Beyond Spatial Memory: The Anterior Thalamus and Memory for the Temporal Order of a Sequence of Odor Cues

Influential recent proposals state that the anterior thalamic (AT) nuclei constitute key components of an “extended hippocampal system.” This idea is, however, based on lesion studies that used spatial memory tasks and there has been no evidence that AT lesions cause deficits in any hippocampal-dependent nonspatial tasks. The present study investigated the role of the AT nuclei in nonspatial memory for a sequence of events based on the temporal order of a list of odors, because this task has recently been shown to depend on the integrity of the hippocampal formation. After preoperative training, rats with excitotoxic lesions of the AT nuclei showed a severe and selective postoperative impairment when required to remember the order of pseudorandom sequences of six odors. The rats with AT lesions were able instead to learn two new tasks that required recognition memory and the identification of the prior occurrence of events independent of their order. These results strongly matched those described after hippocampal lesions and provide the first unequivocal evidence of a detrimental effect of an AT lesion on a nonspatial hippocampal-dependent memory task.

[1]  J. Aggleton,et al.  The effects of selective lesions within the anterior thalamic nuclei on spatial memory in the rat , 1996, Behavioural Brain Research.

[2]  R. C. Honey,et al.  Sensory preconditioning in rats with lesions of the anterior thalamic nuclei: evidence for intact nonspatial ‘relational’ processing , 2002, Behavioural Brain Research.

[3]  H. Shibata,et al.  Organization of projections of rat retrosplenial cortex to the anterior thalamic nuclei , 1998, The European journal of neuroscience.

[4]  John P. Aggleton,et al.  The Conjoint Importance of the Hippocampus and Anterior Thalamic Nuclei for Allocentric Spatial Learning: Evidence from a Disconnection Study in the Rat , 2001, The Journal of Neuroscience.

[5]  John B. Mitchell,et al.  The medial frontal cortex and temporal memory: tests using spontaneous exploratory behaviour in the rat , 1998, Behavioural Brain Research.

[6]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[7]  R. Passingham The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[8]  D. Béracochéa,et al.  Effects of anterior or dorsomedial thalamic ibotenic lesions on learning and memory in rats. , 1989, Behavioral and neural biology.

[9]  Paul E. Gilbert,et al.  The role of the hippocampus in memory for the temporal order of a sequence of odors. , 2002, Behavioral neuroscience.

[10]  J. Rawlins,et al.  Hippocampal aspiration lesions fail to impair performance of a delayed alternation GO/NO-GO task , 1992, Behavioural Brain Research.

[11]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[12]  H. Eichenbaum A cortical–hippocampal system for declarative memory , 2000, Nature Reviews Neuroscience.

[13]  J O'Keefe,et al.  An allocentric spatial model for the hippocampal cognitive map , 1991, Hippocampus.

[14]  Inga Kadish,et al.  Role of the anterodorsal and anteroventral nuclei of the thalamus in spatial memory in the rat , 2002, Behavioural Brain Research.

[15]  Amanda Parker,et al.  The effect of anterior thalamic and cingulate cortex lesions on object-in-place memory in monkeys , 1997, Neuropsychologia.

[16]  Hideshi Shibata,et al.  Organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei in the rat , 2005, Brain Research.

[17]  R. Mair,et al.  Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex. , 2003, Behavioral neuroscience.

[18]  M. Witter,et al.  Neuropsychology of infarctions in the thalamus: a review , 2000, Neuropsychologia.

[19]  J. Aggleton,et al.  Anterior thalamic lesions stop immediate early gene activation in selective laminae of the retrosplenial cortex: evidence of covert pathology in rats? , 2004, The European journal of neuroscience.

[20]  J. Pearce,et al.  Neural systems underlying episodic memory: insights from animal research. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[21]  G. Winocur The hippocampus and thalamus: Their roles in short- and long-term memory and the effects of interference , 1985, Behavioural Brain Research.

[22]  M. Petrides,et al.  The effects of lesions to the anterior thalamic nuclei on object–place associations in rats , 1999, The European journal of neuroscience.

[23]  H. Eichenbaum,et al.  Critical role of the hippocampus in memory for sequences of events , 2002, Nature Neuroscience.

[24]  M. W. Brown,et al.  Episodic memory, amnesia, and the hippocampal–anterior thalamic axis , 1999, Behavioral and Brain Sciences.

[25]  J. Muir,et al.  Does pretraining spare the spatial deficit associated with anterior thalamic damage in rats? , 1999, Behavioral neuroscience.

[26]  H. Shibata Direct projections from the anterior thalamic nuclei to the retrohippocampal region in the rat , 1993, The Journal of comparative neurology.

[27]  J. Kril,et al.  Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. , 2000, Brain : a journal of neurology.

[28]  H. Eichenbaum,et al.  The Hippocampus, Memory, and Place Cells Is It Spatial Memory or a Memory Space? , 1999, Neuron.

[29]  Raymond P. Kesner,et al.  An analysis of independence and interactions of brain substrates that subserve multiple attributes, memory systems, and underlying processes , 2004, Neurobiology of Learning and Memory.

[30]  L. Cooper,et al.  Memory for temporal order of new and familiar spatial location sequences: role of the medial prefrontal cortex. , 1997, Learning & memory.

[31]  M. A. Peinado-Manzano,et al.  The role of different nuclei of the thalamus in processing episodic information , 1991, Behavioural Brain Research.

[32]  John P Aggleton,et al.  Differential deficits in the Morris water maze following cytotoxic lesions of the anterior thalamus and fornix transection , 1998, Behavioural Brain Research.

[33]  J. Dalrymple-Alford,et al.  Perirhinal cortex and anterior thalamic lesions: comparative effects on learning and memory. , 2003, Behavioral neuroscience.

[34]  J. Michael Wyass,et al.  Connections between the retrosplenial cortex and the hippocampal formation in the rat: A review , 1992, Hippocampus.

[35]  R P Kesner,et al.  Memory for frequency in rats: role of the hippocampus and medial prefrontal cortex. , 1990, Behavioral and neural biology.

[36]  R. O. Hopkins,et al.  Item and Order Recognition Memory in Subjects with Hypoxic Brain Injury , 1995, Brain and Cognition.

[37]  R. Kesner Neural mediation of memory for time: Role of the hippocampus and medial prefrontal cortex , 1998 .

[38]  John P Aggleton,et al.  Fos Imaging Reveals that Lesions of the Anterior Thalamic Nuclei Produce Widespread Limbic Hypoactivity in Rats , 2002, The Journal of Neuroscience.

[39]  R P Kesner,et al.  Memory for spatial location as a function of temporal lag in rats: role of hippocampus and medial prefrontal cortex. , 1994, Behavioral and neural biology.

[40]  J. Michael Wyss,et al.  Efferent connections of the anteromedial nucleus of the thalamus of the rat , 1999, Brain Research Reviews.

[41]  T. van Groen,et al.  Projections from the anterodorsal and anteroveniral nucleus of the thalamus to the limbic cortex in the rat , 1995, The Journal of comparative neurology.

[42]  J. Aggleton,et al.  The mammillary bodies: two memory systems in one? , 2004, Nature Reviews Neuroscience.

[43]  Anna S. Mitchell,et al.  Dissociable memory effects after medial thalamus lesions in the rat , 2005, The European journal of neuroscience.

[44]  M Petrides,et al.  Effects of lesions to the hippocampus or the fornix on allocentric conditional associative learning in rats , 2002, Hippocampus.

[45]  A. Phillips,et al.  Medial prefrontal cortex is involved in spatial temporal order memory but not spatial recognition memory in tests relying on spontaneous exploration in rats , 2004, Behavioural Brain Research.

[46]  A. Célérier,et al.  Deficits of spatial and non‐spatial memory and of auditory fear conditioning following anterior thalamic lesions in mice: comparison with chronic alcohol consumption , 2000, The European journal of neuroscience.

[47]  G. Byatt,et al.  Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats. , 1996, Behavioral neuroscience.

[48]  Raymond P. Kesner,et al.  Memory for Duration: Role of Hippocampus and Medial Prefrontal Cortex , 1998, Neurobiology of Learning and Memory.

[49]  H. Eichenbaum,et al.  Neurotoxic Hippocampal Lesions Have No Effect on Odor Span and Little Effect on Odor Recognition Memory But Produce Significant Impairments on Spatial Span, Recognition, and Alternation , 2000, The Journal of Neuroscience.