Brain Research 888 2001 34–50 www.elsevier.com locate bres
Research report
Visual discrimination learning impairments produced by combined transections of the anterior temporal stem, amygdala and fornix in
marmoset monkeys
a b
a , a
Catherine J. Maclean , David Gaffan , Harry F. Baker , Rosalind M. Ridley
a
Department of Experimental Psychology , Downing Street, Cambridge CB2 3EB, UK
b
Department of Experimental Psychology , South Parks Road, Oxford OX1 3UD, UK
Accepted 19 September 2000
Abstract
Marmoset monkeys Callithrix jacchus with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to
relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicating that they had a dense retrograde amnesia. They also had
difficulty learning new visual object discriminations but were only mildly impaired on spatial learning. When tested on new learning of concurrent discriminations 8 to 10 weeks after surgery, three operated monkeys were unable to reach criterion in 400 trials while the
remaining two operated monkeys performed within the normal range. The operated monkeys were subsequently shown to be impaired on acquisition of shape discriminations using black objects. These anterograde effects suggest that the impairment runs mainly in the domain
¨ of visual analysis. The monkeys also exhibited many of the features of the Kluver–Bucy syndrome. Histological analysis indicated that in
addition to cutting some of the subcortical temporal lobe efferent pathways, the surgical procedures had cut the cholinergic afferents to the temporal neocortex, entorhinal cortex, and hippocampus. In a second experiment we found that treatment with the cholinergic agonist
pilocarpine, which is effective in monkeys with specific cholinergic lesions, was unable to remediate the lesion-induced impairments. This suggests that transection of the non-cholinergic afferents, or the temporal lobe subcortical efferents, contributed to the behavioural
syndrome and the learning and retention deficits seen in these monkeys.
2001 Elsevier Science B.V. All rights reserved.
Theme : Neural basis of behavior
Topic : Learning and memory systems and functions – animals
Keywords : Temporal stem; Amygdala; Fornix; Discrimination learning; Monkey
1. Introduction nisms originating in other brain areas. Some of the efferent
projections carrying information processed in the ‘ventral In order that behavioural choices can be made in
stream’ of the visual association cortex leave the temporal response to visual perceptions it is essential that infor-
lobe via the temporal stem [43,59], and the fornix [45]. mation processed in the visual association areas of the
Subcortical nuclei send afferent projections through the temporal lobe should escape to other brain areas and that
temporal stem, amygdala and fornix into the temporal visual processing in the temporal lobes should be under the
lobes [55,61] and these inputs may influence the way in influence of attentional, motivational and hedonic mecha-
which visual information is processed. A wide variety of lesions within the ‘ventral stream’,
including transections of the temporal stem, amygdala and fornix, produce impairment on tasks which require the
Corresponding author. Innes Building, School of Veterinary Medicine,
perception, identification, and recognition of objects.
Madingley Road, Cambridge CB3 0ES, UK. Tel.: 144-1223-339-015;
Macaques with transection of the anterior temporal stem
fax: 144-1223-339-014. E-mail address
: hfb22cam.ac.uk H.F. Baker.
are impaired on retention and new learning of pattern
0006-8993 01 – see front matter
2001 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 9 9 8 - X
C .J. Maclean et al. Brain Research 888 2001 34 –50
35
discriminations [28,63,65] and on performance of ‘recogni- stream from the subcortical afferents which provide the
tion’ tasks [11]. Macaques with suction ablations of the modulatory control of visual processing.
amygdala are severely impaired at learning certain types of These subcortical afferent systems include the rising
reward-association tasks [17], although macaques with cholinergic projections of the basal forebrain which project
axon-sparing, excitotoxic lesions of the amygdala may be most heavily into the temporal and frontal lobes. Choliner-
less affected [36]. This suggests that fibres passing through gic cells in the basal nucleus of Meynert NBM project,
the amygdala may be crucial for certain types of learning. via the temporal stem, to and through the amygdala, and
Fornix transection causes a severe impairment on tasks to the inferotemporal and perirhinal cortex [55]. Choliner-
requiring memory for real scenes [14] or items in fixed gic cells in the vertical limb of the diagonal band VDB
spatial arrays [15] and a mild impairment on performance project to the main body of the hippocampus and the
of ‘recognition’ tasks [13]. None of these lesions, however, entorhinal cortex via the fornix [3] and the supracallosal
produce impairments which appear to match the sort of stria
of Lancisi
personal observation
while some
catastrophic amnesia which can occur in humans with cholinergic projections reach the anterior hippocampus and
substantial temporal lobe damage, e.g., [62]. adjacent entorhinal cortex via the temporal stem [32].
Patients with amnesias of various aetiologies have There have been only limited attempts, using excitotox-
difficulty in performing ‘recognition’ tasks [1,41,56] and in ins, to produce lesions of these projections in macaques
learning visual discriminations presented concurrently [60] although more complete lesions have been produced
[1,20,24,42]. Although the precise cognitive requirement by immunotoxic methods in marmoset monkeys. Immuno-
for performance of these tasks is open to question, an toxic lesions of the cholinergic cells of the NBM1VDB
understanding of the neuroanatomical substrate of per- produce a severe and persistent impairment on object
formance of these tasks is pertinent to understanding discrimination learning in marmosets [47,50]. Lesions
amnesia. A critical area for ‘recognition’ performance is confined to the NBM produce smaller, transient effects on
the perirhinal cortex [9,37] and impairments on slightly visual discrimination learning and retention [12,47,50]
modified versions of concurrent discrimination learning while lesions of the VDB produce large, persistent impair-
have also been found following ablations confined to ments confined to certain types of conditional learning
perirhinal cortex [6–8]. The inferotemporal cortex has also [50]. That these lesions have these cognitive effects
been implicated in performance of ‘recognition’ tasks [39] because they deprive the temporal lobe of modulatory
and concurrent discrimination learning [29]; see also [10] support is demonstrated by the impairments which follow
for a retrospective analysis of work done in one laboratory. crossed unilateral lesions of the NBM VDB and in-
This suggests that, notwithstanding the evidence in favour ferotemporal cortex and hippocampus [5]. Since the trans-
of the role of the medial temporal lobe structures in ections of the anterior temporal stem, amygdala and fornix
memory, some temporal neocortex comprising at least performed in macaques by Gaffan et al. [19] destroy the
inferotemporal and perirhinal cortex also makes a substan- cholinergic afferents to the temporal lobe from the NBM
tial contribution to memory functions. and the VDB, respectively, it seemed appropriate to
Patients with large medial temporal lobe lesions e.g., explore the effects of this lesion in marmosets as well as
[31,54] exhibit a much denser amnesia than do patients macaques. Learning impairments which were the conse-
with fornix transection [16] or damage restricted largely to quence solely of the loss of these afferents might be
the hippocampus [46]. Monkeys with large temporal lobe ameliorated by cholinergic agonists since this treatment
lesions e.g., [38–40,64] also exhibit denser impairments has been found to be effective in monkeys with fornix
than do those with smaller medial temporal lobe lesions transections [52] or NBM and or VDB lesions [49–51].
[66] or fornix transection [13]. Horel [25] appreciated the A further behavioural feature worthy of comparison
importance of the temporal neocortex in memory forma- between macaques and marmosets is the occurrence of the
¨ tion and argued that much experimental and clinical data
Kluver–Bucy syndrome. Bilateral temporal lobectomy in ¨
apparently implicating the medial temporal lobe structures, macaques produces the Kluver–Bucy syndrome which
especially the hippocampus, in memory formation could be comprises ‘psychic blindness’, and inappropriate emotional
interpreted as demonstrating an involvement of the tempo- and appetitive responses to visual stimuli [33]. Many of
¨ ral stem. Gaffan et al. [19] have recently demonstrated a
the signs of the Kluver–Bucy syndrome have been seen in very dense amnesic syndrome in macaques with combined
macaques with transections of the temporal stem [28], or transection of the anterior temporal stem, amygdala and
following amygdalectomy [22,27,30] or inferotemporal fornix. Macaques with this combination of lesions were
cortical ablation [2,27,30]. Horel showed that signs of the ¨
more severely impaired on the object-in-place task and the Kluver–Bucy syndrome could also be produced by pre-
delayed matching-to-sample task than were macaques with venting visual input into the temporal lobe by making
only some of these lesions. Macaques with all three lesions crossed unilateral lesions of the striate cortex and in-
were also severely impaired on concurrent discrimination ferotemporal cortex together with a transection of the
learning. Gaffan et al. [19] argue that this severe impair- posterior corpus callosum [26]. We have recently observed
¨ ment arises mainly because of disconnection of the ventral
the Kluver–Bucy syndrome and severe learning impair-
36 C
ments in marmosets with ablations confined to the in- matched for learning ability on the basis of performance on
ferotemporal cortex [53]. Marmosets with lesions of the these tasks. Monkeys from the two sources named above
NBM1VDB or fornix transection alone show learning were distributed between the two new groups. Monkeys in
¨ impairments
but not
the Kluver–Bucy
syndrome Group C2 n54 were unoperated and monkeys in Group
¨ [47,48,50,52].
The occurrence
of the
Kluver–Bucy L2 n54 had the same surgical procedure as monkeys in
syndrome in marmosets with transection of the anterior Group L1.
temporal stem, amygdala and fornix would therefore be unlikely to be just a consequence of impaired visual
2.2. Surgery discrimination learning ability.
Some authors have considered the symptoms of the For surgery, each monkey was premedicated with 0.05
¨ Kluver–Bucy syndrome in macaques to be the behavioural
ml ketamine 100 mg ml, i.m., Vetalar, Pharmacia, Lux- manifestation of visual agnosia, i.e., a gross impairment of
embourg and anaesthetised with 18 mg kg alphaxolone– visual analysis [21,33]. Although macaques with small
alphadolone i.m., Saffan, Schering-Plough, Welwyn Gar- ¨
inferotemporal lesions do not exhibit florid Kluver–Bucy den City, UK. Dexamethasone 2 mg kg, i.m., Merck,
signs, it has been argued that their learning impairment Sharpe and Dohme, Harlow, UK was given just before
also arises from some sort of difficulty with visual analysis surgery, to limit cerebral oedema. Each monkey was
rather than from a memory impairment per se [18]. It is placed in a stereotaxic frame and, following incision of the
therefore pertinent to ask whether the behavioural dis- skin and retraction of the temporal muscles, a large cranial
turbance and or the learning impairment seen after trans- flap was removed to allow a clear view of the dorsal and
ection of the anterior temporal stem, amygdala, and fornix lateral surfaces of the brain. A large stellate incision was
could also be attributed to difficulties in visual analysis. made in the dura mater over the surface of one hemisphere
and the dural flaps retracted. A small hole was made by suction through the corpus callosum between the hemi-
2. Materials and methods spheres at co-ordinates AP 17.0 to 18.0 mm [57]. The
