A series of experiments are aimed at learning how neurons in the dorsal horn of the mammalian spinal cord are synaptically connected. The focus will be on neurons in the deep layers, Rexed's laminae III to VI, a synaptic station for fibers of tactile, hair and muscle receptors and an area from which several major ascending sensory tracts originate. The basic anatomical and physiological principles that govern local synaptic interactions between dorsal horn neurons will be investigated in a new in vitro mammalian spinal cord slice preparation that permits spinal neurons to be functionally identified according to their input from cutaneous receptors. Simultaneous, intracellular recordings will be sought using two, independently targetable micropipette electrodes. Synaptic linkage between pairs of neurons will be directly tested and characterized according to whether it is excitatory or inhibitory and whether local synaptic transmission in the dorsal horn is mediated via axonal or dendrodendritic pathways. We will investigate how activity in these local circuits modulates responses of dorsal horn neurons to cutaneous stimuli. Direct anatomical evidence of local connectivity between dorsal horn neurons will be sought, with an emphasis on how these connections are spatially organized onto postsynaptic neurons by iontophoretically depositing horseradish peroxidase or other intracellular markers into identified neurons. Other experiments will seek to determine the ionic basis for synaptic potentials mediated by local connections and to identify possible neurotransmitters that mediate local synaptic transmission in the dorsal horn. The results of this work will facilitate an understanding of signal processing in major somatosensory pathways and local somatic motor control pathways. These insights are essential for a knowledgeable approach to sensory deficits and central pain secondary to spinal cord injury and disease.
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