Anterior but not intralaminar thalamic nuclei support allocentric spatial memory
Introduction
Medial thalamic injury is a common cause of severe memory disruption in humans (Kopelman, 2002, Van der Werf et al., 2000, Van der Werf et al., 2003). The critical thalamic regions that contribute to diencephalic amnesia are, however, unclear as non-specific brain damage often occurs in clinical cases. Separate lines of evidence in rat lesion models have focussed on the anterior thalamic nuclei (ATN) or the adjacent intralaminar thalamic nuclei (ILN) as two key regions that are likely to cause memory impairment after injury (Aggleton and Brown, 1999, Aggleton and Brown, 2006, Aggleton and Pearce, 2001, Mair, 1994, Mair et al., 2003). Unfortunately, the interpretation of many of these experimental studies is confounded by the potential influence of overlap in lesion extent or the use of conventional lesions that disrupt the complex fiber pathways that traverse this region. The present study explicitly addressed this problem by providing a direct comparison between the effects of highly selective neurotoxic lesions to the ATN and the ILN in rats using behavioral tasks that compared different spatial abilities.
Previous studies that examined lesions targeted at either the ATN or ILN provide some indications as to the comparative learning and memory processes that are disrupted by injury to these regions. The view that the ILN play a significant role in learning and memory is supported by delay-independent memory deficits in rats with ILN lesions when tested in a variety of matching and non-matching to sample tasks, including object, auditory, olfactory, retractable-lever and maze-arm stimuli (Bailey and Mair, 2005, Burk and Mair, 1998, Harrison and Mair, 1996, Young et al., 1996, Zhang et al., 1998). Damage to the ATN is most commonly associated with allocentric spatial memory impairment (Byatt and Dalrymple-Alford, 1996, Celerier et al., 2000, Mitchell and Dalrymple-Alford, 2005, Moran and Dalrymple-Alford, 2003, van Groen et al., 2002, Warburton and Aggleton, 1999, Warburton et al., 1997), which may reflect an interdependency between the ATN and the hippocampal system (Warburton et al., 2000, Warburton et al., 2001). Such findings support the hypothesis that the ATN and the hippocampus constitute essential components of an extended system underlying episodic memory (Aggleton and Brown, 1999, Aggleton and Pearce, 2001), which is consistent with recent studies on clinical cases that emphasize the deleterious effect of ATN damage in diencephalic amnesia (Caulo et al., 2005, Gold and Squire, 2006, Harding et al., 2000). A severe impairment in allocentric spatial memory in the Morris water maze has also been reported in rats with ILN lesions (Mair et al., 1998, Savage et al., 1998), but it is unclear whether encroachment of these ILN lesions to the adjacent ATN can account for these results (Mair et al., 2003). In a similar vein, there is mixed evidence whether the extension to adjacent thalamic structures also contributes to spatial memory impairments found after large ATN lesions (Warburton and Aggleton, 1999, Warburton et al., 1999, Warburton et al., 1997).
Recent studies have begun to focus on more selective, subtotal lesions to the ATN and the ILN. For example, Mair and his colleagues have shown that ATN lesions induce a delay-dependent impairment when varying arms in a radial maze are used for a non-matching to sample task (Mair et al., 2003), whereas restricted ILN lesions have no effect (Bailey & Mair, 2005). Our laboratory has explicitly contrasted rats with selective ATN and ILN lesions that have as minimal overlap as possible from one region to the next. As these ILN lesions included the adjacent lateral region of the mediodorsal (MD) thalamic nucleus, we have previously labeled these “lateral thalamic” (LT) lesions. This lateral MD region is impossible to avoid when making neurotoxic ILN lesions, but all the nuclei in this ILN/LT region have overlapping prefrontal and striatal connections (Berendse and Groenewegen, 1991, Mitchell and Dalrymple-Alford, 2005, Van der Werf et al., 2002). We found that ATN lesions severely impaired preoperatively-trained working and reference memory in a radial-arm maze, whereas rats with ILN rats exhibited only a very mild and transient working memory deficit (Mitchell & Dalrymple-Alford, 2005). A second study revealed a double dissociation in which only ATN lesions impaired the post-operative acquisition of spatial working memory in a radial-arm maze, whereas only ILN lesions produced a deficit on a preoperatively acquired response-related (egocentric) working memory task in a cross maze (Mitchell & Dalrymple-Alford, 2006). However, both ATN and ILN lesions produced severe impairments when the rats were required to learn arbitrary associations between an odor and a place (Gibb, Wolff, & Dalrymple-Alford, 2006), an ability that also requires the functional integrity of the hippocampus (Gilbert & Kesner, 2002). Together with uncertainty in terms of their effects on acquisition of spatial memory in the water maze, the latter finding suggests that the ATN and the ILN may sometimes produce similar impairments on learning and memory tasks and that both perhaps mediate some aspects of hippocampal-dependent learning.
A direct examination of the involvement of these two thalamic regions on spatial memory that does or does not require the hippocampus is therefore warranted. Hippocampal system functions are believed to support allocentric spatial memory but not egocentric spatial processing, whereas the reverse is generally true of the dorsal striatum (Cook and Kesner, 1988, DeCoteau and Kesner, 2000, Kesner et al., 1993, McDonald and White, 1993, McDonald and White, 1994, Morris et al., 1990, Packard and Teather, 1998). It is particularly interesting that one perspective that has emerged from the recent thalamic lesion literature is that ILN lesions, but not ATN lesions, impair egocentric spatial working memory tasks (Bailey and Mair, 2005, Mair et al., 1998, Mair et al., 2003, Mitchell and Dalrymple-Alford, 2006), which is consistent with the above-mentioned fact that some of the prominent connections of the ILN/LT region are with the dorsal striatum and dorsal prefrontal cortex (Van der Werf et al., 2002). If ILN/LT lesions impair functions associated with the dorsal striatum, then these thalamic lesions should also disrupt other egocentric spatial memory and response-related learning tasks that have been shown to be sensitive to caudate lesions. A severe impairment with dorsal caudate lesions has been reported when rats were trained on a left/right discrimination task in a Y-maze, especially when distal spatial cues are minimized (Mitchell and Hall, 1987, Mitchell and Hall, 1988). As ATN damage appears to influence hippocampal-dependent, allocentric spatial memory, but does not appear to disrupt egocentric (response-related) spatial reference memory (Aggleton et al., 1996, Warburton et al., 1997), we tested the prediction that selective ATN and ILN lesions would produce a double dissociation across spatial memory in the Morris water maze and a water adaptation of left/right discrimination in a Y-maze. The use of two swimming tasks ensured that the basic motivational and motor requirements remained the same while the spatial memory demands differed across the two tasks.
Section snippets
Subjects and housing conditions
Male PVGc hooded rats, bred in-house, were maintained in groups of three or four in standard opaque plastic cages (27 cm × 45 cm wide × 22 cm high). All rats were housed under a reversed light schedule (off 8am to 8pm) and testing occurred during the dark phase of the cycle. Food and water was available ad libitum. They were 7–8 months old with a mean body weight of 355 g at surgery and were 8–9 months old at the start of testing. All protocols conformed to the NIH Guide for the Care and Use of
Histology
As in previous work (e.g., Gibb et al., 2006), acceptable lesions were defined as having significant (50%) bilateral damage to the intended target as long as there was little damage to the comparison region (i.e. ATN or ILN/LT). Fig. 1 shows the largest and smallest acceptable ATN (Fig. 1A) and ILN/LT (Fig. 1B) lesions as well as typical ATN (Fig. 1C) and ILN/LT (Fig. 1D) lesion visualized with NeuN staining. Four ATN rats and three ILN/LT rats experienced either a failed or small lesion and
Discussion
The current study contrasted the effects of neurotoxic thalamic lesions to the ATN and the ILN/LT region in rats on two different spatial memory tasks taxing either allocentric or egocentric spatial reference memory that required the same general motivational and sensori-motor demands. The prediction that selective ATN lesions, but not ILN/LT lesions, would impair allocentric spatial memory in the Morris maze was confirmed and this direct comparison helps clarify some conflicting previous
Acknowledgments
The authors gratefully acknowledge the support of the Neurological Foundation of New Zealand and the Department of Psychology of the University of Canterbury. Mathieu Wolff was supported by a Lavoisier post-doctoral fellowship from the French government and Sheree Gibb was supported by a NZ Tertiary Education Commission Top Achiever Doctoral Scholarship.
References (56)
- et al.
Interleaving brain systems for episodic and recognition memory
Trends in Cognitive Science
(2006) - et al.
The effects of selective lesions within the anterior thalamic nuclei on spatial memory in the rat
Behavioural Brain Research
(1996) - et al.
Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat
Neuroscience
(1991) - et al.
Fimbria-fornix vs selective hippocampal lesions in rats: Effects on locomotor activity and spatial learning and memory
Neurobiology of Learning and Memory
(1998) - et al.
Caudate nucleus and memory for egocentric localization
Behavioral and Neural Biology
(1988) - et al.
Odour-place paired-associate learning and limbic thalamus: Comparison of anterior, lateral and medial thalamic lesions
Behavioural Brain Research
(2006) - et al.
A comparison of the effects of frontal cortical and thalamic lesions on measures of spatial learning and memory in the rat
Behavioural Brain Research
(1996) - et al.
An examination of the spatial working memory deficit following neurotoxic medial dorsal thalamic lesions in rats
Behavioural Brain Research
(1998) - et al.
Specific neuronal protein: A new tool for histological evaluation of excitotoxic lesions
Physiology and Behavior
(2002) - et al.
An analysis of independence and interactions of brain substrates that subserve multiple attributes, memory systems, and underlying processes
Neurobiology of Learning and Memory
(2004)
Parallel information processing in the water maze: Evidence for independent memory systems involving dorsal striatum and hippocampus
Behavioral and Neural Biology
Amygdala modulation of multiple memory systems: Hippocampus and caudate-putamen
Neurobiology of Learning and Memory
Hippocampal lesioned rats are able to learn a spatial position using non-spatial strategies
Behavioural Brain Research
Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions
Neuropsychologia
The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness
Brain Research Brain Research Reviews
Neuropsychology of infarctions in the thalamus: A review
Neuropsychologia
Role of the anterodorsal and anteroventral nuclei of the thalamus in spatial memory in the rat
Behavioural Brain Research
Assessing the magnitude of the allocentric spatial deficit associated with complete loss of the anterior thalamic nuclei in rats
Behavioural Brain Research
Dissociation of function within the hippocampus: Effects of dorsal, ventral and complete excitotoxic hippocampal lesions on spatial navigation
Neuroscience
Episodic memory, amnesia, and the hippocampal-anterior thalamic axis
Behavioral and Brain Sciences
Neural systems underlying episodic memory: Insights from animal research
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Lesions of specific and nonspecific thalamic nuclei affect prefrontal cortex-dependent aspects of spatial working memory
Behavioral Neuroscience
Double dissociation of function within the hippocampus: A comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions
Behavioral Neuroscience
Spatial learning in the 5-HT1B receptor knockout mouse: Selective facilitation/impairment depending on the cognitive demand
Learning and Memory
Thalamic amnesia reconsidered: Excitotoxic lesions of the intralaminar nuclei, but not the mediodorsal nucleus, disrupt place delayed matching-to-sample performance in rats (Rattus norvegicus)
Behavioral Neuroscience
Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats
Behavioral Neuroscience
Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome
Brain
Deficits of spatial and non-spatial memory and of auditory fear conditioning following anterior thalamic lesions in mice: Comparison with chronic alcohol consumption
European Journal of Neuroscience
Cited by (54)
Time to retire the serial Papez circuit: Implications for space, memory, and attention
2022, Neuroscience and Biobehavioral ReviewsThe role of the anterior nuclei of the thalamus in human memory processing
2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :These findings point to a dependency on the ATN for the acquisition of new information, that is, memory encoding. These lesion studies provide support in humans for conclusions drawn in lesion-based animal studies indicating a potentially causal role for the ATN in memory processing (Dalrymple-Alford et al., 2015; Mitchell and Dalrymple-Alford, 2006; Warburton et al., 2000; Wolff et al., 2008). Seizures are not adequately controlled using medication in approximately fifteen percent of patients with epilepsy (Kalilani et al., 2018).
The anterior thalamic nuclei and nucleus reuniens: So similar but so different
2020, Neuroscience and Biobehavioral ReviewsCerebral perfusion mapping during retrieval of spatial memory in rats
2019, Behavioural Brain ResearchEn route to delineating hippocampal roles in spatial learning
2019, Behavioural Brain Research