Anterior thalamic nuclei: A critical substrate for non‐spatial paired‐associate memory in rats

• Published in: The European journal of neuroscience 2022-10, Vol.56 (7), p.5014-5032
• Main Authors: Hamilton, Jennifer J., Dalrymple‐Alford, John C.
• Format: Article
• Language: English
• Subjects: Amnesia; Animals; Anterior Thalamic Nuclei - pathology; Anterior Thalamic Nuclei - physiology; Associative learning; Behavioral Neuroscience; biconditional discrimination; Cues; EGR-1 protein; extended memory system; Hippocampus - physiology; immediate early genes; Information processing; Lesions; Male; Maze Learning - physiology; Mental task performance; Odor; rat; Rats; Research Report; Rodents; Sensory integration; Spatial memory; Spatial Memory - physiology; thalamic amnesia; Thalamic Nuclei; Thalamus
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15802

Injury or dysfunction in the anterior thalamic nuclei (ATN) may be the key contributory factor in many instances of diencephalic amnesia. Experimental ATN lesions impair spatial memory and temporal discriminations, but there is only limited support for a more general role in non‐spatial memory. To extend evidence on the effects of ATN lesions, we examined the acquisition of biconditional associations between odour and object pairings presented in a runway, either with or without a temporal gap between these items. Intact adult male rats acquired both the no‐trace and 10‐s trace versions of this non‐spatial task. Intact rats trained in the trace version showed elevated Zif268 activation in the dorsal CA1 of the hippocampus, suggesting that the temporal component recruited additional neural processing. ATN lesions completely blocked acquisition on both versions of this association‐memory task. This deficit was not due to poor inhibition to non‐rewarded cues or impaired sensory processing, because rats with ATN lesions were unimpaired in the acquisition of simple odour discriminations and simple object discriminations using similar task demands in the same apparatus. This evidence challenges the view that impairments in arbitrary paired‐associate learning after ATN lesions require the use of multimodal spatial stimuli. It suggests that diencephalic amnesia associated with the ATN stems from degraded attention to stimulus–stimulus associations and their representation across a distributed memory system. The anterior thalamic nuclei (ATN) form a strategic node in a distributed memory system by virtue of connections with frontal cortex, hippocampal formation and retrosplenial cortex. Evidence on memory deficits after ATN lesions has overwhelmingly come from spatial or temporal tasks. Here, ATN lesions completely blocked the ability to learn a non‐spatial odour–object association memory. This new deficit reinforces the link between ATN dysfunction and diencephalic amnesia.