Research reportDistinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat
Introduction
The hippocampus — a region known to have a critical role in certain types of learning and memory — communicates with other brain regions via two major pathways: (i) connections via the fornix and (ii) connections via parahippocampal regions such as the perirhinal and postrhinal cortices. The former pathway not only contains subcortical and cortical projections from the hippocampus, but also conveys afferents to the hippocampus, including those from the septum [25], [39]. The parahippocampal pathway is thought to be a major source of afferent sensory information [6], which is conveyed to the hippocampus from the perirhinal/postrhinal cortex via the entorhinal cortex [6], [38]. In addition to this indirect route via the entorhinal cortex, there may also be direct projections from the perirhinal/postrhinal cortex to the hippocampus [45]. This tight interconnectivity has provided the foundation for theories that emphasize a unitary memory system comprising these various regions [14], [37].
It is perhaps surprising, then, that lesions of the fornix or of parahippocampal cortical regions do not always have equivalent effects, and do not always mimic the effects of hippocampal lesions. Indeed, in one study that compared directly the effects of fornix lesions and perirhinal cortex lesions in rats, a double dissociation was obtained [17]. While fornix lesions severely disrupted performance on two spatial tasks that are also sensitive to hippocampal damage (T-maze alternation and delayed nonmatching-to-position in an operant chamber), the same fornix lesions had no effect on a spontaneous test of object recognition. In contrast, perirhinal cortex lesions resulted in a recognition deficit but had no effect on the spatial tasks.
All other comparisons between the effects of such lesions in rats have been indirect, as only one or the other of the two sites has been examined in a given study. While a comparison of these studies does support this dissociation on tests of object recognition [3], [8], [31], the results from spatial tasks have been less consistent, as some studies have reported deficits after perirhinal cortex damage [3], [8], [15], [23], [26], [27], [28], [29], [42], [43].
In view of the inherent limitations of such indirect comparisons and the potential importance of these dissociations for understanding the functions of the hippocampus and related structures, the present study sought to compare directly the effects of these different hippocampal disconnections on object recognition and spatial memory tasks. Unlike the study of Ennaceur et al. [17], we extended the perirhinal cortex lesions caudally to include the postrhinal cortex and dorsally to include area TE. This was for two reasons. First, by sparing the postrhinal cortex the study of Ennaceur et al. [17] had left a route by which spatial information could reach the hippocampus and this might explain the lack of any apparent effect on tests of spatial memory. Second, by extending the cortical lesion dorsally it might be expected that a more robust recognition deficit would emerge, so further testing the reported dissociation.
Although our prediction was that the effects of fornix and perirhinal/postrhinal cortex lesions would be dissociable, such a finding would not rule out the possibility that these lesions could have similar effects under certain conditions in which, for example, the hippocampus and perirhinal/postrhinal cortex interact, i.e. in situations where object and spatial information must be integrated. This was tested using two very different paradigms having both ‘object’ and ‘spatial’ characteristics. The first was an ‘object-in-place’ test, carried out in the same apparatus and with the same stimulus material as the object recognition test. Unlike the object recognition test, however, in the object-in-place test rats recognise not that a specific object has been seen before, but that a specific object has exchanged position with another specific object. We also tested these animals on an ‘object location’ test in which rats recognise that an object is in a place that had not previously been occupied by any object; thus this task requires the use of spatial information only.
The second object/place task we examined was a visuospatial conditional learning task, carried out in a computerised touchscreen apparatus [11], in which rats must learn a rule of the type: ‘If stimulus A go left; if B go right’. Both fornix and hippocampal lesions have been reported to disrupt visuospatial conditional discrimination [34], [36], [40], and it has been suggested that impairments on such tasks may result from inadvertant damage to perirhinal cortex [34]. Furthermore both the hippocampus and the perihinal/postrhinal cortex are connected with the posterior cingulate cortex, which has been shown to be necessary for normal acquisition of visuospatial conditional tasks [9], [10]. In order to ensure that lesioned rats could discriminate nonspatial and spatial computer graphic stimuli in this apparatus, we first tested the rats on two additional touchscreen tasks: stimulus–reward learning in a discriminative Pavlovian autoshaping paradigm [7], and a pattern discrimination learning task using equiluminant shape stimuli. An additional motivation for using these particular tasks is that the results could help to clarify whether the perirhinal/postrhinal region is important for any particular class of learning and memory task, or whether it is specialised for the processing of particular stimulus material.
Section snippets
Subjects
The study involved 36 naive, male rats of the pigmented DA strain (Bantin and Kingman, Hull, UK). Throughout the period of the experiment the rats were housed in pairs under diurnal conditions (14 h light/10 h dark). At the time of surgery they were aged around four months and weighed between 210 and 270 g. All animals were given a minimum of 2 weeks to recover from surgery before the first test (object recognition) began. For some of the postoperative test period the animals were placed on a
Experiment 1
Experiment 1 compared the effects of fornix transection and excitotoxic lesions of the perirhinal/postrhinal cortex on object recognition and spatial memory tasks. The object recognition task was the same as that used previously [16], [17], in which rats recognise that an object has been encountered previously. Spatial memory was examined in a delayed alternation task carried out in a T-maze.
Apparatus
The apparatus consisted of an open arena (100×100×46 cm) made of wood, the inside of which was painted grey. The floor was covered with sawdust. The arena was situated in a room containing features such as a door, light fixtures and a video camera, and a large dark screen which served to conceal the experimenter. Triplicate copies were obtained of the objects to be discriminated, which were made either of glass, plastic or metal. For any given test the pairs of objects to be discriminated were
Histological analysis
The PPRH lesions consistently removed almost all of the perirhinal and postrhinal cortex. The rostral limit of the lesions was level with the rostral third of the amygdala while caudally the lesions often extended to the most posterior portions of the postrhinal cortex (Fig. 2). Within the extent of the lesion there was essentially no evidence of neuronal sparing, although in two cases there was some unilateral sparing of deeper cortical layers at the junction of the postrhinal and perirhinal
Experiment 2
In experiment 1, it was found that lesions of the fornix and of the perirhinal/postrhinal cortex led to distinct patterns of behavioural impairments. It was found that in general, lesions of the fornix impaired spatial memory, whereas lesions of the perirhinal/postrhinal cortex impaired object recognition. In experiment 2 we sought to investigate whether these lesions would have more similar effects under conditions in which the hippocampus and perirhinal/postrhinal cortex might interact, i.e.
Object location test
The apparatus and general procedure for both the object-in-place and object location tests was the same as that in experiment 1. Unlike the object recognition test, rats were not tested on the ability to distinguish between objects or to make judgements based on the familiarity of objects. Instead, normal discrimination involved rats recognising that an object had changed location (Fig. 1B). The use of information about the specific identity of the object was thus not required. Two copies of
Exploration during sample period
In this procedure the sample period was held constant at 3 min, and the amount of time spent exploring the objects during that time was recorded and analysed. There was a significant main effect of group, F(2,30)=5.10, P<0.05. Post-hoc Newman–Keuls analysis revealed that animals of the FNX group spent more time exploring the objects during the sample phase than animals of either the CONT or PPRH groups (both P<0.05; MEANS: CONT=13.0; FNX=16.5; PPRH=13.2 s).
Recognition during test period
The analyses took the same form as
Experiment 3
In experiment 2 evidence was found that in certain situations contributions from the fornix and perirhinal/postrhinal cortex may be integrated. In the object-in-place test PPRH animals failed according to two measures, and FNX animals failed according to one measure, to discriminate objects that remained fixed in place, with those that had exchanged locations with other objects (see Table 1). In experiment 3 we examined a second type of task in which object and place information may need to be
Apparatus
Testing was conducted in an automated apparatus in which a computer video display unit (VDU) presented stimuli to the animal [11]. The VDU was attached to a touch screen so that the animals could select computer produced stimuli by directly responding toward the VDU with their noses. This apparatus was housed within a wooden sound-attenuating box. The inner chamber measured 48×30×30 cm, and consisted of a metal frame, clear Perspex walls, and an aluminium floor. Located centrally on the wall at
Discriminated approach
Difference scores (approaches to the CS+ minus approaches to the CS−) were analysed across the ten blocks of ten stimulus presentations. There was a significant effect of group, F(2,30)=3.76, P=0.035, but no group×block interaction, F(18,270)=1.03, P=0.42. Newman–Keuls post-hoc analysis revealed that the group effect was due to animals of the PPRH group attaining higher levels of discrimination performance than either of the FNX or CONT groups (both P<0.05). There was, however, a significant
Discussion
A major aim of the present study was to compare directly the effects of two different disconnections of the hippocampus — fornix transection and excitotoxic lesions of the perirhinal and postrhinal cortices — on tests of object and spatial memory. The two lesions led to distinct patterns of behavioural impairments. Perhaps the most clear comparison was between the object recognition and allocentric T-maze alternation tasks (experiment 1). Animals with perirhinal/postrhinal cortex lesions (PPRH)
Acknowledgements
This research was supported by a project grant from the Wellcome Trust. The authors thank Alison Baird and Angie Morgan for invaluable assistance with behavioural testing and histology.
References (45)
- et al.
The effects of hippocampal lesions upon spatial and non-spatial tests of working memory
Behav. Brain Res.
(1986) - et al.
Extensive cytotoxic lesions involving both the rhinal cortices and area TE impair recognition but spare spatial alternation in the rat
Brain Res. Bull.
(1997) Spatial learning and memory processes: the search for their neurobiological mechanisms in the rat
Trends Neurosci.
(1988)- et al.
Dissociable effects of anterior and posterior cingulate cortex lesions on the acquisition of a conditional visual discrimination: facilitation of early learning vs. impairment of late learning
Behav. Brain Res.
(1996) - et al.
Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition
Behav. Brain Res.
(1999) - et al.
The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat
Behav. Brain Res.
(1997) - et al.
Neurotoxic lesions of the perirhinal cortex do not mimic the behavioural effects of fornix transection in the rat
Behav. Brain Res.
(1996) - et al.
Inferotemporal-frontal disconnection and fornix transection in visuomotor conditional learning by monkeys
Behav. Brain Res.
(1988) - et al.
Comparison between the behavioural effects of septal and hippocampal lesions: a review
Neurosci. Biobehav. Rev.
(1983) - et al.
Perceptual-mnemonic functions of perirhinal cortex
Trends Cogn. Sci.
(1999)
The anatomy, physiology and functions of the perirhinal cortex
Curr. Opin. Neurobiol.
The effects of perirhinal cortical lesions on spatial reference memory in the rat
Behav. Brain Res.
Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region
Prog. Neurobiol.
Episodic memory, amnesia, and the hippocampal-anterior thalamic axis
Brain Behav. Sci.
Perirhinal cortex ablation impairs visual object identification
J. Neurosci.
Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature and comparison with findings from the monkey brain
Hippocampus
Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: implications for the neurobiology of emotion
Behav. Neurosci.
Functionally dissociating aspects of event memory: the effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat
J. Neurosci.
Triple dissociation of anterior cingulate, posterior cingulate, and medial frontal cortices on visual discrimination tasks using a touchscreen testing procedure for the rat
Behav. Neurosci.
A novel automated touchscreen procedure for assessing learning in the rat using computer graphic stimuli
Neurosci. Res. Commun.
Fornix lesions can facilitate acquisition of the transverse patterning task: a challenge for ‘configural’ theories of hippocampal function
J. Neurosci.
Two functional components of the hippocampal memory system
Behav. Brain Sci.
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