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Title: A study of projections from the substantia nigra and the ventral tegmental area to the hippocampus of the rat
Author: Spencer, Philip Mark
ISNI:       0000 0001 3474 8007
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1986
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The anatomical organisation of projections from the ventral midbrain and the distribution of their terminals throughout the hippocampus, were studied using retrograde fluorescent-labelling and degeneration techniques. By taking advantage of the potential fluorescent properties of monoamines, the retrograde-tracing studies were extended to assess the dopamine-content of any filled cells. In vivo electrophysiological studies were also performed to characterise the events which occur in the hippocampus following stimulation of the substantia nigra or the ventral tegmental area. Pharmacological manipulations were then carried out to test for the possible involvement of certain neurotransmitters. The retrograde-tracing studies identified a projection from the ventral tegmental area to both the ventral and dorsal hippocampus. Only 5-10% of the retrogradely-filled cells were also fluorescent for dopamine, indicating the existence of a substantial non-dopaminergic projection. A pathway from the subsantia nigra was detected only by degeneration studies. Terminals, identified using the Fink-Heimer technique, were confined to the ventral hippocampus ipsilateral to the chemical lesion. The projection from the ventral tegmental area could not be detected using similar degeneration techniques. Electrical stimulation of either nucleus resulted in a profound suppression of pyramidal cell activity throughout the CA1 region of the hippocampus, but not the dentate gyrus. This inhibition was expressed bilateral to the site of midbrain stimulation, and was a long-lasting, postsynaptic event. Systemic or iontophoretic application of dopamine antagonists failed to block the inhibition, suggesting that this was mediated by a non-dopaminergic pathway. Iontopheresis of the GABA A receptor antagonist bicuculline did not block the inhibition and furthermore, flurazapam did not potentiate the effects evoked by midbrain stimulation. These observations suggest that GABA A receptors are not involved in mediating the inhibition. However, the inhibitory effects of stimulating the substantia nigra or the ventral tegmental area were abolished seven days following the intracerebroventricular injection of kainic acid. This treatment is known to destroy CA3 pyramidal cells and is believed to interfere with inhibitory interneurone function in CA1, by attenuating both GABA A and GABA B receptor-mediated events. This work substantiates previous anatomical descriptions of projections to the hippocampus from the substantia nigra and the ventral tegmental area. Bilateral, postsynaptic modulation of hippocampal pyramidal cell discharge was found to follow stimulation of either of these midbrain nuclei. The involvement of dopamine in this pathway and its role in mediating the inhibiton described is questioned, and the possible involvement of GABA B receptors is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Human anatomy & human histology