Abstract
In two related experiments, neurotoxic lesions were placed in the anterior thalamic nuclei of adult rats. The rats were then trained on behavioral tasks, immediately followed by the immunohistochemical measurement of molecules linked to neural plasticity. These measurements were made in limbic sites including the retrosplenial cortex, the hippocampal formation, and parahippocampal areas. In Experiment 1, rats with unilateral anterior thalamic lesions explored either novel or familiar objects prior to analysis of the immediate-early gene zif268. The lesions reduced zif268 activity in the granular retrosplenial cortex and postsubiculum. Exploring novel objects resulted in local changes of hippocampal zif268, but this change was not moderated by anterior thalamic lesions. In Experiment 2, rats that had received either bilateral anterior thalamic lesions or control surgeries were exposed to novel room cues while running in the arms of a radial maze. In addition to zif268, measurements of c-AMP response element binding protein (CREB), phosphorylated CREB (pCREB), and growth associated protein43 (GAP-43) were made. As before, anterior thalamic lesions reduced zif268 in retrosplenial cortex and postsubiculum, but there were also reductions of pCREB in granular retrosplenial cortex. Again, the hippocampus did not show lesion-induced changes in zif268, but there were differential effects on CREB and pCREB consistent with reduced levels of hippocampal CREB phosphorylation following anterior thalamic damage. No changes in GAP-43 were detected. The results not only point to changes in several limbic sites (retrosplenial cortex and hippocampus) following anterior thalamic damage, but also indicate that these changes include decreased levels of pCREB. As pCREB is required for neuronal plasticity, partly because of its regulation of immediate early-gene expression, the present findings reinforce the concept of an ‘extended hippocampal system’ in which hippocampal function is dependent on distal sites such as the anterior thalamic nuclei.
Highlights
Behavioral experiments have shown that anterior thalamic–hippocampal interactions are critical for spatial and contextual memory (Parker and Gaffan, 1997a,b; Aggleton and Brown, 1999; Warburton et al, 2000, 2001; Henry et al, 2004)
Two related experiments examined the impact of anterior thalamic lesions on the activity of the hippocampus and related limbic regions by assaying levels of various molecules linked to neuronal plasticity
Measurements were made of several molecules linked to neuronal plasticity in a set of limbic sites related to anterior thalamic function
Summary
Behavioral experiments have shown that anterior thalamic–hippocampal interactions are critical for spatial and contextual memory (Parker and Gaffan, 1997a,b; Aggleton and Brown, 1999; Warburton et al, 2000, 2001; Henry et al, 2004). The present study sought to understand why the anterior thalamic nuclei and hippocampus are often interdependent. For this reason, two related experiments examined the impact of anterior thalamic lesions on the activity of the hippocampus and related limbic regions by assaying levels of various molecules linked to neuronal plasticity. Previous studies have shown how anterior thalamic lesions can reduce activity of the immediate early gene (IEG) c-fos within the hippocampus (Jenkins et al, 2002a,b; see Vann and Albasser, 2009), potentially helping to explain why such lesions disrupt spatial memory tasks (see Liu et al, 2012). The present study pursued this inter-relationship by comparing the consequences of lesions in the anterior thalamic nuclei on activity levels of another IEG, zif268 ( known as egr-1 or krox). The IEG zif268 was studied as its expression is often closely associated with hippocampal plasticity and so it appears to be involved in spatial learning and memory
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