Intravenous injection of 3-33 nmol/kg of substance P (SP) caused pressor and tachycardic responses in anesthetized rats. The responses were not blocked by a ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine blocked both responses. β-Adrenoceptor blockade attenuated only the tachycardic response, and α-adrenoceptor blockade attenuated only the pressor response. These findings indicated that the effects of SP to increase blood pressure and heart rate are due to sympathetic ganglion stimulation. Studies with adrenalectomized rats showed that stimulation of the adrenals by SP contributes to both responses but makes a greater contribution to the tachycardic response. These observations raise the possibility that the tachykinin innervation of sympathetic ganglia and the adrenal medulla may be involved in the local regulation of blood pressure and heart rate.

Damage to peripheral nerves can cause extensive functional reorganization of the adult mammalian nervous system. In fact, studies in non-human adult mammals have shown somatotopic reorganization as well as changes in receptive field properties throughout the somatosensory neuraxis following damage to peripheral nerves. Chronic changes in receptive fields and response properties have also been reported in the trigeminal brainstem nuclear complex (TBNC) following trigeminal nerve damage in both neonates and adults. Significant functional reorganization within subnucleus interpolaris (SpVi) was also apparent in rats subjected to infraorbital nerve transection. Several mechanisms have been proposed to account for many of the observed functional changes. They include: misdirected peripheral regrowth and changes in central arbor morphology of damaged primary afferents; peripheral and central sprouting of undamaged primary afferents; changes in morphology of second order neurons; and sprouting of central afferents to the TBNC. In addition, central monoaminergic neurons have been demonstrated to undergo considerable regeneration or collateral sprouting following direct damage or disruption of their sensory input. These monoaminergic neurons normally modulate the function of their targets. Thus, damage induced reorganization of monoaminergic projections to the TBNC could alter the response properties of cells within this region. The normal effects of monoaminergic inputs to SpVi have not yet been fully determined. We intend to use the neurotoxin 5,7-dihydroxytryptamine (specific for the destruction of serotonin and norepinephrine containing neurons) in combination with the antidepressant drug desmethylimipramine (used to protect norepinephrine containing neurons) to selectively destroy serotonergic fibers in SpVi in order to describe the normal functional role of serotonergic inputs to this region. This manipulation produced a significant change in : i) the types of peripheral receptor surfaces that activate cells in SpVi, and ii) rate of spontaneous activity. These changes reflect some of the functional alternatives observed after infraorbital nerve damage and suggest a role for serotonergic afferents in these changes. / Master of Science

Spinal cord injuries (SCI) sever communication between supraspinal centers and the central pattern generator (CPG) responsible for locomotion. Because the CPG is intact and retains the ability to initiate locomotor activity, it can be accessed electrically and pharmacologically. The goal of this thesis was to identify and characterize a novel spinal cord surface site along the sacral dorsal column (sDC) for electrically evoking locomotor-like activity in the neonatal rat spinal cord. Stimulation of the sDC robustly activated rhythmic left-right alternation in flexor-related ventral roots that was dependent on the activation of high-threshold C fiber afferents. The C fibers synapsed onto spinal neurons, which project to the lumbar segments as part of a pathway dependent on purinergic, adrenergic, and cholinergic receptor activation. In ventral roots containing only somatic efferents, rhythmic activity was rarely recruited. However, in ventral roots containing both autonomic and somatic efferents, sacral dorsal column stimulation recruited autonomic efferent rhythms, which subsequently recruited somatic efferent motor rhythms. The efferent rhythms revealed a half-center organization with very low stimulation frequencies, and the evoked alternating bursts entrained to the stimuli. Similar entrainment was seen when sDC stimuli were applied during ongoing neurochemically-induced locomotor rhythms. The rhythmic patterns evoked by sDC stimulation operated over a limited frequency range, with a discrete burst structure of fast-onset, frequency-independent peaks. In comparison, neurochemically-induced locomotor bursts operated over a wide frequency range and had slower time to peaks that varied with burst frequency. The overall findings support the discovery of an autonomic efferent pattern generator that is recruited by sacral visceral C fiber afferents. It is hoped that this research will advance the understanding of afferent activation of the lumbar central pattern generator and potentially provide insight useful for future development and design of neuroprosthetic devices.