A Disconnection Analysis of the Hippocampal Formation’s Role in Working Memory

Although the hippocampal formation has been established as an essential structure for learning and memory, its contribution to working memory remains controversial. Here, we aimed to elucidate the role of the hippocampal formation, fimbria-fornix, and entorhinal cortex in working memory using a disconnection model in rats. After reaching criterion on a Delayed-Non- Matching-to-Position (DNMTP) task in an operant chamber, rats were randomly assigned to one of five surgical groups: (1) bilateral fimbria-fornix transection (BFFx); (2) bilateral entorhinal cortex lesion (BECx); (3) unilateral entorhinal cortex + contralateral fimbria-fornix transection lesion (ECxFFx); (4) unilateral entorhinal cortex lesion + contralateral dorsal psalterium and fimbria-fornix transection (ECxDPx); (5) sham craniotomy (SC). Post-operative behavioral testing began after a 6-12 day recovery period and continued until 64 daily sessions were completed. DNMTP performance was observed to be delay-dependent, confirming its ability to measure mnemonic function. All four lesion groups demonstrated working memory impairment in early post-operative testing. The BECx, ECxFFx, and ECxDPx groups showed recovery to levels of sham animals within three weeks of testing. The BFFx group resulted in a permanent working memory deficit that was significant across the twelve weeks of testing. A right side bias, a type of perseverative behavior, was present during periods of otherwise impaired performance in all three groups that were subjected to fimbria-fornix transection. Histological analysis confirmed lesion placement, and histochemical staining indicated lesion-induced acetylcholinesterase-containing sprouting, a measure of cholinergic septodentate sprouting, in hemispheres with an ablated entorhinal cortex. The pattern of behavioral recovery suggested the septohippocampal pathway might be essential for normal working memory function and the recovery of function following injury.
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Abstract/Description: Although the hippocampal formation has been established as an essential structure for learning and memory, its contribution to working memory remains controversial. Here, we aimed to elucidate the role of the hippocampal formation, fimbria-fornix, and entorhinal cortex in working memory using a disconnection model in rats. After reaching criterion on a Delayed-Non- Matching-to-Position (DNMTP) task in an operant chamber, rats were randomly assigned to one of five surgical groups: (1) bilateral fimbria-fornix transection (BFFx); (2) bilateral entorhinal cortex lesion (BECx); (3) unilateral entorhinal cortex + contralateral fimbria-fornix transection lesion (ECxFFx); (4) unilateral entorhinal cortex lesion + contralateral dorsal psalterium and fimbria-fornix transection (ECxDPx); (5) sham craniotomy (SC). Post-operative behavioral testing began after a 6-12 day recovery period and continued until 64 daily sessions were completed. DNMTP performance was observed to be delay-dependent, confirming its ability to measure mnemonic function. All four lesion groups demonstrated working memory impairment in early post-operative testing. The BECx, ECxFFx, and ECxDPx groups showed recovery to levels of sham animals within three weeks of testing. The BFFx group resulted in a permanent working memory deficit that was significant across the twelve weeks of testing. A right side bias, a type of perseverative behavior, was present during periods of otherwise impaired performance in all three groups that were subjected to fimbria-fornix transection. Histological analysis confirmed lesion placement, and histochemical staining indicated lesion-induced acetylcholinesterase-containing sprouting, a measure of cholinergic septodentate sprouting, in hemispheres with an ablated entorhinal cortex. The pattern of behavioral recovery suggested the septohippocampal pathway might be essential for normal working memory function and the recovery of function following injury.
Subject(s): Neuroscience
Date Issued: May 2014