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.

Diseases of White Matter and Schizophrenia-Like Psychosis

“…For example, reduced input from neighbouring cells can result in neuronal cell loss, a phenomenon known as trans-synaptic degeneration (TSD) [160], which can occur following white matter dysfunction or insult and evolves slowly over many years [161]. In TSD, cells may atrophy, or undergo apoptosis in response to the decreased or absent afferent input [162],[163], or show reductions in synaptic density [164]. Although this has been best studied in lesion models, it is possible that an early static or neurodevelopmental process affectingwhite matter could result in slow changes to neuronal population number, size or dendritic arborization which could account for grey matter volumetric changes, such as those seen in schizophrenia [165].…”

Diseases of white matter and schizophrenia-like psychosis

“…For example, reduced input from neighbouring cells can result in neuronal cell loss, a phenomenon known as trans‐synaptic degeneration (TSD) [160], which can occur following white matter dysfunction or insult and evolves slowly over many years [161]. In TSD, cells may atrophy, or undergo apoptosis in response to the decreased or absent afferent input [162,163], or show reductions in synaptic density [164]. Although this has been best studied in lesion models, it is possible that an early static or neurodevelopmental process affecting white matter could result in slow changes to neuronal population number, size or dendritic arborization which could account for grey matter volumetric changes, such as those seen in schizophrenia [165].…”