Chitoku Miwa

Impairment in the acquisition of passive and active avoidance learning tasks due to bilateral entorhinal cortex lesions

The relationship between the entorhinal cortex and learning behavior was examined. The initial stage of Alzheimers disease has been shown to be characterized by neuropathological alteration in the entorhinal cortex, with the appearance of the greatest number of neuronal tangles and severe neuronal loss in comparison with other brain regions involved. This entorhinal cortex, because of its anatomical relationship to the hippocampus, may play a crucial role in memory formation. In this study, rats with bilateral ibotenic acid-induced lesions of the entorhinal cortices were tested for acquisition of passive and active avoidance learning tasks. These animals displayed no sensorimotor disturbances as shown by evaluation of locomotor activity and shock sensitivity. However, they did show impair acquisition of passive and active avoidance responses. On the other hand, when the lesions were induced after training, there was no extinction of the acquired passive and active avoidance responses. The results demonstrate the importance of the entorhinal cortex in learning acquisition and indicate that rats with partial neuronal loss in the entorhinal cortex may be a useful model for studying the memory disturbance of Alzheimers disease.

Synapse alteration in hippocampal CA3 field following entorhinal cortex lesion

To model one aspect of the neurodegeneration observed in Alzheimers disease and to investigate the synaptic alteration of the hippocampus associated with entorhinal cortex lesion, ibotenic acid was used to produce selective unilateral neuronal loss in rat entorhinal cortex. Immunohistological and microdensitometrical analyses confirmed ibotenic acid lesion of the entorhinal cortex after 3 months and showed a decrease of synaptophysin-immunoreactive substances in the stratum lucidum of the CA3 field. This study demonstrates that entorhinal cortex lesion can lead to synaptic alterations and cause damage to presynaptic terminals with projecting area in the disruption of the entorhinal cortex hippocampus relay passage.

Depression in multiple system atrophy: A case report

Abstract A 53‐year‐old woman who developed depression as the first symptom of multiple system atrophy was treated. Depression was followed successively by autonomic failure, parkinsonism and cerebellar ataxia. Treatment with L‐DOPA, L‐threo‐DOPS, and thyroid releasing hormone was associated with improvement of autonomic failure and parkinsonism. As for depression, scores on the Zung scale and the Hamilton scale improved from 58 to 49 and from 30 to 22, respectively. This case is remarkable in that depression preceded neurologic dysfunction and was managed successfully by antiparkinsonian medication. A common underlying disturbance may be responsible for the depression and neurologic dysfunction in multiple system atrophy.

Effects of entorhinal cortex lesion on learning behavior and on hippocampus in the rat

The initial stage of Alzheimers disease is characterized by a neuropathological change in the entorhinal cortex. In a previous study it was shown that rats with excitotoxic lesion of entorhinal cortex showed an impaired acquisition of passive and active avoidance responses. In this study a rat with excitotoxic lesion of the entorhinal cortex was tested for ‘more operant’ behavioral learning (i.e., positive reinforcement operant learning). The hippocampus was also examined histologically as acetylcholinesterase‐stained sections, and as synaptophysin immunostained sections and examined biochemically by liquid chromatography. Eight weeks after operation, the bilateral entorhinal cortex lesioned rats showed an impaired acquisition of positive reinforcement operant learning. The lesioned side of unilateral entorhinal cortex lesioned rats showed a decrease of acecylcholinesterase‐positive fibers in the CA3, the dentate gyrus, and of synaptophysin‐positive substances in the CA3. Biochemical study showed a decreased level of acetylcholine in the CA3, and in the dentate gyrus. The histological and biochemical findings are interpreted as indicating that the entorhinal cortex of the rat provides the major extrinsic synaptic input to the hippocampal formation via the circuit which serves as a relay passage through the dentate gyrus and via direct projections into the hippocampus. Behavioral findings confirmed the importance of the entorhinal cortex in memory acquisition and indicated that rats with a partial neuronal loss in the entorhinal cortex may be a useful model for the memory disturbance of Alzheimers disease.

Histological evidence for cholinergic alteration in the hippocampus following entorhinal cortex lesion

The initial stage of Alzheimers disease is characterized by neuropathological alteration in the entorhinal cortex. To model one aspect of the neurodegeneration observed and to investigate anatomical changes of the hippocampus associated with unilateral entorhinal cortex lesion, excitotoxin ibotenic acid was used to produce selective unilateral neuronal loss in rat entorhinal cortex. Histological and morphometrical analyses confirmed excitotoxic lesion of the entorhinal cortex after 3 months and showed a decrease of acetylcholineste-rase-stained fibers in the stratum moleculare of the dentate gyrus and the stratum radiatum of the CA3 field. This study demonstrates the importance of the entorhinal cortex in the hippocampal cholinergic function which appears to be important to memory and learning, and raises the possibility that memory deficit in Alzheimers disease may be associated with partial neuronal loss in the entorhinal cortex.

Effect of entorhinal cortex lesion on hippocampal cholinergic system in rat in operant learning task as studied by in vivo brain microdialysis

An in vivo microdialysis method was used to study the cholinergic alteration of the hippocampus in entorhinal cortex-lesioned rats performing a positive reinforcement operant learning task. Rats with bilateral entorhinal cortex lesions were implanted with a dialysis probe into the hippocampal CA3 after ten learning sessions. After 7 days, the bilateral entorhinal cortex-lesioned rats showed impaired acquisition of positive reinforcement operant learning. The basal level of the acetylcholine efflux decreased within 30 min before the beginning of a learning session. The hippocampal acetylcholine efflux showed a significantly diminished increase and rapidly returned to the basal level during the 60 min after the beginning of a learning session. These results suggested that enorhinal cortex lesion may cause damage to the hippocampal cholinergic system with disruption of the entorhinal cortex-hippocampus relay passage.

Long-term synaptic alteration in the rat hippocampal CA3 field following an entorhinal cortex lesion

Abstract The entorhinal cortex is a key initial relay for cortical input to the hippocampus. To better understand hippocampal dysfunction resulting from early entorhinal cortex involvement in Alzheimer’s disease, we stereotaxically injected ibotenic acid to produce unilateral entorhinal cortex lesions in rats. We then serially examined the CA3 hippocampal region by neuronal counts, histochemistry for acetylcholinesterase, and synaptophysin immunohistochemistry. Over 12 months, the neuronal counts did not change. Acetylcholinesterase‐positive fibers were persistently but non‐progressively beginning at 3 months. Synaptophysin immunoreactivity progressively declined over 12 months. Since much of the entorhinal cortex output proceeds to CA3 via the dentate gyrus, transsynaptic degeneration is suspected.