Spatial and non-spatial learning in turtles: the role of medial cortex

In mammals and birds, hippocampal processing is crucial for allocentric spatial learning. In these vertebrate groups, lesions to the hippocampal formation produce selective impairments in spatial tasks that require the encoding of relationships among environmental features, but not in tasks that require the approach to a single cue or simple non-spatial discriminations. In reptiles, a great deal of anatomical evidence indicates that the medial cortex (MC) could be homologous to the hippocampus of mammals and birds; however, few studies have examined the functional role of this structure in relation to learning and memory processes. The aim of this work was to study how the MC lesions affect spatial strategies. Results of Experiment 1 showed that the MC lesion impaired the performance in animals pre-operatively trained in a place task, and although these animals were able to learn the same task after surgery, probe test revealed that learning strategies used by MC lesioned turtles were different to that observed in sham animals. Experiment 2 showed that the MC lesion did not impair the retention of the pre-operatively learned task when a single intramaze visual cue identified the goal. These results suggest that the reptilian MC and hippocampus of mammals and birds function in quite similar ways, not only in relation to those spatial functions that are impaired, but also in relation to those learning processes that are not affected.     

Telencephalon and geometric space in goldfish

Neuroanatomical evidence indicates that the lateral pallium (LP) of ray-finned fishes could be homologous to the hippocampus of mammals and birds. Recent studies have found that hippocampus of mammals and birds is critical for learning geometric properties of space. In this work, we studied the effects of lesions to the lateral pallium of goldfish on the encoding of geometric spatial information. Goldfish with telencephalic lesions were trained to search for a goal in a rectangular-shaped arena containing one different wall that served as the only distinctive environmental feature. Although fish with lateral pallium lesions learned the task even faster than sham and medial pallium (MP)-lesioned animals, subsequent probe trials showed that they were insensitive to geometric information. Sham and medial pallium-lesioned animals could use both geometric and feature information to locate the goal. By contrast, fish with lateral palium lesions relied exclusively on the feature information provided by the wall of a different colour. These results indicate that lesions to the lateral pallium of goldfish, like hippocampal lesions in mammals and birds, selectively impair the encoding of geometric spatial information of environmental space. Thus, the forebrain structures of teleost fish that are neuroanatomically equivalent to the mammalian and avian hippocampus also share a central role in supporting spatial cognition. Present results suggest that the presence of a hippocampal-dependent memory system implicated in the processing of geometric spatial information is an ancient feature of the vertebrate forebrain that has been conserved during the divergent evolution of different vertebrate groups.     

Relative medial and dorsal cortex volume in relation to foraging ecology in congeneric lizards

The need to locate distributed resources such as mates, food, and nests is correlated with an enlarged hippocampus in many mammalian and avian species. This correlation is believed to be a consequence of selection for spatial ability. Little is known about how such ecological needs affect non-mammalian, non-avian species. In lizards, the putative hippocampal homologues are the dorsal cortex (DC) and medial cortex (MC). We examined the relationship between foraging ecology and the size of the DC and MC in congeneric male lizards. We predicted based on the mammalian and avian literature that Acanthodactylus boskianus, an active forager that captures clumped, immobile prey would have a larger MC and DC than A. scutellatus, a sit-and-wait predator, that captures mobile prey. Our previous behavioral studies showed that A. boskianus did not differ from A. scutellatus on a spatial task but that A. boskianus was significantly better at the reversal of a visual discrimination, another task that is hippocampally dependent in mammals. In the current study, we found that, relative to telencephalon volume, the MC and DC were larger in the active forager whereas a control region, the lateral, olfactory, cortex, was similar in size between species. The current anatomical results suggest that MC and DC size is related to active foraging in lizards and, along with our previous behavioral studies, show that it is possible for this relationship to occur in the absence of evidence for species differences in spatial memory. Copyright (R) 2000 S.Karger AG, Basel     

Perirhinal cortex involvement in allocentric spatial learning in the rat: Evidence from doubly marked tasks

It has recently been suggested that the different cortices of the medial temporal lobe support a mixture of object and spatial processing functions, challenging the anterior model that emphasized a strict functional differentiation between regions. However, for some structures, the perirhinal cortex (Prh) for example, a number of studies using lesion methods have shown a profound deficit exclusively in tasks involving object learning but not allocentric spatial learning. It may be that the learning paradigms used in previous studies have not been sensitive enough to detect a possible allocentric deficit in Prh‐lesioned animals. To examine whether Prh lesions critically affect allocentric spatial learning, experimental and control rats were trained in two doubly marked navigation tasks. In experiment 1, the use of either one of two different memory systems, allocentric versus egocentric, made it possible to locate the goal arm in a four‐arm radial maze. In experiment 2, rats had to choose between an allocentric versus a S‐R/habit strategy, both of which predicted the location of the goal arm. Results showed that both experimental and control animals learned both navigation tasks well, reaching the same level of performance at the end of training. However, a probe test performed 1 day after the learning ended revealed that Prh‐damaged animals learned both tasks predominantly using a non‐allocentric strategy. Specifically, in lesioned subjects the percentage of egocentric correct responses (experiment 1) and the percentage of habit‐based correct responses (experiment 2) was significantly higher than in the control rats. On the other hand, in both experiments, control rats in the probe test presented a significantly higher number of allocentric correct responses than the lesioned subjects. These results clearly suggest that Prh is normally needed for using allocentric strategies in order to solve a navigation problem. © 2017 Wiley Periodicals, Inc.     

Relative medial and dorsal cortex volume in relation to sex differences in spatial ecology of a snake population

In non-avian reptiles the medial and dorsal cortices are putative homologues of the hippocampal formation in mammals and birds. Studies on mammals and birds commonly report neuro-ecological correlations between hippocampal volume and aspects of spatial ecology. We examined the relationship between putative homologous cortical volumes and spatial use in a population of the squamate reptile, Agkistrodon piscivorus, that exhibits sex differences in spatial use. Do male A. piscivorus that inhabit larger home ranges than females also have larger putative hippocampal volumes? Male and female brains were sectioned and digitized to quantify regional cortical volumes. Although sex differences in dorsal cortex volume were not observed, males had a significantly larger medial cortex relative to telencephalon volume. Similar to studies on mammals and birds, relative hippocampal or medial cortex volume was positively correlated with patterns of spatial use. We demonstrate volumetric sex differences within a reptilian putative hippocampal homologue.     

Is the avian hippocampus a functional homologue of the mammalian hippocampus?

The effects of hippocampal lesions on the processing and retention of visual and spatial information in birds and mammals is reviewed. Both birds and mammals with damage to the hippocampus are severely impaired on a variety of spatial tasks, such as navigation, maze learning, and the retention of spatial information. In contrast, both birds and mammals with damage to the hippocampus are not impaired on a variety of visual tasks, such as delayed matching-to-sample, concurrent discrimination, or retention of a visual discrimination. In addition, both birds and mammals with hippocampal damage display impairments in the acquisition of an autoshaped response, as well as alterations in response suppression. These findings suggest that the avian hippocampus is a functional homologue of the mammalian hippocampus, and that in both birds and mammals the hippocampus is important for the processing and retention of spatial, rather than purely visual information.     

Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis

The role of forebrain cholinergic projections in place navigation learning was assessed in two experiments. Following surgery, rats were required to learn the spatial location of an underwater platform on the basis of distal room cues. Bilateral injections of ibotenic acid into the nucleus basalis magnocellularis depleted choline acetyltransferase (ChAT) from the anterior and temporoparietal cortex but not the hippocampus. Separate histological studies confirmed the accuracy of the lesions and demonstrated a marked loss of cortical acetylcholinesterase. These rats subsequently showed no deficits in spatial learning or memory. In a second experiment, bilateral lesions of the vertical limb of the diagonal band of Broca and medial septum depleted ChAT from the hippocampus and posterior cortex but not the anterior cortex. Histological studies confirmed the accuracy of the lesion and showed a pronounced loss of acetylcholinesterase from the hippocampus. These rats were deficient in spatial learning and showed reduced spatial bias during transfer tests. The data are discussed in the light of the hypothesis that the cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation.     

Hallmarks of a common forebrain vertebrate plan: specialized pallial areas for spatial, temporal and emotional memory in actinopterygian fish

In mammals and birds different pallial forebrain areas participate in separate memory systems. In particular, the hippocampal pallium is implicated in spatial memory and temporal attribute processing, whereas the amygdalar pallium is involved in emotional memory. Here we analyze the involvement of teleost fish lateral and medial pallia, proposed as homologous to the hippocampus and amygdala, respectively, in a variety of learning and memory tasks, such as spatial memory; reversal learning; delay or trace motor classical conditioning; heart rate, emotional classical conditioning; and two way active avoidance conditioning. Results show that the damage to the lateral pallium produces a profound deficit in spatial learning and memory in teleost fish. In addition, lateral pallium lesions produce a significant deficit in trace classical conditioning, whereas they have no significant effects on delay conditioning, or in heart rate conditioning. In contrast, medial pallium lesions disrupt emotional, heart rate conditioning and avoidance conditioning, but spare spatial memory and temporal stimulus processing. These data demonstrate a striking functional similarity between the medial and lateral pallia of teleost fish and the pallial amygdala and hippocampal pallium of land vertebrates, respectively. The reviewed evidence suggest that these two separate memory systems, the hippocampus-dependent spatial, relational or temporal memory system, and the amygdala based emotional memory system, could have appeared early during evolution, having conserved their functional identity through vertebrate phylogenesis.     

Egocentric memory impaired and allocentric memory intact as assessed by virtual reality in subjects with unilateral parietal cortex lesions

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory mainly depends on inferior and superior parietal cortices. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. However, virtual reality studies on allocentric memory in subjects with cortical lesions are rare, and studies on egocentric memory are lacking. Twenty-four subjects with unilateral parietal cortex lesions due to infarction or intracerebral haemorrhage (14 left-sided, 10 right-sided) were compared with 36 healthy matched control subjects on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Subjects further received a comprehensive clinical and neuropsychological investigation, and MRI lesion assessment using T₁, T₂ and FLAIR sequences as well as 3D MRI volumetry at the time of the assessment. Results indicate that left- and right-sided lesioned subjects did not differ on task performance. Compared with control subjects, subjects with parietal cortex lesions were strongly impaired learning the virtual maze. On the other hand, performance of subjects with parietal cortex lesions on the virtual park was entirely normal. Volumes of the right-sided precuneus of lesioned subjects were significantly related to performance on the virtual maze, indicating better performance of subjects with larger volumes. It is concluded that parietal cortices support egocentric navigation and imagination during spatial learning in large-scale environments.     

Retrosplenial cortex lesions impair water maze strategies learning or spatial place learning depending on prior experience of the rat

There has been debate whether lesions strictly limited to retrosplenial (RS) cortex impair spatial navigation, and how robust and reliable any such impairment is. The present study used a detailed behavioral analysis with naive or strategies-pretrained rats given RS lesions and trained in a water maze (WM). Naive RS lesioned rats failed to acquire the required WM strategies throughout training. Strategies-pretrained RS lesioned rats were specifically impaired in spatial place memory without a WM strategies impairment. Additional training overcame the spatial memory impairment. Thus the behavioral consequences of the lesion depend on the specific previous experience of the animal. The use of appropriate training and testing techniques has revealed experience-dependant dissociable impairments in WM strategies learning and in spatial memory, indicating that RS cortex is involved in both forms of learning.     

Cooperation between the hippocampus and the entorhinal cortex in spatial memory: a disconnection study

It has been recently shown that lesions of parahippocampal areas including the entorhinal cortex do not disrupt place learning in the water maze, suggesting that the hippocampo-cortical circuitry is not important for spatial memory [Burwell RD, Saddoris MP, Bucci DJ, Wiig KA. Corticohippocampal contributions to spatial and contextual learning. J Neurosci 2004;24:3826-36]. The aim of the present study was to tax more directly the cooperation between the hippocampus and entorhinal cortex in two different spatial tasks, a place navigation task and a spontaneous object exploration task, using a disconnection procedure. Damaging the entorhinal-hippocampal system induced impairments in the two tasks but only in the spatial object exploration task rats with contralateral lesions displayed a greater deficit than rats with ipsilateral lesions. The results suggest that the cooperation between the hippocampus and the entorhinal cortex is modulated by the nature of the task and the cognitive processes involved in formation of spatial memory.     

Cholinergic modulation of spatial learning,memory and navigation

Spatial learning, including encoding and retrieval of spatial memories as well as holding spatial information in working memory generally serving navigation under a broad range of circumstances, relies on a network of structures. While central to this network are medial temporal lobe structures with a widely appreciated crucial function of the hippocampus, neocortical areas such as the posterior parietal cortex and the retrosplenial cortex also play essential roles. Since the hippocampus receives its main subcortical input from the medial septum of the basal forebrain (BF) cholinergic system, it is not surprising that the potential role of the septo‐hippocampal pathway in spatial navigation has been investigated in many studies. Much less is known of the involvement in spatial cognition of the parallel projection system linking the posterior BF with neocortical areas. Here we review the current state of the art of the division of labour within this complex ‘navigation system’, with special focus on how subcortical cholinergic inputs may regulate various aspects of spatial learning, memory and navigation.     

Hippocampal lesioned rats are able to learn a spatial position using non-spatial strategies

In the last two decades, many experiments have demonstrated that the hippocampus plays a role in the learning and processing of spatial and contextual information. Despite these demonstrations, some recent publications have indicated that the hippocampus is not the only structure involved in spatial learning and that even after hippocampal lesions, rats can perform spatial tasks. However, it is not well established whether animals with hippocampal dysfunction still have some spatial learning capacities or develop non-spatial solutions; these may require lengthier acquisition training. We now report the effects of conventional, dorsal hippocampal ablation on rats' performance on the water maze. We tested rats using a short (4 days) versus a long (16 days) acquisition period. We demonstrated that animals with dorsal hippocampal lesions have some residual capacity for learning the localization of a hidden escape platform in a pool during both a reference memory task and a working memory task. The animals with dorsal hippocampal lesions learned to escape at a fixed location, but only with extended training. It is suggested that these animals used non-spatial strategies to compensate for a spatial memory impairment. The results are discussed with respect to the experimental procedure and the strategy applied by the lesioned rats.     

Small lesions of the dorsal or ventral hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval,and combining them attenuates the acquisition rate of spatial reference memory

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over‐generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.     

Dissociation of item and order spatial memory in rats following medial prefrontal cortex lesions

In order to test whether there is a correspondence in function of prefrontal cortex in rats and humans, rats with medial prefrontal cortex lesions were tested for item and order memory for a list of items (spatial locations in a maze). Results indicate that for order memory rats with medial prefrontal cortex lesions cannot remember the order of presentation of four or eight specific spatial locations. This inability to remember order information can be seen even when animals with lesions have to remember only two spatial locations, can self-order the sequence of four or eight spatial locations, or have been presented with the same study phase on every trial. In contrast, for item memory animals with medial prefrontal cortex lesions retain the first item of the list in the variable study phase situation and remember all the items of the list in a constant study phase situation. However, there are also deficits for the last items within a list in the variable study phase situation for both win-stay and win-shift procedures. This deficit might be a function of an impairment in the utilization of appropriate temporal strategies, which normally would facilitate recognition memory in the win-stay and win-shift tasks. In general, the data suggest a partial, but not complete, dissociation of item-order memory. Furthermore, the data suggest that the medial prefrontal cortex is involved in temporal structuring of information.     

The effects of lesions to the caudolateral neostriatum on sun compass based spatial learning in homing pigeons

To better define the role of the avian caudolateral neostriatum (NCL) in spatial behavior, we used homing pigeons to explore the effects of NCL lesions on a sun compass based spatial learning task. Although NCL lesioned birds learned the task, they required more sessions to reach criterion than controls. NCL lesioned pigeons were also able to acquire a color discrimination task that was procedurally similar to the sun compass spatial learning task, but they made more errors than controls. Both the deficits observed in sun compass based spatial learning and color discrimination were correlated with the volume of lesion damage to dorsal rather than ventral portions of NCL. Overall, these findings suggest that the role of NCL in homing pigeon navigation from distant unfamiliar locations is not related to a bird's ability to learn stimulus-direction associations using a sun compass. However NCL does appear involved in a pigeon's ability to perform at least some behaviors common to both the color discrimination and the sun compass based spatial learning tasks.     

Deficits in allothetic and idiothetic spatial behavior in rats with posterior cingulate cortex lesions

The cingulate cortex plays a central role in bridging neocortical and limbic structures involved in allothetic navigation, a form of navigation requiring the use of external cues. Animals can also navigate using idiothetic cues, which are cues generated by self-movement, but there have been no definitive tests of whether cingulate cortex also plays a role in idiothetic navigation. Rats with anterior cingulate (medial frontal) and posterior cingulate cortex (retrosplenial) suction ablations were trained to search for large food pellets on an open table, and the accuracy with which they returned home with the food was measured. In the idiothetic task they searched for food from a novel starting location under infrared light, and with surface olfactory cues displaced. The rats also received two tests of allothetic navigation. They were tested on a matching-to-place task in which they foraged for food from a number of successively presented new locations under normal room light, and they were trained to locate a hidden platform in a swimming pool (Morris place task). The group with posterior cingulate cortex lesions was severely impaired on all of the navigation tasks whereas the group with anterior cingulate cortex lesions displayed no deficit on the idiothetic task and only moderate deficits on the other tasks. The results demonstrate a role for posterior cingulate region in idiothetic navigation.     

Experimentally altered navigational demands induce changes in the cortical forebrain of free-ranging northern pacific rattlesnakes (Crotalus o. oreganus)

The hippocampus of birds and mammals plays a crucial role in spatial memory and navigation. The hippocampus exhibits plasticity in adulthood in response to diverse environmental factors associated with spatial demands placed on an animal. The medial and dorsal cortices of the telencephalon of squamate reptiles have been implicated as functional homologues to the hippocampus. This study sought to experimentally manipulate the navigational demands placed on free-ranging northern Pacific rattlesnakes (Crotalus o. oreganus) to provide direct evidence of the relationship between spatial demands and neuroplasticity in the cortical telencephalon of the squamate brain. Adult male rattlesnakes were radio-tracked for 2 months, during which time 1 of 3 treatments was imposed weekly, namely 225-meter translocation in a random direction, 225-meter walk and release at that day's capture site (handling control) or undisturbed (control). Snakes were then sacrificed and the brains were removed and processed for histological analysis of cortical features. The activity range was larger in the translocated (Tr) group compared to the handled (Hd) and undisturbed control (Cn) groups when measured via 95% minimum convex polygon (MCP). At the 100% MCP level, Tr snakes had larger activity ranges than the Cn snakes only. The volume of the medial cortex (MC) was larger in the Tr group compared to the Cn group. The MC of Hd snakes was not significantly different from that of either of the other groups. No differences in dorsal cortex (DC) or lateral cortex volumes were detected among the groups. Numbers of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in the MC and DC 3 weeks after BrdU injection were not affected by treatment. This study establishes a causal relationship between navigational demands and greater MC volume in a free-ranging reptile.     

Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys

Visual recognition in monkeys appears to involve the participation of two limbothalamic pathways, one including the amygdala and the magnocellular portion of the medial dorsal nucleus (MDmc) and the other, the hippocampus and the anterior nuclei of the thalamus (Ant N). Both MDmc and Ant N project, in turn, to the prefrontal cortex, mainly to its ventral and medial portions. To test whether the prefrontal projection targets of the two limbothalamic pathways also participate in memory functions, performance on a variety of learning and memory tasks was assessed in monkeys with lesions of the ventromedial prefrontal cortex (Group VM). Normal monkeys and monkeys with lesions of dorsolateral prefrontal cortex (Group DL) served as controls. Group VM was severely impaired on a test of object recognition, whereas Group DL did not differ appreciably from normal animals. Conversely, the animals in Group VM were able to learn a spatial delayed response task, whereas 2 of the 3 animals in Group DL could not. Neither group was impaired in the acquisition of visual discrimination habits, even though the successive trials on a given discrimination were separated by 24-h intervals. The patterns of deficit suggest that ventromedial prefrontal cortex constitutes another station in the limbothalamic system underlying cognitive memory processes, whereas the dorsolateral prefrontal cortex lies outside this system. The results support the view that the classical delayed-response deficit observed after dorsolateral prefrontal lesions represents a perceptuo-mnemonic impairment in spatial functions selectively rather than a memory loss of a more general nature.     

Spatial learning in rats is impaired after degeneration of the nigrostriatal dopaminergic system.

We investigated spatial learning in rats with unilateral and bilateral lesions of the nigrostriatal dopaminergic system. We used the Morris water maze paradigm, which tests spatial forms of learning and memory and allows discrimination between sensory-motor and learning disabilities. Animals were trained preoperatively to learn the location of a spatially fixed hidden platform to escape from the swimming pool (acquisition training). A visual and a probe test were used before and after the acquisition training, respectively. Our results show that animals with unilateral lesions, although displaying longer escape latencies, have normal spatial memory abilities. Animals with bilateral lesions were able to swim as fast or even faster than animals with unilateral lesion. Despite the fact that these animals had learned the spatial navigation tasks preoperatively, bilateral dopaminergic lesions led to a profound deficit in ability to find a hidden platform during an acquisition task. In general, animals with bilateral lesions persisted in swimming along the pool walls and their spatial navigation performance during a probe test was very poor. These results suggest that deficit of the nigrostriatal dopaminergic system can affect the selection and maintenance of behavioral strategies in spatial navigation.