierdo and
Dias, 1983).
It is, therefore, possible that since the
treatments which affect memory are physiological
stressors/ they have their effect due to an excessive
neuroendocrine response. However, it was general
through that these treatments affect learning and
memory through direct influences on brain processes
underlying the storage or consolidation of recently
acquired information (McGaugh,1966; and HerZ/ 1972),
One of the most intriguing feature of these
treatments is that their impairing and enhancing effects
are t ime dependent. The magni tude of these effects
on memory decreases with a subsequent increase in
the time between training and treatment. However,
this decrement does not necessarily reflect the time
required for memory formation (Gold and McGaugh, 1975).
This view is supported by a number of investigators
who have reported that the temporal gradient of sus-
ceptibility to modification varies with the severity
of a particular treatment (Alpern and McGaugh^ 1968;
Gherkin, 1969; Gold, Macri and McGaugh, 1983; Ma'fi
and Albeftrt/ 1983). The interval after training during
which a treatment can alter retention performance
seems to be an indicant of the treatment's effective-
ness rather than that of a time required for memory
formation.
On the basis of these investigations the
hypothesis of memory modulation (Gold and McGaugh,
1975)/ which focuses attention on conditions under
which memory can be altered/ was formulated. It seems
that some biologically adaptive responses to training
such as alterations in arousal level, autonomic function
or neuro-endocrine activity might be correlated with
memory storage. From this perspective it appears that
memory/ in untreated animals/ might be modulated by
certain endogeneous responses to training (GoId/van
Buskirk and Haycock/ 1977).
The discovery of hormones dates back, to 400B.<^.
STRESSOR
d
ASCENDING RETICULAR ACTIVATING SYSTEM
CORTICAL ASSOCIATION AREAS VIA SENSES
JTOMATIC NERVOUS SYSTEM
ADRENAL MEDULLA
ANTERIOR PITUITARY POSTERIOR PITUITARY
ACTH \f^SOPRESSlN
EPINEPHRINE AND
NOREPINEPHRINE
ADRENAL CORTEX
OTHER GLANDS
JL KIDNEY
^CORTICOIDS
GENERAL -resisTKNCE
OTHER HORMONE AND ELECTROLYTE
CHANGES
CRF = CORTICOTROPIN RELEASING HORMONE ACTH = ADRENOCORTICOTROPIC HORMONE
FIG I A GENERAL OUTLINE OF THE'^M^AJOR STRUCTURES AND THEIR SECRETIONS DURING THE STRE^SS REACTION.
when Hippocampus postulated that health is dependent
on the proper balance .of humors in the body. However/
the historyfof endocrinology, actually begins with
Berthold (1849) who studied the function and mode
of action of the testers in cockerels. He reported
a humoral effect indepen<3ent of any specific neural
control. Since then a -large number of hormones have
been . identified, Hoirmones have extremely diverse
but specific functions which may be limited to a parti-
cular or extended to more/ organs. Their secretion
is triggered off by certain stimuli which tend to
displace the internal, state of homeostasis. The source
ot the stressor may be external or Internal, Generally
the thyroid/ parathyroid; pancreas and posterior
pituitary glands main^aij:t the balance of body. However/
if displacement is more intense/ then a more dramatic
endocrine response-th^. stress reaction - occurs. This
reaction is specific/ dominated by an increase in
specific hormonal secretions of two endocrine glands-
the pituitory and the .^adrenals. These stress related
•r>euro-endocrine responjses are depicted in Figure 1.
Since each learning situation is a stressful
situation in itself/ i•t^is possible that the peripheral
endocrine changes i.e. the release of pituitary and
adrenal hormones, resulting from the training procedure
10
used in various tasks/ modulate memory. Inhibitory
avoidance training is followed by release of adrenaline
from the adrenal medulla, noradrenaline from the sym-
pathetic nerve endings and ACTH from the pituitary
gland (Gold et al., 1981). Various forms of aversive
and nonaversive training are also accompanied by the
depletion of brain catecholamines (Gold and van Buskirk/
1978).
Naka.jima (1975) reported that the effect
of cycloheximide (CXM), a protein synthesis inhibitor^
on retention is due to its influence on certain hormones
(e.g. corticosteroids) and not due ' to inhibition of
protein synthesis inhibition. This fact is supported
by the results of their experiment in which it was
observed that subcutaneous injection of CXW shortly
before training in a passive avoidance task did not
result in amnesia in adrenalectomized rats. Thus it
appears that secretions of the adrenal glands mediate
the CXM produced amnesia. Flexner et al. (1972)
pointed out that vasopressin (VP) , a pituitary hormone^
is also capable of blocking the memory dusruptive
effects of certain amnestic agents. It antagonizes
the memory disruption produced by the protein synthesis
inhibitor, puromycin.
li
Further support for the role of endocrine
changes in memory modulation is provided by' a number
of investigations in which various hormones were found
to facilitate memory when administered in a less intense
dose while higher dose caused amnesia. In an investi-
gation by Gold and van Buskirk (1975)/ rats received
an injection of saline or one of the levels of E.
Retention performance was tested 24 hours later. Animals
that received injections of loWer doses of E had
retention latencies significantly higher than those
of the saline injected controls.' A higher E dose
appeared to produce amnesia in many animals. Similarly
Gold and van Buskirik (1976) found that lower doses of
4norepinephrine {NE) and ACTH enhanced retention after
high footshock while higher doses caused amnesia.
Low doses of VP enhanced retention of an inhibitory
avoidance response..
Thus a number of hormones have been reported
to modulate memory processes when administered peri-
pherally. Of these hormones, the most effective evidence
in this regard has been obtained in studies of the
effects of E on memory.
E is the major active principle of the adrenal :nedulla. Its jecretion level varies as a function
of the general level of stimulation of the nervous
system. Very little or none is secreted under basal
conditions (sleep)/ but even relatively mild activity
such as walking produces a marked secretery activity.
Strong stimuli/ particularly if prolonged/ painful
or emotional, flood the entire organism with E and
NE (Vane, VSolsten^holme and Connor 1960). There is
extensive evidence that peripheral E can' regulate
the mechanism responsible for the storage of new memo-
ries (Gold and Zornetzear, 1983; McGaugh/ 1983; McGaugh
and Gold^ 1986). This view is supported by the demon-
strations that post-training injections of E can enhance
memory for both avoidance (Gold and van Buskirk* 1975/
1976/ 1978a/ 1978b; Gold, Van Buskirk and Haycock/
1977; Izquierdo and DiaS/ 1983 a/b; Introini-Collision
and McGaugh ^ 1986) and appetitive tasks (Sternberg
et al./ 1985), enables classical conditioning to occur
under deep anesthesia (Weinberger, Gold^and Sternberg,
1984; Gold^ Weinberger, and Sternberg, 1985),
retards rapid forgetting seen in juvenile (Gold, Murphy
and Cooley, 1982) and aged (Sternberg, Martinez/ McGaugh
and Gold, 1985) rodents, and enhances the development
of long term potentiation (Gold/ Delanoy and Menin,
1984).
13
The effect of peripherally injected E has been found to be dose
dependent. Memory enhancement is seen at moderate doses and
amnesia observed at high doses (Gold and van Buskirk/ 1975/
1976; Gold, van Buskirk and Haycock, 1977).
Furthermore, it has been found that the effect of E is time dependent-a negative relationship exists between the effectiveness of a dose and increase in the training treatment interval.
The retention impairment effect of post train-
ing E might be a consequence of any of several influ-
ences-a^ an interference with storage mechanisms/b)
state dependency (Izuierdo and Dias/ 1983 a/bj^c)
release of brain p - endrophin (Carrasco et al / Izui-
erdo, 1982/1984) and the consequent establishment
of state-dependency on p -endorphin (Izquierdo and % Dias/ 1985; Izuierdo and NettO/ 1985a/ 1985b). A
Evidence against the first explanation is
available from studies (XzquierdO/ 1984; Introini-
Collison and McGaugh/ 1986) in which good retention
performance is seen after post training E/ if the
animals are also injected with E before the retention
test. Alternatives b and c are not mutually exclusive/
and there is evidence in favour of both. In favour
of alternative (b) i.e. State dependency on E, is
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the finding that the impairment of retention caused
by post training E can be reversed by another injec-
tion of ACTH/ tyraminejor j3 -endorphin given shortly
before the retention test (izquierdo/ 1984); although
E is more effective in reversing E amnesia (Izquierdo
and Dias/ 1983b/ izquierdo/ 1984). in favour of alter-
native (c) -an effect mediated by ^ endorphin are
the findings that novel training experiences are acco-
mpanied by a release of brain yj-endorphin, (Izquiredo
et al./ 1984; Izquierdo^f^Netto, 1985 a) which sets
up a form of state dependency; retention test perfor-
mance can be enhanced by a post training injectiono^
opiate blockers/ including naloxone or naltrexone
(Messing et al., 1979; Izquierdo, 1979/ 1980/ 1984;
Gallagher, 198i; Izquierdo and Dias> 1985; Izquierdo
and Netto, 1985a, 1985b) or by pretest administration
of 0 -endorphin (Izquierdo, 1980, 1984;Izquierdo and
Dias, 1985; Izquierdo and McGaugh, 1985b; Izquierdo
and Netto, 1985b). These treatments would all be expe-
cted to attenuate the differences between the " -
endorphin state" after training and at the time of
retention testing. This state dependency interpretation
is based on evidence indicating that |3-endorphin is
released only after training. Training but not test
experiences, are followed by a decrease in brain
lo
/3-endorphin immunoreactivity/ which is not attri-
butable to inhibition of synthesis or increased intra-
granular degradation (Iz^uierdo et al.; 1984).
Thus the support for an important role of
peripheral E in modulating memory is considerable.
In addition to effects on memory/ the hormone also
has other central nervous actions/ such as influences
on electrographic arousal/ amygdala kindling/ cerebral
blood flow and central nonadrenergic activity. However/
the mechanisms by which the hormone might act on the
CNS/ to affect these functi6ns or to modulate memory
presents a problem because E does not cross the blood
brain barrier (BBB),
However/ E need not cause an alteration in
brain chemistry to produce behavioural effects. The
effects may be due to an influence on some peripheral
system.
Earlier it was suggested that the effect
of NE AND E might be due to the blockade of the adrenal
medullary secretions or the sympathtic response to
training (Gold/ McCarty and Sternberg/ 1981). However,
adrenalectomy does not cause amnesia in all cases
(Sternberg et al.; 1981). Nor does sympathetic blockade
with bretylium/ a peripheral sympathetic NE antagonist
lb
results in attenuation af this amnesia (Sternberg/
Gold and McGaugh, 1982).
There is extensive;evidence that hepatic glycogen
degradation is rapidly stimulated by a variety of horm-
ones which are released in response to different stimuli
(Goldfien, 1958; Exton and" Harper, 1975; Forsling et
al./ 1977). Stress states cause the release of a wide
range of hormones which exert catabolic effects on
the liver andSis found, tctv be one of them. It raises
blood sugar levels by a. direct action on the release
of glycogen from the liver. It stimulates hepatic glyco-
gen degradation at concentrations of M and greater
(Sherline et al./ 1972; Exton and Harper, 1975).
Recent evidence' suggests that hyperglycemia
subsequent to release or' injection of E contributes
to the hormone's actions on memory. E raises blood
sugar levels by a direct action on the release of glyc-
ogenfromtheliver.
The level of circulating glucose regulates the output of both insulin and glucagon. Low blood
sugar stimulates glucagon secretion while high blood
^ugar stimulates insulin "gecretion. However, there
is another mechanism regul-ating the output of is let's
1 7
Adrenaifne + + LIVER glycogen
Figure B Showing t.e «echan.s™ of resynthesising thelacti, acias to. iiver glycogen by E.
18
secretion, BS^-'l^ C-r*^ I*)
ZWs _ "T*..-J . _ ^These endocrine
t issues are richly innervated by the autonomic nerves
{Woods and Porte/ 1974/ Gerich et al., 1975) and respond
to sympathetic stimulation or the hormone E. E increases
the output of glucagon (o< - adrenergic activity) while
inhibiting insulin secretion ( adrenergic activity).
In this way, the important hyperglucemic action is favoured
in emergency situations. Under extreme stress, E not
only provides glucose to the circulation by glycogenolysis
but preferentially preserves it for utilization by the
brain since it simultaneously decreases insulin release.
Like glucagon, E increases the amount of active
phosphorylase in liver cells. It also promotes release
of acetate from muscle and glyceral from fat and these
provide materials for glycogenesis in the liver. Figure
II shows how the muscle glycoge^^ is broken down anaerO-
bically, in vigorous exercise, to lactic acid which
diffM^ii^^ into the blood and is resynthesisedfeglycogen
in the liver; with the help of epinephrine.
Several reports indicate that peripheral post-
trial injections of glucose also enhance memory storage
in a dose and time- dependent manner (Gold^ 1986; Gold
Vogt and Hall, 1986; Hall and Gold, 1986). A3 with E,
the dose response curve for glucose effects on memory
is an inverted U-function in which intermediate doses
enhance memory storage and the effects are time dependent (Gold,1986)
r>
SiG\o/gio>Ji act-iov o-f E" is -jreiea&e oVcujlatiV\g ^glucos^evels / it is possible that glucose represents part of the physiology by which E acts on memory. Cons-
istent with this view, Hall and Gold (1986) found that
plasma glucose levels show a footshock intensity related
increase soon after inhibitory avoidance training.
Further^ memory enhancing doses of glucose and E result
in increases (about 30%) in plasma glucose levels which
are similar to each other and to the values seen after
a training footshock. Thus these findings indicate
that relatively small increases in plasma glucose levels^
well within normal physiological limits, are corre-
lated with later retention performance. The similarities
in the behavioural properties of glucose and E and
the close relationship between post training glucose
level after footshock/ glucose or E injections/ there-
fore, suggest that hyperglycemia may be an important
component of E's action which modulate memory storage.
Further support for this view comes from the
findings in which memory enhancement with glucose was
found to be unaffected by pretreatment/ with adrenergic
antagonists (Gold^ Vogt and Hall, 1986). These findings
suggest that glucose modulation of memory storage is
beyond a relevant/ perhaps peripheral/ adrenergic rece-
ptor. Also, White and Messier (1988) found that glucose
can retroactively and non-contingently improve retention
in demeduJlated animals and do not'support the hypothesis
that the memory-improving action of glucose is due
to its effect on the adrenal medulla. Rather the effect
of glucose might be due to its action on the CNS. Unlike
E/ glucose is readily transported into the central
nervous system (Oldendorf^ 1971; PardL^idge and Oldendorf ^ t-M Cs y (X^t
1975). It is possible then that glucose^ directly on
the CNS to enhance memory. Consistent with this view,
Lee, Graham and Gold (1988)found that intraventricular
glucose injections can enhance memory storage for inhib-
itory avoidance training. The dose response curve has
an inverted Q form, as it does for peripheral injec-
tions of .E, glucose and several other memory.enhancing
treatments. Further the effects of glucose on memory are
time dependent. The findings are consistent with the
possibility that E responses to training modulate memory
by increasing circulating glucose levels and that
the increase in circulating glucose subsequent to increase
in E has central actions that regulate memory storage.
Ventricular glucose levels increase in response to
increases in circulating glucose levels. Unless glucose
acts directly at circumventricular sites (Cooper,
Beaty, Oppenheimer, Goodner and Petersdorf^ 1968),
21
elevations in ventricular glucose that follow circu-
lating glucose levels are not likely to contribute
substantially to neuronal glucose availability. Such
increases would be accomplished by cerebral vascu-
larization, which has far greater surface area in
contact with the CNS through which transfer of glucose
to neurons can be accomplished (G jedde, "J t ^ sen Silver /
1980; Hochwald, Gandhi and Goldman, 1983; Hochwald,
McShee and Ferguson, 1985). On the other hand/ injec-
tion of glucose directly into the lateral ventricle
TOiay be sufficient to increase glucose availability
in widespread brain regions. An additional possibility
is that central injections of glucose engage peripheral
sympathetic activation/ resulting in increases in
circulating E or glucose levels that mediate the effects
on memory.
Thus the behavioural and pharmacological findings
together with assessments of post-training plasma
glucose level support the view that the effects of
E on memory are mediated by its action on glucose.
The optimal memory enhancing doses of E and glucose,
derived from full behavioural dose-response curves
which have an inverted U-form; both result in elevated
9 ^
but physiologically rea'sonable plasma glucose levels.
Amnestic doses of E andi^g-^cose elevate glucose levels
to a significantly greajter and apprently supraphysio-
logical extent than do facilitating doses. Thus memory im/^t , modulation by E^oe relat-ed to the liberation of hepatic
glucose.
With this background we may pass on to the next chapter in which the effect of E and glucose
on memory has been re viewed-
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