emociones memoria y cerebro

8/18/2019 Emociones memoria y cerebro

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rain mechanisms of emotion and emotional learning

J oseph

E

LeDoux

New York

University, New York, New York, USA

The amygdala appears to play an essential role in many aspects of

emotional information processing and behavior. Studies over the past year

have begun to clarify the anatomical organization of the ainygdala and the

contribution of its individual subregions to emotional functions, especially

emotional learning and memory. Researchers can now point to plausible

circuits involved in the transmission of sensory inputs into the amygdala

between amygdaloid subregions and to efferent targets in cortical and

subcortical regions, for specific emotional learning and mem ory processes.

Current Opinion in Neurobiology 1992, 2:191-197

Introduction

Research

over the past 40 years has pointed to the amyg-

dala as the heart and soul of the brain’s emotional net-

work [l-5,6=*,7**]. Following Kluver and Bucy’s [8] oh-

servation that damage to the temporal lobe in monkeys

produced a variety of emotional disturbances, Weiskrantz

[9] demonstrated that damage to the amygdala alone

would also produce the syndrome. Subsequently, the

amygdala has been implicated in essentially every exper-

imental task that has been used to study emotional rep-

resentation in the brain. No other brain a rea has been

so consistently implicated in emotional processes

[lo**].

Although the amygdala is not the only structure involved

in emotion (see [11,12]), and emotion is not the only

function of the amygdala (see

[

13**] ), the amygdala is an

essential com ponent of the brain’s emotional system. The

following brief review of research during the past year

concerned with the brain mechanisms of emotion will

the&fore concentrate on the contribution of the amyg-

dala to emotional processes.

In spite of the clear involvement of the amygdala in emo-

tional functions, until recently little progre ss had been

mad e in understanding the functional organization of the

amygdala in emotion. In the older anatomical literature

the amygdala w as divided into two general subareas, the

basolateral and the cortico-medial groups. Today, the

amygdala is generally conceived in a far richer fashion,

often being divided into as many as ten or more subareas,

each with its own subdivisions and unique sets of affer

ent and effejent connections [14,15 ]. It is unlikely th at

emotion is mediated by the amygdala acting as a whole,

or even as a two-part collection of nuclei, and it is neces

sary to isolate the contribution of individual subarea s to

different aspects of emotional functions. The emphasis of

this review will therefore be on recent advances in our

understanding of the anatom ical organization of individ-

ual amygdaloid subareas and the role of these subareas

-,

-;. -

I.

.I

.:

’ L,

A

in emotiona l functions, esp ecially emotional learning and

memory.

Anatomical organization of the amygdala

The emotional functions of the amygdala critically de-

pend upon the reception of sensory inputs. Many of

the sensory projections to the amygdala terminate in

the lateral amygdaloid nucleus. These projections origi-

nate mainly in the sensory processing areas of the cor-

tex and thalamus. W hile the cortico-amygdala projec-

tions had been well characterized at the light micro-

scopic level [14,16,17], much less was known about the

thalamoamygdala projections.

Recent studies by my colleagues and I have shown that

the auditory projection to the lateral amygdala from the

thalam us originates primarily in the posteri or intralami-

nar nucleus, a thalamic cell group that receives auditory

inputs from the inferior colliculus and is associated with

the medial geniculate body (Fig. 1) [ 181. About half of

the thalamo-amygdala projection neurons in this region

can be labeled with an antibody against glutamate, sug-

gesting that neural transmission in this pathway may be

mediated by this excitatory amino acid transmitter sub-

stance [19 ]. Furthermore, the synaptic profile of these

terminals [20**] is similar to that of glutamate-containing

terminals in this region (CR Farb and JE LeDoux, unpub-

lished data). The above studies provide the most detailed

understanding to date of the morphology of any sensory

projection to the amygdala.

Sensory transmission to the amygdala from the thalamus

is not limited to the auditory modality. An extensive study

of thalamwamygd ala projections across sensory modal-

ities has been carried out by Turner and Herkenham

[21 ]. Radiolabeled amino acids were injected into var-

ious thalamic nuclei and transport to the amygdala was

Abbreviations

LTP-long-term potentiation; NMDA-N-methyl-o-aspartic acid; Pha-L-fhaseolus vulgaris leucoagglutinin

@ Current Biology Ltd ISSN 0959 4388

191


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192 Cognitive neurosc ience

Arousal and plasticity

Lemniscal

auditory

pathways

Extralemniscal

auditory

pathways

Behavioral Autonomic Endocrine

Emotional response control systems

Fig. 1. A diagram illustrating some of the pa thways underlying emotional informatton processing and response control by the amygdala.

Pathways through whic h auditory inputs a re transmitted to the amygda la are shown but similar circuits a lso exist for other sensory

systems. Tonotopica lly organized auditory signals are transmitted to the auditory thalamus over lemnisca l pathways, which synapse

in the ventral d ivision of the medial geniculate body (M I. Extralemniscal pa thways transmit to other parts of the auditory thalamus,

including the medial division of the media l geniculate body (MC m) and the posterior intralaminar nucleus (PIN). While MG v only projects

to primary a uditory cortex, MCmiPlN projects to both primary and assoc iation areas of auditory cortex, as well as to the lateral nucleus

of the amygdala (AL). The thalamo-amygda la projection forms asymmetric, excitatory (+ 1contacts with AL, contains glutamate (C lu),

and may use this excitatory substance as a neurotransmitter. Thalamo-amygda la projections have been implicated in emotional learning,

and high-frequency stimulation of these projections produces long-term potentiation (LTP) in AL. Auditory and polymodal assoc iation

areas relay auditory signals to AL by way of the external ca psule. These pathways are also involved in emotional learning and exhibit

LTP. AL projects to the basolateral nucleus of the amygdala (ABL), which projects wide ly to corttcal a reas (not shown) and to the central

nucleus of the amygdala (A CE). ACE has extensive connec tivity with brainstem areas involved in the control of emotional responses. It also

projects to the nucleus basalis, which projects wide ly to co rtica l areas. The pathway from the nucleus basalis to cortex uses ac etylcholine

(AC h) as a neurotransmitter. Cholinergic transmission to the cortex from the nucleus ba salis has been implica ted in co rtica l arousal a nd

plasticity.

examined. Their findings show that the amygdala receives

subcortical inputs from a wide variety of sensory systems.

emotional situations. Direct projections to the amygdala

have not figured prominently in contemporary thought

about the neural basis of emotion, which tends to focus

ThalamWam ygdala projections have been implicated in

on corticcramygdala systems [l-5,7-,13-]. The classic

emotiona l learning processes , especially fear condition-

theories of Cannon [22], Bard [23] and Papez [24],

ing (see [6**] ). Thalamic inputs to the amygdala allow

however, emphasized the importance of subcortical sen

sensory signals to activate it either before or simulta

sot-y transmission in the experience and expression of

neous with the arrival of signals at the cortical level,

emotion. These theories suggested that the hypothala-

and may therefore play an important role in precon-

mus, when activated directly by sensory projections from

scious and precognitive emotional processing. Because

the ventral thalamus, gave rise to emotional behavior

these projections exit the primary sensory systems at

by way of projections to the brainstem and gave rise

an early stage of processin g, they are unlikely to en-

to subjective emotional experiences by way of projec-

code complex stimulus representations. They may allow

tions to the cerebral cortex. The finding of extensive

primitive sensory representations to rapidly activate the

subcortical sensory innervation of the amygdala by thala-

amygdala, however, which may be important in certain

mic projections fits well with the spirit of these theories,


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Brain mec hanisms of emotion and emotional learning LeDoux

193

even if the anatomical details (thalamo-amygdala versus

thalamo-hypothalamic projections) are different.

Our knowledge of anatomical interactions between

thalamwamygd ala and corticcl-amygdala connections is

in its infancy, but prog ress in this area is essential for

understanding how the amygdala integrates diverse sen-

sory inputs in emotiona l information processin g. Within a

given sensory m odality, the two projection systems over-

lap and may in fact converg e in the lateral nucleus [25-l,

Convergence would allow thalamic and cortical sensory

inputs to act on common ensembles of amygdala neu-

rons, and would place the lateral nucleus of the amyg-

dala in a key position to coordinate the flow of sensory

information that ultimately leads to emotional reactions.

Given that much o f the sensory ctierentation of the amyg-

dala is by way of the lateral nucleus, connections from

this nucleus to other amygdaloid regions must play an

important role in the emotional processing functions of

the amygdala. Until recently it had been technically cum-

bersome to study the intrinsic organization of the amyg-

d&. The problem is that its subregions occupy small

volumes and therefore it is diffkult to restrict the injec-

tion of tracer substances to one region. T he introduc-

tion of the Pbaseolus vulgaris leucoagglutinin (Pha-L)

axonal transport neural tract-tracing method [261, which

allows for the placement of very restricted injection sites,

identification of cells involved in uptak e and transport,

visualization of full axonal arboriza tions, and identifica-

tion of synaptic boutons at the light microscopic level,

has solved this problem and has provided some new

insights into amyg dala organization. Pittinen and Am aral

[27**] placed injections of Pha-L into the lateral nucleus

and demonstrated a previously unknown projection to

the basolateral nucleus in primates. Studies in rats have

confirmed the existence of this projection (JE Ledoux,

CR Farb, L Steffanacci, G Go, A Pitkanen and DG Amaral,

unpublished data). These observations are of significance

for several reasons . First, unlike the lateral nucleus, the

basolateral nucleus projects heavily to cortical association

areas [14,27-l. Sensory information reaching the lateral

nucleus from either cortex or thalamus can thus influence

on-going cortical processing by way of the lateral to ba-

solateral projections. Secon d, unlike the lateral nucleus,

the basolateral nucleus projects heavily to the central nu-

cleus of the amygdala [14,151, which, as described below,

provides a link by which sensor)i inputs to the lateral

nucleus can activate emotional behaviors and autonomic

response s, and can influence cortical arousa l.

Functional spec ialization within the amygdala

As described above, most of the sensoty projections to

the amygdala terminate in the lateral amygdaloid nucleus.

It might be expected that lesions of this structure would

disconnect the amygdala from environmental informa-

tion and therefore reproduce the disruptive effects on

emotional functions of both large amyg daloid lesions, in-

volving several subregions (including the lateral nucleus),

and small lesions o f other subregions of the amygdala.

Recent studies have in fact shown that lesions confined to

the lateral nucleus prod uce the predicted ‘disconnection’

effects in several different behavioral tasks. One study of

rodents involved classica l fear conditioning, a proce dure

whereby an affectively neutral stimulus, such as a tone,

is paired with a footshock [281. After several pairings

the tone elicits emotional (fear) reactions, such as ‘freez-

ing’ and changes in autonomic activity. A large sample

size was necessary to generate a small group with ac-

ceptable lesions, i.e. lesions that completely destroyed

the lateral nucleus at a designated level of the amygdala,

and that did not encroach upon the central nucleus of

the amygdala, a structure that is known to be necessary

as an amygdaloid output in the expression of emotional

respons es [2 +3l]. Similarly, studies of non-human pri-

mates have shown that subtotal lesions of the amygdala

that encroach upon th e lateral nucleus produce the loss

of fear and other components of the Kliiver-Rucy syn-

drome [32*-l.

The lateral nucleus has also been it?ipli&@ .in appet-

itive emotional reactions, particula@ .conditioned place

preference learning in rodents [33**,34*0]. Conditioned

place preferences are established by providing reinforc-

ing stimulation in a certain location. This can be done

with either primary reinforcers (such as desirable foods)

or by chemical or electrical brain stimulation. Lesions of

the lateral/basolateral amygdala interfere with the forma-

tion of these conditioned place preferences. The effect of

the lesions appears to involve the interruption of the flow

of sensory information from the lateral/basolateral region

to the nucleus accumbens, where sensory information

may normally be associated with reward information by

interactions with dopam ine containing terminals.

Thus, the lateral nucleus of the amygdala, by virtue of

its input from sensory processing structures, appears to

be involved in both place preference formation and fear

conditioning, but seems to use different e&rent projec-

tions in these forms of learning; place preferences appear

to involve projections to the nucleus accumbens and fear

conditioning involves projection s to the central nucleus

of the amygdala.

The central nucleus of the amygdala is not exclusively

involved in aversive emotiona l learning. Recen t studies by

Gallagher, Graham and Holland [35**] show that it is also

involved in appetitiv e conditioning. IJsing a task whic h

separates out conditioned responses related to the con-

ditioned stimulus, and those related to the unconditioned

stimulus, they found th at central nucleus lesions selec -

tively impaired conditioned-stimulus related responses.

This kind of behavio ral analysis has not yet been per-

formed for other conditioning paradigms.

The central nucleus of the amygdala, by way of its ex-

tensive connectivity with brainstem areas, is believed

to play an important role in the expression of behav-

ioral and autonomic responses associated with emotional

arousal. This notion was first demonstrated in studies of

conditioned bradycardia by Kapp and coworkers [29],

and later extended to several other response modalities

[30,31]. More recent studies by Kapp’s group [36*-l have

shown that the central nucleus also plays an important

role in regulating the state of arousal of the neocor-

tex. Thus, electrical stimulation of the central nucleus

produces cortical electroencephalogram desynchroniza-


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tion. As this effect is abolished by systemic administra-

tion of the cholinergic antagonist atropine, it is believed

that connections from the central nucleus to the cholin-

ergic neurons of the nucleus basalis, which projects

widely to the neocortex, mediate these changes. This

cholinergic arousal system may allow emotional infor-

mation processing by the amygdala (particularly by the

lateral-baso later&c entral connection) to influence per-

ceptual, attentional, memory, and other cognitive pro-

cesses mediated at the neocortical level.

Kapp’s observations of an amygdala-mediated cholinergic

arousal of cortex are in close accord with Weinberger’s

[37**] recent suggestion that learning-induced changes in

the receptiv e field functions of neurons in auditory cortex

critically involve parallel transmission and convergen ce of

two pathways: pathway one, a specific (lemniscal) relay

of tonotopic auditory information from the ventral divi-

sion of the medial geniculate body to the auditory cortex;

and pathway 2, an extralemniscal relay from the medial

areas of the medial geniculate body to the amygdala,

which then projects to the nucleus basalis, which p rojects

widely to cortex. Weinberger proposes that pathway 2

enters into ‘Hebbian synapses’ with pathway 1 and as

a result modifies the receptive fields of the involved

neurons. More specifically, the thalamo-amygdala pro-

jection to the nucleus basalis increases the postsynaptic

excitability of pyram idal cells in auditory cortex (cells

that receive the frequency-specific inputs from the ven-

tral division of the medial geniculate body), and thereby

changes the strength of inputs of that frequency. Thus,

thalam cl-amyg dala transmission is not only essential for

subcortical emotional learning and non-specific arousal

(see above), but may also contribute to highly specific

plastic modifications occurring in the cerebral cortex.

Cellular mec hanisms of emotional learning in

the amygdala

It is widely believed that synaptic plasticity underlies

the rapid induction of memories through experience

(see [3%40 ]). One of the most extensively studied

models of synaptic plasticity is long-term potentiation

(LTP) [41-43], which involves an increase in the eff-

cacy of synaptic transmission as a result of high fre-

quency (tetanizing) stimulation of an afferent pathway.

In some hippocam pal pathways, LTP is mediated by ex-

citatory amino acid receptors [41-43]. It is thus signifi-

cant that the excitatory amino acid, glutamate, is present

in the cells of origin of at least some sensory inputs

to the lateral nucleus of the amygdala [ 19**], and that

excitatory amino acid receptors are highly concentrated

in the lateral/basolateral region [44]. Further, LTP has

been induced in the lateral/basolateral amygdala by stim-

ulating thalameamygdala projections n zt zlo 45], and

corticwamygdala projections (the external capsule) in

v tro [46]. Lesions of the lateral nucleus interfere with

fear conditioning [28] and blockade of N-methyl-D-as-

pat-tic acid (NMDA ) receptors in the lateral/basolateral

amygdala interferes with the acquisition [47**] of fear

conditioning. It has also been show n that intraventric-

ular injections of NM DA antagonists interfere with the

acquisition but not the expressio n of fear conditioning,

presumably by acting in the amygdala [48-l.

Collectively, these findings suaest that excitatory amino

acid receptors in the amygdala may play a rU id role

in synaptic transmission and synaptic plasticity in the

sensory projections to the amygdala, and in emotional

learning processing mediated through th ese projections.

A recent

n v tro

study of LTP, however, suggests that

synaptic plasticity in the amygdala is not mediated by

NM DA receptors [49**]. Because of the important im-

plications of this finding, it needs to be considere d in

some detail. Several points should be noted. First, the

study involved stimulation of the external capsule, w hich

contains fibers from many areas o f the neocortex. It is not

known whether all or only some of the projections trav-

eling through the external capsule are plastic. Selective

tetanization of the individual cortical areas that project to

the amygdala would be useful. Second, given the diverse

origins of the fibers stimulated, it is possible that NMD A

and non-NMDA (and possibly even non-excitatory amino

acid) mechanisms are involved in the overall effect. In the

hippocampus, LTP in some p athways is NMD A depen-

dent while in others it is not. If multiple mechanisms are

involved in external capsule LTP, blockade of only the

NM DA receptors would not completely block LTP. Fu-

ture studies should determine which substances are used

in normal transmission and synaptic plasticity by projec-

tions from individual cortical areas. Third, the recordings

were m ade in the lateral and basolateral nuclei. The cor-

tical inputs to the lateral and basolateral nuclei a re very

different. The lateral nucleus receives m uch of the direct

sensory innervation from cortex and thalamus and then

projects to the basolateral nucleus, which also receives

tierents from non-sensory association regions. Careful

comparisons therefore need to be made between synap-

tic plasticity in the lateral versus basolateral areas. Fourth,

even if corticcramygdala LTP turns out not to involve

NM DA receptors, the case would still be open with re-

spect to thalamo-amygdala projections. Thus, although

the observation that blockade of NM DA receptors in the

lateral/basolateral amygddki fails to interfere with LTP is

one of the most important findings of the past year, its

implications for understanding synaptic plasticity in the

amygdala should not be over interpreted at this point.

This area of work has just begun and much more work

needs to be done.

Regardless of the mechanism, amygdala LTP is extremely

important. It is induced in pathways that are known to

have clear roles in well characterized and specific learning

processes. Like LTP, the conditioned associations medi-

ated by the amygdala are rapidly learned and long last-

ing. Furthermore, the stimulation conditions of LTP are

similar to the stimulation conditions of the associative

conditioning tasks that have been used to implicate the

amygdakd in emotional learning and memory processes.

This close correspondence between LTP and behavior

has been lacking for the hippocampus and has hindered

progress in relating hippocampal LTP to real-life learn-

ing and memory phenomena. Although the amygdh will

always lack the convenient anatomical organization of

the hippocampus, studies of amygdala LTP may help to

uncover basic mechanisms through which normal and


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Brain mechanisms of emotion and emotional learning LeDoux 195

pathological emotional memories are formed, and may

also be useful as a model system for furthering our un-

derstanding of the relationship between LTP and mem-

ory.

ral and Chemical Control. Edited by Oomur Y. Tokyo:

apan

Scientific Societies Press; 1986: 325-344.

6.

. .

LEDOUX JE: Emotion and the AmygdaIa. In The Am.y&zla:

Neurobiokgical Aspects ofEmotio?z, Memov and Mental Dys

juzction.

Edited by Aggleton J. New York: Wileytiss; 1992, in

press.

Conclusions

The amygdala has long been view ed as playing an impor-

tant role in emotion. In recent years, however, there h as

been an explosion of research aimed at understanding

the anatomical organization of this structure and its con-

tribution to emotion . New findings relating to the organi-

zation, especially those concerned with how sensory in-

puts reach and are subsequently distributed throughout

the amygdala, have been especially helpful, as they begin

to provid e, in broad outline, an anatomi cal understanding

of the input-output relations t hat underlie information

processing by this structure. Projections to the amygdala

from sensory processing areas of the thalamus are much

more extensive than previously thought and appear to

be important in emotional learning, as expressed behav-

iorally, and may also contribute to cortical arousal and

plasticity in emotional situations. Although blockade of

NM DA receptors in the amygdala does not interfere with

LTP, there a re many possible reasons why this may be

so, and it is too early to conclude that the amygdala does

not have an NMD A-mediated form of LTP. The actual

mechanism of LTP in the amygdala is not as important

as the fact that we can now ask questions about the

mechanisms of synaptic plasticity in a structure with such

a clear role in a well characterized learning and mem ory

phenomenon. That this phenomenon plays such a cen-

tral role in normal mental life mak es this an especially

attractiv e system fo r future inve stigation.

A thorough review of the involvement of the ,amygdala in behavioral

tasks used to study emotion in experimental animals. This review shows

that the amygdala has been implicated in essentially every such task.

7.

. .

HALGRFN E: Emotional Neurophysiology of the AmygdaIa

within the Context of Human Cognition. In 7hc

Am_ygdala:

Neurobiological A.spects of Emotion, Memory. and Mental 0~1s~

function. Edited by Aggleton J. New York: WileyLiss; 1992, in

press.

An excellent review of research on the role of the human amygdala in

emotion. The review points out certain discrepancies between findings

from human and animal research. These discrepancies need to be ac

counted for.

-,

8. KI.~NER H, BUCY P: “Psychic BIindnesSj’.,a@,Other Symp-

toms Following Bilateral TemporalZol&tom+ in Rhesus

Monkeys.

Am J Pbysiol 1937,

119;2?2;353. “-

9.

WEIXR~NTZ L: Behavioral Changes Associated with Ablation

of the Amygdaloid Complex in Monkeys. J Camp Pbysiol

~sychol 1956, 49:381-391.

10.

LEDorrx JE: Emotion and the LImbic System Concept. Con-

. .

cepts

Neurosci 1991, 2~169-199.

A critical discussion of the limbic system concept as it relates to emo-

tion. The paper concludes that the so-called limbic system, which is

difficult to define, has little to do with emotion and that the survival of

the limbic system hypothesis of emotion is in large part due to the fact

that the amygdala is part of this system.

11.

PANKS~PP : Toward a General Psychobiological Theory of

Emotions.

Beball Brain Sci

1982, 5:407467.

12. SIE ;ELA, EIXNGER H: Neural Control of Aggression and Rage

Behavior. In

f~andbook of the tf@othalamus,

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ies of the H@othalamtu. Edited by Morgane PJ, Panksepp J.

New York: Marcell Dekker; 1982, 3:203-240.

cknowledgement

13.

AGGLE’I’ON: The

Am&ala- Neurohiological Aspccl.s of Emu

. . tion, Memoq: and Mental Dysjunction. New York: Wiley-L&;

1992, in press.

Supported by LJS Public lkalth Service Grants MH38774 and

MH465IG.

,

A comprehensive collection of chapters on the structure and function

of the amygdala. It is the most thorough survey of the amygdala available

toddy.

14.

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dala may play an imporrant role in the integration of sensory signals of

vatying degrees of complexity in the initiation and control of emotional

reactions.

26.

GERFEN CR, SAWCIIENKO PE: Anterograde Neuroanatomical

Tracing Method that Shows the Detailed Morphology of

Neurons, their Axons and Terminals: Immunohistochemical

Localization of Axonally Transported Plant Lectin, Phaseo-

lus Leucoagglutinin. Bruin Kes 19X4, 290:21F238.

27.

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PI’I’KANEN , AMA&U DG: Demonstration of Projections from

the Lateral Nucleus to the Basal Nucleus of the Amyg-

dala: a PH.&L Study in the Monkey. fZz@ Rrain Rcs 1991,

83:465-470.

This study identifies a previously unknown projection from the lateral

to the basolateral nucleus of the amygdala and clarifies how sensor)

inputs tllat reach the lateral nucleus get distributed to other amygclaloid

regions and to cortical association areas.

28. LEIX~I’X E, Crccr~r;‘rr‘i P, XA~URARISA, ROMANSKI M: The Lat-

eral Amygdaloid Nucleus: Sensory Interface of the AmygdaIa

in Fear Conditioning. ./ Nccurosci 1990, 10:1062~1069.

29. KVV BS. P&Avth M, III’KHCOCK JM, ROSEN JB: Anxiety and the Amyg-

dala: Pharmacological and Anatomical Analysis of the Fear-

Potentiated Startle Paradigm. In 7& Pvc/&om oJ’Learning

and I fotit~ation.

Edited by Bower GH. San Diego: Academic

Press; 1987.

31

L~Dor’x JE, IWATA J, Ctcc~~e’rri P, REIS DJ: Different Pro-

jections of the Central Amygdaloid Nucleus Mediate Au-

tonomic and Behavioral Correlates of Conditioned Fear. .I

Nrurosci 198. $ 8:2517-2529.

32.

ZOL. MORG. Y S, SQUIRE LR, P, CLOWER RP: In-

. .

dependence

of Memory Functions and Emotional Behavior:

Separate Contributions of the Hippocampal Formation and

the AmygdaIa. Hippocampus 1991, 1:207-220.

This is an excellent study showing for the first time that subtotal lesions

of the primate amygdala could produce the emotional changes of the

Kli_iver-Bucy syndrome and at the same time not produce the cognitive

memory deficits, which appear to he more related to the hippocampai

fommation.

33.

IIIKOI NM, WHITE EL: The Lateral Nucleus of the Amyg-

. .

dala Mediates Expression of the Amphetamine Conditioned

Place Preference. J

Nrurosci 1991, 1 I:2107~2116.

Previous studies had implicated the lateral nucleus as the sensory ins

t&ace of the amygdala in fear conditioning (see [28] ). This study, tom

gether wtth that of Eve&t and colleagues [34**] shows that the lateral

amygcidloid nucleus is an essential component of appetitive as well as

aversive emotional learning circuits.

34.

E\‘FNTT BJ, MOKIUSKA, O’BKIEN A, ROH~INS TW The Baso-

. .

lateral AmygdaIa-Ventral Striatal System and Conditioned

Place Preference: Further Evidence of Limbic-Striatal Inter-

actions Underlying Reward-Related Processes. Neuroscience

1991, 42:1-l&

Prevtous studies had implicated the lateral nucleus as the sensory inter-

face of the amygdala in fear conditioning (see [281). This study together

with that of Hiroi and White [33*-j shows that the lateral amygdaloid

nucleus is an essential component of appetitive as well as aversive emo~

tional learning circuits.

35.

GALLAGHER M, GIUIIAM PW, HOIIAND C: The Amygdala Cen-

. .

tral Nucleus and Appetitive Pavlovian Conditioning: Lesions

Impair One Class of Conditioned Behavior. ,I

Neurosci 1990,

105:19061911.

A novel behavioral analysis, pioneered In previous work by Holland, is

used to teaye apart the contribution of the central nucleus of the amyg

dala to conditioned responses r&ted to a conditioned stimulus versus

an apprtttwe unconditioned stimulus, The study also shows that the

central nucleus of the amygdala contributes to appetitive conditioning.

36.

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KAPP

BS,

WHAIRN

PJ, S~II’PL~~F, Pkscot: JP: AmygdaIoid Con-

tributions to Conditioned Arousal and Sensory Information

Processing. In 7br At? )r&kz~:

Neur(hiohgical hpccts of

mo

tion. .Memq~ and Mcwtal Dy@nctiort. Edited by Aggleton J.

New York: Wiley Liss; 1991:229-254

This chapter reviews recent work by Kapp’s lahoratoty on the contri-

bution of the central nucleus of the amygdala to cortical arousal pro-

cesses. Of special significance is the presentation of findings showing

that stimulation of the central nucleus of the amygdala produces cortical

arousal (electroencephalogram desynchronizdtion) and that this effect

is blocked by systemic administration of the cholinergic antagonist at-

t-opine. The authors propose that central nucleus stimulation activates

the cholinergic neurons of the nucleus basatis, and that this system,

which projects widely to cortex, 1s responsible for the cholinergically-

mediated arousal effects.

37.

WEINI~EK~;FH , ~HE J, ME’I’HEKATE , MCKENNA T, DIAMOND

. . D, BAKINGJ, LENNARZKTZ, Ckss~u,u

J: Neural Adaptive Infor-

mation Processing: a Preliminary Model of Receptive-Field

Plasticity in Auditory Cortex During Pavlovian Condition-

ing. In Leurning and Computational Neuroscience: Fowzah

fions of Adaptive Netulorks. Edited by Gabriel M , Moore J.

Cambridge, MassachusettS: MIT Press; 1990:91-138.

This chapter reviews the work of Wemherger’s lahoratoty on recepnve

field plasticity in auditoty cortex during aversive classical conditioning.

Of particular relevance, especially in light of the findings by Kapp and

associates (see [36**] ), is the suggestion that receptive field piasticity

depends upon cholinergic transmission to the cortex from the amyg-

dala by wdy of the nucleus hasalis.

38.

SQCIIKFLR:

Memory: Neural Organization and Behavior. In

Handbook ofPbysiolo~.1: The Nert~ous System Higher Func-

tions oJ the Bruin. Edited by Plum F. Bethesda: Americdn

Physiological Society; 1987, 5:29>371.

39.

I~\YXINS RD, CII\KK GA, KANDELER: Cell Biological Studies

of Learning

in Simple Vertebrate and Invertebrate Systems.

In Ham&wok oj’ Physiology, 1: T e Nertjous System. Higher

Functions of‘the Brain. Edited hy Plum F. Bethesda: American

Physiological Society; 1987, 5:25-83.

40.

ECCIESJC: Mechanisms of Learning in Complex Neural Sys-

tems. In

Hundbook of Physiology I: The Nenwls gcrtem.

Higher Functions of the Bruin. Edited by Plum F. Bethesda:

American Physiological Society; 1987, 5:137-167.


7/7

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197

41.

42.

43.

44.

45.

46.

47.

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BROWN TH, CHAPMANPF, KAKGS EW, KEENAN CL: Long-Term

Synaptic Potentiation. Science

1988, 242:724-728.

TEYLER J, DISCENNA : Long-Term Potentiation.

Annu Rezl

Neurosci 1987, 10:131&161.

COTMANCW, MONAGHANDT, GANONG AH xcitatory Amino

Acid Neurotransmission: N MDA Receptors and Hebb-Type

Synaptic Plasticity. Annu Recj Neurosci 1988, 11:61-80.

MONAGHANDT, COTMAN CW:

Distribution of N-Methyl-D-

Aspartate-Sensitive L-(3H)Glutamate-Binding Sites in Rat

Brain.

J Neurosci 1986, 5:290+2919.

CLUCNETMC, LEDOL~XE: Synaptic Plasticity in Fear Condi-

tioning Circuits: Induction of LTP in the Lateral Nucleus

of the Am ygdala by Stimulation of the Medial Geniculate

Body.

J Neurosci 1990, 10:281%2824.

CHAPMAN PF, KAIRISS EW, KENNAN CL, BROWN TH: Long-

Term Synaptic Potentiation in the Amygdala. .~ynapse990,

6:271-278.

MISERENDINOJD, SANANES B, MEUA KR, DAVIS M: Blocking

of Acquisition but not Expression of Conditioned Fear-PO-

tentiated Startle by NMDA Antagonists in the Amygdala.

Nature 1990, 345:71&718.

This study shows that NMDA receptors in or near the amygdala play

an essential role in emotional learning. This fits well with the growing

evidence of synaptic plasticity in the amygdala (see [45,46] 1.

48.

KIM

J, DECOLA JP, LANDER FERNANDEZ, FANXELOW S: N-

. .

Methyl-D-Aspartate Receptor Antagonist APV Blocks Acqui-

sition but not Expression of Fear Conditioning. Behall Neu-

rosci 1991, 105:16&167.

This study involves i.ltraventricular injection of 2~amino-5.phospho-

nopentanoate (Al%‘) and is thus ambiguous as to where the action oc-

curs. Together with the study by Miserendion et a(. [47**], however,

one can speculate that the effects occur in the amygdala. If so, the two

studies would support each other in implicating NMDA receptors in

fear conditioning.

49.

CHAPMANPF,

BELLAVANCEL.:

nduction of Long-Term Poten-

. .

tiation in the Basolateral Amygdala does not Depend on

NMD A Receptor Activation. Synapse 1992, in press.

This study is potentially damaging to the hypothesis that synaptic plas

ticity

in the amygdala underlies emotional learning, and that both synap-

tic plasticity and emotional learning depend upon NMDA receptors (see

[47**] ). This is not the only form of LTP that has been demonstrated

in the amygdala, however, and the findings only show that this form

is independent of NMDA receptors. It is still possible Fiat an NMDA~

dependent form of LTP will be found. Regardless. Of, the mechanism,

amygdala LTP is a new and exciting research a& th% bffefs new pos-

sibilities in understanding cellular mechanis,??

of

e onal memory

and in relating synaptic plasticity to normal;raemory processes.

JE LeDoux, Center for Neural Science, New York University, 6 Wash-

ington Place, New York, New York 10003, USA.

emociones memoria y cerebro

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