Anatomical evidence for an anticonvulsant relay in the rat ventromedial medulla

Authors

  • Safa Shehab,

    1. Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al-Ain, UAE
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  • David McGonigle,

    1. Laboratory of Human Anatomy, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
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    • Present address: Centre for Functional Imaging Studies (CFIS), SHEFC Brain Imaging Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

  • David I. Hughes,

    1. Spinal Cord Group, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
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  • Andrew J. Todd,

    1. Spinal Cord Group, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
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  • Peter Redgrave

    1. Department of Psychology, University of Sheffield, Sheffield, S10 2TP, UK
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Safa Shehab, as above.
E-mail: s.shehab@uaeu.ac.ae

Abstract

Pharmacological manipulation of the ventrolateral pontine reticular formation (vlPRF) of rats has an anticonvulsant effect in the maximal electroshock model of epilepsy. This study presents three anatomical experiments that determine the efferent projections from this region likely to mediate this anticonvulsant effect. In the first, the anterograde tracer biotinylated dextran amine (BDA) was injected into the vlPRF. A strong projection to the ventromedial medullary reticular formation (vmMRF) was revealed which continued only weakly to the spinal cord. In the second experiment, double-label procedures were used to indicate whether the BDA-labelled terminals from the vlPRF make contacts with neurons in vmMRF, retrogradely labelled with cholera-toxin B subunit from the lumbar spinal cord. Sections of the vmMRF were examined by: (i) light microscopy which showed significant overlap between terminals from vlPRF and retrogradely-labelled reticulospinal cells; (ii) confocal microscopy which showed labelled terminals in close association with reticulospinal cell bodies; and (iii) electron microscopy which showed vlPRF terminals making synaptic contact with reticulospinal neurons. Finally, immunohistochemical procedures in combination with anterograde tracing revealed that significant numbers of terminals labelled from vlPRF were also positive for markers of glutamatergic or GABAergic neurotransmission. This suggests that the projection from the vlPRF to the vmMRF is likely to include several different functional components. These connections could represent a final critical link of an anticonvulsant circuit that originates in the dorsal midbrain and projects via relays in the vlPRF and the vmMRF to interact with the low-level motor circuitry in the spinal cord.

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