Anterior thalamic lesions reduce spine density in both hippocampal CA1 and retrosplenial cortex, but enrichment rescues CA1 spines only

Abstract

Injury to the anterior thalamic nuclei (ATN) may affect both hippocampus and retrosplenial cortex thus explaining some parallels between diencephalic and medial temporal lobe amnesias. We found that standard-housed rats with ATN lesions, compared with standard-housed controls, showed reduced spine density in hippocampal CA1 neurons (basal dendrites, -11.2%; apical dendrites, -9.6%) and in retrospenial granular b cortex (Rgb) neurons (apical dendrites, -20.1%) together with spatial memory deficits on cross maze and radial-arm maze tasks. Additional rats with ATN lesions were also shown to display a severe deficit on spatial working memory in the cross-maze, but subsequent enriched housing ameliorated their performance on both this task and the radial-arm maze. These enriched rats with ATN lesions also showed recovery of both basal and apical CA1 spine density to levels comparable to that of the standard-housed controls, but no recovery of Rgb spine density. Inspection of spine types in the CA1 neurons showed that ATN lesions reduced the density of thin spines and mushroom spines, but not stubby spines; while enrichment promoted recovery of thin spines. Comparison with enriched rats that received pseudo-training, which provided comparable task-related experience, but no explicit spatial memory training, suggested that basal CA1 spine density in particular was associated with spatial learning and memory performance. Distal pathology in terms of reduced integrity of hippocampal and retrosplenial microstructure provides clear support for the influence of the ATN lesions on the extended hippocampal system. The reversal by postoperative enrichment of this deficit in the hippocampus but not the retrosplenial cortex may indicate region-specific mechanisms of recovery after ATN injury.

Anterior thalamic nuclei lesions have a greater impact than mammillothalamic tract lesions on the extended hippocampal system

“…Previously, only separate studies have been available to estimate the comparative effects of MTT and ATN lesions on memory tasks. The similar effects of both lesion types have been emphasized, in that neither lesion impairs novel object discrimination (Moran & Dalrymple‐Alford, ; Nelson & Vann, ; Warburton & Aggleton, ), but both lesions impair temporal memory for a sequence of items (Dumont & Aggleton, ; Nelson & Vann, ; Wolff et al, ,b) and both lesions impair spatial working memory in radial‐arm maze tasks (Aggleton, Hunt, Nagle, & Neave, ; Harland, Collings, McNaughton, Abraham, & Dalrymple‐Alford, ; Mitchell & Dalrymple‐Alford, ; Nelson & Vann, ; Sziklas & Petrides, ; Vann, ; Vann & Aggleton, ). The greater severity of spatial working memory deficits after ATN lesions reported here is reminiscent of the T‐maze alternation deficits found previously across separate ATN or MTT lesion studies.…”

Environmental enrichment increases prefrontal EEG power and synchrony with the hippocampus in rats with anterior thalamus lesions

“…However, in the hippocampus at least, we can be sure that rhythmicity, in and of itself, is important for behavioral plasticity (McNaughton et al, ). How far dmPFC or hippocampal changes in rhythmicity relate to the morphological changes that occur with ATN lesions and EE (Harland et al, ) remains to be determined.…”

“…Importantly, environmental enrichment (EE) ameliorates the amnestic effects of ATN lesions (Dalrymple‐Alford et al, ; Harland, Collings, McNaughton, Abraham, & Dalrymple‐Alford, ; Loukavenko, Ottley, Moran, Wolff, & Dalrymple‐Alford, ; Loukavenko, Wolff, Poirier, & Dalrymple‐Alford, ; Wolff, Loukavenko, Will, & Dalrymple‐Alford, ). Recent studies also suggest that EE influences network activity within the hippocampus (Shinohara, Hosoya, & Hirase, ) and can enhance gamma oscillations in mice and rats (Tanaka, Wang, Mikoshiba, Hirase, & Shinohara, ).…”

“…Recent studies also suggest that EE influences network activity within the hippocampus (Shinohara, Hosoya, & Hirase, ) and can enhance gamma oscillations in mice and rats (Tanaka, Wang, Mikoshiba, Hirase, & Shinohara, ). While ATN lesions reduce immediate early gene expression and spine counts in the retrosplenial cortex, only the reduction in spine number on CA1 neurones is (partially) reversed by EE (Aggleton, ; Dumont & Aggleton, ; Dupire et al, ; Harland et al, ; Jenkins, Dias, Amin, Brown, & Aggleton, ; Jenkins, Vann, Amin, & Aggletion, ; Loukavenko et al, ). This suggests that the hippocampus may be important for the capacity of EE to reduce diencephalic amnesia; but the mechanisms of this effect remain to be explored.…”

The retrosplenial cortex and object recency memory in the rat

“…The same dissociation is also often seen after hippocampal lesions, i.e. impaired recency but spared recognition memory (Cho & Sharp, ; Vann & Aggleton, ; Pothuizen et al ., ; Harland et al ., ; Nelson et al ., ; Albasser et al ., ). This shared pattern of deficits is striking given the many interconnections between these same sites.…”