Loss and reacquisition of hippocampal synapses after selective destruction of CA3-CA4 afferents with kainic acid.

Intraventricular injections of kainic acid were used to destroy the hippocampal CA3-CA4 cells bilaterally in rats, thus denervating the inner third of the molecular layer of the fascia dentata and stratum radiatum of area CA1. Electron microscopic studies showed that this lesion reduced the synaptic density of the CA1 stratum radiatum by an average of 86%. The synaptic density of the inner third of the dorsal dentate molecular layer declined by two-thirds and the corresponding zone of the ventral dentate molecular layer by about half. Within 6-8 weeks the synaptic density of these laminae had been restored to the control value or nearly so. In the CA1 stratum radiatum about 72% of the synaptic contacts destroyed by the lesion were replaced, the inner third of the ventral dentate molecular layer recovered 75% of its lost synapses and the inner third of the dorsal dentate molecular layer apparently recovered virtually all of them. The newly formed synapses did not differ noticeably from those normally present. A kainic acid lesion reduced the synaptic density of the outer two-thirds of the dentate molecular layer by 30% within 3-5 days, despite a virtual absence of presynaptic degeneration in that zone. This result implies a substantial disconnection of perforant path synapses. It did not appear to depend on the extent of denervation of the inner zone. The loss of perforant path synapses was completely reversible. We suggest that the dentate granule cells shed a portion of their synapses in response to a substantial loss of neurons to which they project and regained them when their axons had formed new synaptic connections.