Download THE EMOTIOGENIC BRAIN STRUCTURES IN CONDITIONING

ACTA NEUROBIOL. EXP. 1979, 39: 503-516
Lecture delivered at the Warsaw Colloquium o n Instrumental
Conditioning and Brain Research
May 1979
THE EMOTIOGENIC BRAIN STRUCTURES IN CONDITIONING
MECHANISMS: CONDITIONED EVOKED POTENTIALS AND MOTOR
RESPONSES
R. Yu.ILYUTCHENOK
Institute of Physiology, Siberian Branch of the Academy of Medical
Sciences of the USSR, Novosibirsk, USSR
Abstract. The emotiogenic rnorphofunctional control system consists
of the amygdaloid complex \(AM), the zona incerta, the peri- and paraventricular nuclei of the hypothalamus and the midbrain central gray
matter (CG). The neuronal relationships between the structures of this
system were established. Lesions of these structures prevented one-trial
learning, whereas electrical stimulation of the AM or the CG permitted
retrieval of a trace which was lower than threshold. AM stimulation
accelerated learning 'by 5-10 times. The possible mechanisms of the
emotiogenic control system of memory' are discussed. The contributim
of the identified structures of the emotiogenic control system of memory
was quantitatively estimated, by employing a matrix of the interaction
of these structures during the performance of conditioned aeurographic
responses of the radial nerve. The approach established the role of the
emotiogenic control system in the spatial-temporal organization of brain
structures needed for the retrieval of conditioned motor responses. Weakly trained cats, in which the AM-CG had been stimulated, did not differ
from well trained ones in the patterns and correlation matrices of the
conditioned evoked potentials. AM-CG activation may accelerate learning by reproducing such spatial-tkmporal relationships that are characteristic of well trained animals.
Ample evidence for the important role of emotions in memory has
come from recent studies. However, it is not clear how emotions contribute to this process. Specifically what makes the mechanisms of the
emotions-memory interaction difficult to identify? Gaps exist in our
knowledge of:
1. The spatial-temporal patterns of the system of emotiogenic structures involved in memory control.
2. The relative contribution of each emotiogenic structure and the
interaction of these structures during conditioning.
Further, there remain open questions of:
1. What changes are elicited by the excitation of emotiogenic structures, and in which brain regions?
2. What determines the i~nfluenceof emotiogenic structures on memory: the activation of the emotiogenic structures during the presentation of the unconditioned stimulus, or the brief residual process in
these structures, or even long-term retention (perhaps, for life) of memory in the emotiogenic structures?
It is difficult to provide an accuate assessment of the control system
of memory because each brain structure contributes specifically to conditioning. To evaluate the structures composing this system, a more
rigorous criterion is needed than the #degree of changes in conditioned
responses acquired as the result of repeated pairings. The limit of memory trace control is information fixation at its first presentation, that
is me-trial learning. Our analysis of one-trial learning was based on
a model of the passive avoidance conditioned response. As a result, we
identified those lesions of brain structures which disturb the elaboration
of this response.
It has been reported that the amygdaloid complex (AM) (11, 14) and
the ventrolateral region of the midbrain central gray matter (CG) (7) are
substrates for one-trial learning. In our laboratory L. Loskutova and
I. Vinnitsky (unpublished) have shown that rats with lesions of CG
become immuned to one-trial learning when shocked with moderately
(0.75 mA) or even very painful (1.5 mA) current. This has also been
observed in amygdalectomized rats. It has been suggested that these
structures may be integrated into a structural-functional emotiogenic
system that controls memory processes.
What structures and pathways compose the amygdaloid complexcentral gray (AM-CG) system? Fibers, which connect the AM with the
subcortical brain structures (Fig. I), are the ventral amygdalofugal
pathway (VAF) and the stria terminalis (ST). The VAF ends in the
lateral preoptic and anterior-hypothalamic regions. The ST ends in the
medial preoptic and anterior-hypothalamic regions. L. Loskutova and
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Fig. 1. The emotiogenic regulatory system of memory in the rat. Lesions of the AM, the ST, the HPV, the CG completely prevent one-trial learning. Lesions of the VAF and the ZI prevent it only under moderately aversive stimulation. Current intensity: I, 0.75 mA; 11. 1.5 mA. 1, third day of familarization; 2. testing 24 h after learning; 3,
testing 48 h after learning. White columns, for control rats; black column, for lesioned rats.
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I. Vinnitsky demonstrated that sections of either of these two pathways
make rats incapable of one-trial learning.
Thus, it suffices to transect the VAF a t the level of the preoptic area
and the anterior hypothalamus to prevent the emotional response and
the elaboration of the passive avoidance conditioned response in rats
that received moderate footshock (0.75 mA). The integrity of the VAF is
most probably needed for the appearance of the emotional response and
its autonomic component. There are other data supporting this suggestion. Thus, stimulation of the sites of passage of the VAF fibers eliclts
a defensive response with components of alertness and fear. Sections of
the VAF in the preoptic and the anterior hypothalamic regions prevent
the development of the response to AM stimulation (4).
However, in our experiments, section of the VAF at the level of the
preoptic area did not prevent me-trial learning when a strong footshock
(1.5 mA) was delivered. Rats also did not lose the capacity for multi-trial
learning after section of the VAF. Section of the VAF at the level of
the caudal hypothalamus had no effect on one-trial learning. Clearly,
the VAF is not the only pathway through which the AM influences
memory.
Bilateral sections of the ST prevented me-trial learning as well
(Fig. 1). It is important to note that such a section made rats incapable
of one-trial learning, even under the stmng footshock condition (1.5 mA)
that resulted in learning in all animals of the control group. Indeed,
it 1s noteworthy that the peri- and paraventricular nuclei, that is the
primary sites where the ST ends, are the critical nuclei of the preoptichypothalamic region in one-trial learning. Lesion of these nuclei prevented one-trial learning t m , in spite of stmng footshock (Fig. 1).
The integrity of zona incerta (subthalamus) is another significant condition ensuring one-trial learning. It should be emphasized that lesions
of zona incerta prevented one-trial leanning only when a moderate footshock was delivered (Fig. 1). Under stronger stimulation, (1.5 mA current), one-trial learning was still possible; however the elaboration of
some autonomic and motor components of the conditioned defensive
response was poorer, as observed by N. Volf and S. Tsvetovsky (unpublished) in our laboratory.
Thus, the system of emotiogenic nuclei essential for one-trial learning
(Fig. I), and comprising the AM, preoptic area; z. incerta, peri- and paraventricular hypothalamic nuclei, the CG (the AM-CG system). In the
case of the fixation of emotionally colored information, its biological
meaning is perceived at the first presentation. The role of the AM-CG
system is manifest in the course of linkage between memory trace and
the retrieval program.
Ln the case of repetitive trials, the biological information is perceived
as meaningful only after a series of presentations, and here the role of
the system is not so crucial. Even amygdalectomized rats are capable
of multi-trial learning. However, AM-CG control is not excluded entirely.
What is decisive in the regulatory function of the AM-CG system?
Not its participation in the registration of reinforcement and not the
evaluation of the biological meaning of the information, although they
are important initial steps. The biologically meaningful ilnformatim has
to be retained in the brain after its first input. Consequently, the role
of the AM-CG system is a determinant in that it produces conditions
for the rapid fixation of a memory trace. Possibly, the activation of the
AM-CG system gives rise to two parallel processes, that is the appearance of emotions and the reorganization of the functional properties of
the neurons of other brain structures providing the rapid fixation of
a memory trace. However, it cannot be excluded that such a reorganization of the functional properties of neurons may be a coinsequence
of emotions.
To understand the role of emotiogenic brain structures in memory
control, we attempted to evaluate the relative contribution of each nuclear structure and to determine how the structures interact fmctimally.
We proceeded from the assumption that one-trial learning is one extreme
of the continuum of engram control. It so, the AM-CG system can
presumably regulate the fixation and retrieval of a memory trace in
a wide range from null to me-trial learning.
Therefore, repetitive pairings of conditioned and unconditioned stimuli (CS-US) can also be used to evaluate the contribution of the structures identified. For this purpose, M. Gilinsky and I. Pukhov (unpublished) used the conditioned evoked $potential (CEP) as suggested by
Adam (1). The CEP-method has been described in detail earlier (5).
The CEP, which is an electrographic manifestation of a memory trace
in brain structures, was compared with the conditioned neurographic
response of the motor nerve, a n effector component of the conditioned
response. It was impossible to establish any unambiguous functional relationship between the manifestation of the conditioned evoked potential and the conditioned neurographic response. For this reason, these
relationships were expressed as binary signs reduced to a common table.
This approach, developed in cooperation with the Computer Centre of
the Siberian Branch of the USSR Academy of Sciences (V. Drobishev,
T. Freidin, unpublished), permitted us to establish statistically the relationships between the manif estatims of the conditioned neurographic
response and the respective set of the CEP in various brain structures.
Quantitative estimates of the relative contribution of each brain
structure demonstrated that the appearance of the CEP in the z, incerta,
the preoptic area and the auditory cortex is most frequently accompanied by a conditioned neurographic response. This made necessary the
building of a matrix of the interaction of the various brain structures
Fig. 2. A matrix of the relationship between the distribution of the conditioned
evoked potential (CEP) and the neurographic response. The conditioned neurographic
response is constantly elicited when the CEP appears simultaneously in the ZI, the
APO and the AC. Black areas are those in which the CEP is distributed during the
registration of the neurographic response. Dashed areas indicate the expected area
of the neurographic response.
evoked conditioned response; -, no response.
+,
during the manifestation of the conditioned neurographic response (Fig. 2).
Analysis of this interaction indicated that the conditioned meurographic
response was a constant concomitant of the CEP in the zona incerta, the
preoptic area and the auditory cortex. The response also appeared, but
with much lower probability, when the CEP was elicited simultaneously
in various other combinations with the involvement of some of these
structures.
Taken collectively the analysis of data on the brain structures providing one-trial learning, the CEP probability of occurrence in these
structures and their correlation matrices, confirm that the AM-CG system
(the amygdaloid complex, the preoptic area, the zona incerta, the periand paraventricular nuclei of the hypothalamus, the midbrain central
gray) indeed controls memory. Ln the control of versatile memory processes, this system undoubtedly interacts with the thalarno-cortical and
other brain structures.
The AM-CG control system of the formation and retrieval of memory
trace was also made apparent in studies of the stimulation of the AM.
In experiments with immobilized cats, M. Gilinsky and I. Pukhov
(unpublished) showed that AM stimulation (60 pulsesls, pulse duration
oif 0.2 rns 3 V, stimulation for 3-5 min) before learning greatly accelerates it. Stimulated cats learned after 20-60 pairings of the CS-US
(Fig. 3); whereas nonlesioned cats required 120-300 pairings for acquisi-
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Fig. 3. Accelerated learning after amygdala stimulation in cats. The conditioned
evoked potentials after amygdala stimulation as the result of 20-60 pairings of CS
and US, as compared with 120-300 pairings in the control. A, habituation; B, 20
CS-US pairings after AM stimulation; C, testing after 20 min. Arrows indicate the
time when the CS-US were presented.
tion. Moreover, by artificially modifying the rhythm of the AM neurons,
one-trial learning was achieved in a situation requiring repetitive trials
for learning (3, 5). A similar effect was observed only when current
in the frequency range of 40-60 pulses/s was applied, that is when
a rhythm of burst electrical AM activity developed during emotional
tension (9, 10). It follows that the activation of one of the influential
structures of the system, the AM, greatly accelerates and facilitates the
formation of a memory trace.
A.n obvious question might now be asked: does the AM-CG system
participate in the control of memory trace retieval? M. Gilinsky, G. Abuladze, V. Masycheva and I. P u k h v (unpublished) studied the spatial
distribution of the CEP in brain structures and the retrieval of the
conditioned neurographic response after the stimulation of the AM and
the CG. The AM was stimulated (3-5 mi~ntrain of pulses, 0.2 ms duration
at 60 liHz, 3 V) or the CG (3-5 min train (of pulses, 0.1 ms duration a t
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Fig. 4. Facilitation of the retrieval of the conditioned responses by amygdala stimulation. When trained cats do not show conditioned response, AM stimulation facilitates the retrieval of the conditioned neurographic responses and CEP in the AC, the
ZI, the CG, the APO. A, habituation; B, 181 to 200 paired presentations; C, testing
promptly after 200 CS-US pairings; D, 30 min after AM stimulation. Arrows indicate the time when the CS-US were presented.
100 Hz, 3 V) only in the case when the first test after learning (100-200
CS-US pairings) diid not elicit the neurographic response. In the first
test for the CEP, the potential either did not appear at all or was restricted to one, two crr three brain structures. The conditioned neurographic
response appeared in 75O/o of caCs repetitively tested 20-30 min after
the AM stimulation. It is remarkable that the conditioned neurographic
response was registered simultaneously with the CEP in the auditory
cortex, the zona incerta and the preoptic area (Fig. 4). As already mentioned, this simultaneity is of decisive importance in the performance
of the behavioral response. Stimulation of the CG resulted in retrieval of
the conditioned neunographic respmse in 62.5OIo of cats; the CEP was
registe~edin the zma incerta, the preoptic area and, as a rule, in the
AM. Hence, the activation of the structures of the emotiogenic control
system of memory creates a spatial-temporal organization of brain structures that promotes the appearance of the effector conditioned response.
Through what mechanisms does the emotiogenic control system act
on memory? There are three lines of experimental evidence of relevance
to the understanding of the influence of emotiogenic structures on memory trace formation.
1. There is an increase in the number of cortical neurons with polysensory properties after AM stimulation (8). The enhancement of p l y sensory properties is characteristic of the acquisition of a conditioned
response under the effect of a biologically meaningful reinforcement (6).
However, the switching of converging mechanisms for the provision of
the interaction of stimuli is insufficient for their stable linkage (12).
2. The shortening of the autonomic residual r e s p s e s to an US
after amygdalwtomy, observed in the experiments of Volf and Tsvetovsky
(unpublished), may be evidence for the important role of the AM in
residual processes, especially in the retention of emotional responses. The
response of amygdalectomized animals to the direct action of stimuli is
retained. The involvement of the AM in the activation of convergence
and residual processes does testify to its significance in the control over
trace formation. However, the capacity for one-trial learning cannot
be explained by such an influence of the AM.
3. The most weighty line of evidence concerns inhibitory amygdalofugal influences. The capacity of inducing a rhythm of neuronal discharges in the AM for prolonging inhibition of impulse flow in the CG is
indicative of a modulating type of AM ilnfluence on the CG (2). Conceivably, the major influence of the emotiogeni~ccontrol system on memory
trace formation is to facilitate the emergence of a dominat focus and to
act on direct (lateral) and recurrent inhibition underlying interference.
Activating afferent flows exciting the structures of the emotiogenic control system arise during the stimulation of CG (where the affectivemotivational component of a n aversive stimulus are first perceived).
According to the data of Dubrovina, 86O/0 of reactive neurons of the zosa
incerta are excited during CG stimulation (Fig. 5).
It may be thought that the delivery of emotionally colored information activates the CG, the initial component of the system which modulates affective behavior. This activation may spread over to other
nuclei of the emotiogenic control system (those of the AM, the zona
incerta, the peri- and paraventricular nuclei of the hypothalamus). This
activation of the entire emotiogenic control system can provide conditions
for the dominant determining of the activity of the neuronal centers
at a particular point in time. A dominant focus itself is one of the initial
steps of the elaboration of conditioned responses as demonstrated by
Rusinov (13). There are also data (6) indicatirng that the dominant state
produced by a biologically meaningful reinforcement is of importance
in the rate of meurmal activity reorganization of a signal type and in
the maintenance of established relationships.
Subsequent amygdalofugal inhibition may maintain the dominant
state. Stimulation of the AM inhibited 72O/o of reactive neurons in the
Fig. 5. Neuronal activity in the amygdaloid complex - midbrain central gray matter
system. The CG has predominantly a n excitatory ascending effect on the ZI neurons
(A), whereas the AM has an inhibitory effect on the neurons of the ZI (B)and the
CG (C).
Fig. 6. Functional relationships in the amygdaloid complex - the midbrain central
gray matter system. Convergence of inhibitory i~nfluencesdescending from the AM
(1) and of excitatory influences ascending from the CG (2) a t the ZI neurons. Convergence of predominantly inhibitory influences descending from the AM (3) and
the ZI (4) a t the CG neurons.
CG and 64O/o of those in the z. incerta (Fig. 5). It is noteworthy that
impulses from the AM and the zona incerta have predominantly an
inhibitory effect (71°/o) on the same CG neurons (Fig. 6); convergence
of excitative impulses was observed only in 20°/o of neurons (2). As to
mna incerta, 57O/o of the neurons show an inhibitory response to the
influence of the AM and an excitatory one to that of the CG; 30°/o of its
neurons respond only by excitation to the influences of either the AM
or the CG.
Possibly, after the registration of biologically meaningful information,
which was evaluated earlier at the level of the CG and the AM,amygdalofugal influences inhibit the structures of the emotiogenic control system. The emerging pattern of retroactive and proactive ifnhilbition may
facilitate the formation of a dominant, thereby promoting the fixation
of a single information input. Rapid and secure fixation of a trace and
its linkage with the established retrieval program are provided by the
weakening of the effects of preceding traces by retroactive inhibition,
the enhancement of the dominant and the weakening of the interfering
effects of subsequent emotionally colored sensory input by proactive inhibition.
However, the feasibility of subsequent trace formation after different
time intervals depends on whether the trace is readable, but not an
how it is fixed (short- or long-term memory). Interference may be m e
of the causes of the rapid passage of a fixed trace to a subthreshold state
which impedes its retrieval; this is outwardly seeming short-term memory. This memory is short for the only reason that its trace has become
subthreshold and difficult to retrieve. One is confronted here not with
the disappearance of a short-term memory trace, but rather with its
rapid passage to a subthreshold level. Many factors may be causative:
retroactive inhibition due to interference of subsequent signals, insufficient reinforcement, attention concentration, general setting and emotional concomitants, among others. The presentation of a single stimulus,
without emotions is promptly followed by a sort of information loss,
forgetting.
These time intervals of trace retention can be subdivided into shorter
ones. We can thus obtain transient, ultrashort and other "versions" of
memory, which explains why the so-called short term memory lasts
from 10 s to several hours according to data iln the literature.
In multi-trial learning, the biological meaning of a neutral stimulus
becomes apparent only after its repeated pairings with reinforcement.
The production of a dominant is facilitated by the summation of incoming stimuli. Each subsequent stimulus can reinforce the !preestablished
trace making it more stable. This may promote the maintenance of a trace
10
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Neurobiol. Exp. 6179
at a threshold level in which it remains readable for a long time, that
is one is confronted here with long-term memory.
Long retention of a memory trace is also possible in one-trial learning, provided that information input was emotionally associated. The
activation of the emotiogenic control system of memory at the time of
me-trial learning may result in stronger retroactive inhibition attenuat b g the effects of the preceding traces. This may promote the rise of
a new dominant. In turn, the promoted dominant helps the trace to
remain superthreshold longer in the structures of this emotiogenic system. Thus, conditions may arise favorable for subsequent retrieval. One
of these major conditions is the m t a n t availability of a memory trace
in the structures of the emotiogenic control system.
The trace of emotional memory is not erased, nor is it subjected to
amnesia (5). The subsequent emotions activate these traces making them
easier to read in the emotiogenic structures, and, as a result, the whole
adaptive program, preestablished and trace-linked in these structures, is
efficiently retrieved.
REFERENCES
1. ADAM, G. 1987. Interoception and behaviour. Acad., Kiado, Budapest.
2. DUBROVINA, N. I. and ILYUTCHENOK, R. Yu. 1978. Neuronal activity of
midbrain central gray substance under amygdaloid and subthalamical stimulation (in Russian). Neurophysiologiya 3: 245-251.
3. GOLD, P. E., HANKINS, L., EDWARDS, R. M., CHESTER, J. and McGAUGH,
J. L. 1975. Memory interference and facilitation with posttrial amygdala
stimulation effect on memory varies with footshock level. Brain Res. 86:
509-513.
e
4. HILTON, S. M. and ZBROZYNA, A. W. 1963. Amygdaloid region for defence
reactions and its efferent pathway to the brain stem. J. Physiol. (Lond.)
165: 160-173.
5. ILYUTCHENOK, R. Yu., VINNITSKY, I. M. and LOSKUTOVA, L: W. 1977.
Neirokhimicheskie mekhanizmy mozga i pamyat'. Izdat. Nauka, Novosibirsk.
6. KOTLYAR, B. I. 1977. Mekhanizmy formirovanija vremennoi' svyazi: Izdat.
Gosud. Moscow Univ., Moscow.
7. LIEBMAN, J. M., MAYER, F. J. and LIEBESKIND, J. C. 1970. Mesencephalic
central gray lesions and fear-motivated behavior in rats. Brain R e . 23:
353-370.
8. MAKAROV, V. A. 1970. The role played by the amygdala in the mechanism
of convergence of stimulations of different sensory modality on the neurons
of the large hemisphere cortex (in Russian). Rep. Acad. Sci. Ukr. SSR. 194,
6 : 1454-1457.
9. McLENNAN, H. and CRAYSTONE, P. 1965. The electrical activity of
the
amygdala and its relationship to that of the olfactory bulb. Can. J. Physiol.
Pharmacol. 43: 1009-1017.
10. ONIANI, T. N. and ORJONIKIDZE, Ts. A. 1968. Changes in electrical activity
of some brain structures of the cat during general behavioural reactions. In
Contemporary problems of activity and structure of the central nervous
system. Mezniereba, Tbilisi, p. 5-13.
11. PELLEGRINO, L. 1968. Amygdaloid lesions and behavioral inhibition in the
rat. J. Comp. Physiol. Psychol. 65: 483491.
12. RABINOVICH, M. Ya. 1975. Zamykatelnaya funktsiya mozga. Izdat. Meditsina,
Moscow.
13. RUSINOV, V. S. 1969. Dominanta. Medicine, Moscow.
14. VINNITSKY, I. M. and ILYUTCHENOK, R. Yu. 1973. Elaboration of defensive
conditioned reflexes in amygdalectomized rats. Zh. Vyssh. Nervn. Deyat.
Im. I. P. Pavlova 23, 4: 766-770.
R . Yu. ILYUTCHENOK, Institute of Physiology, Siberian Branch of the Academy of Medical
Sciences of the USSR, Zolotodolinskaya 101, 630090 Novosibirsk, USSR.
LIST OF ABBREVIATIONS
AC
auditory cortex
AHA
anterior hypothalamic area
AM
amygdaloid complex
preoptic area
APO
bed n. Str. t. bed nucleus of the stria terminalis
diagonal band of Broca
Br
bulbus olfactorius
Bulb. olf.
midbrain central gray matter
CG
peri- and paraventricular nuclei of the hypothalamus
HPV
medial forebrain bundle
MFB
midbrain reticular formation
RT
stria terminalis
ST
nucleus ventralis anterior
VA
ventral amygdalofugal pathway
VAF
ventromedial hypothalamus
Vm
zona incerta
ZI