Functional integration of the rat hippocampal tissue, transplanted into the rabbit septum

Abstract

Embryonal tissue of the rat hippocampus (E17–18) was grafted into small acute cavity within the dorsal septum of adult rabbit after interruption of septo-hippocampal connections. Histological analysis (Nissl stain), performed 6–8 weeks later, revealed surviving hippocampal grafts in 14 out of 29 grafted animals (48%). Some of the grafts were displaced into the ventricle and had only minor contact with the host septum; some others, residing in the septum, were separated from the host tissue by continuous glial scar. Six grafts (33%) were morphologically well integrated with the host septum. The grafts contained mature pyramidal neurons but their organization into layer was absent. No signs of rejection were observed in the grafts, which were not subjected to microelectrode investigation in chronic conditions. The grafts, which for 5–9 successive days were penetrated by microelectrodes, were heavily infiltrated by lymphocytes and had necrotic areas. Electrophysiological testing revealed the absence of spontaneous neuronal activity, or the presence of hypersynchronous epileptiform bursts in isolated grafts. The 4 integrated grafts, investigated electrophysiologically, contained neurons with normal spontaneous activity of two types: low-frequency discharges with complex spikes and high-frequency single spikes, sometimes with short periods of weak rhythmic modulation in the θ-range. Characteristics of spontaneous activity of the xenografted hippocampus are very close to those described in the rat hippocampus in situ. Rhythmic θ-modulation of neuronal activity appeared or increased in stability after physostigmine injection to the host, after electrical stimulation of the host's midbrain reticular formation and ventral part of diagonal band, and after multimodal sensory stimulation of the host. The frequency of θ-bursts in the grafts was identical to that of neurons of the host septum (4.5–6.5 Hz). Besides the θ-modulation sensory stimuli evoked tonic suppression or activation of discharges, phasic reactions and on-effects. Electrical stimulation of lateral septum and diagonal band evoked orthodromic and antidromic discharges of the grafted cells. Normal spontaneous and evoked activity of the grafted cells deteriorated after 5–11 successive days of microelectrode investigation. It is concluded that xenografts of nervous tissue, developing without immunosuppression, have a low rate of survival and are vulnerable to immune response after mechanical interruption of integrity of the blood-brain barrier. Nevertheless their normal activity and close functional integration with the host brain, apparently depending on development of chimeric synapses, is possible.