Ottavio Pompeiano, M.D. - US grants

One of the main objectives of the proposed research project is to find out whether in addition to excitatory vestibulospinal neurons, neurons originating from the inhibitory area of the medullary reticular formation intervene in the labyrinthine and cervical control of posture. In particular it would be of interest 1) to know whether presumably inhibitory reticulospinal (iRS) neurons controlling the limb musculature show a response patterns opposite to that displayed by the excitatory vestibulospinal (eVS) neurons for the same direction of animal orientation and neck rotation. If so, the increased activity of the extensor motoneurons innervating the limo musculature, which occurs for instance during ipsilateral tilt, would depend upon both an increased discharge of eVS neurons and a reduced discharge of iRS neurons of the medulla; 2) to investigate whether the resting discharge rate of the presumably iRS neurons, which is greatly reduced after decerebration, undergo a steady increase following neurochemical activation of a cholinergic system, leading to a suppression of the decerebrate rigidity; this state-dependent behavior of the iRS neurons can be used as an experimental condition 3) to find out whether the gain of the EMG response of limb extensors to animal tilt or neck rotation depends upon the activity of this cholinergic system, so that the higher the firing rate of the reticulospinal neurons in the animal at rest the greater would be the disinhibition which affects the ext. motoneurons during animal tilt or neck rotation, thus increasing the response gain of the extensor muscles to vestibular and neck stimulation. These experiments may answer the question as to whether the reticulospinal inhibitory system operates as a variable gain regulator acting at motoneuronal level during the vestibular and neck reflexes. A further objective is 4) to identify the inhibitory interneurons utilized by the reticulospinal neurons during the vestibular reflexes. In particular, the activity of Renshaw cells coupled with hindlimb extensor motoneurons will be recorded during natural stimulation of lybyrinth receptors, to find out whether these cells driven by the reticulospinal neurons may actually determine the response gain of limb extensors to a given labyrinthine signal.

The main aim of the proposed projects is to investigate the role that the central noradrenergic system, located in the locus coeruleus (LC), exerts in the static and dynamic control of posture and movements. It was previously shown that the LC exerts a facilitatory influence on posture either directly, by utilizing the facilitatory coeruleospinal (CS) pathway or indirectly, by suppressing the discharge of dorsal pontine reticular formation (pRF) neurons and the related medullary inhibitory reticulospinal (RS) system. Since CS as well as RS neurons respond to sinusoidal stimulation of labyrinth receptors, thus intervening in the gain regulation of vestibulospinal (VS) reflexes, experiments will be performed in decerebrate cats to identify the role that putative excitatory (or inhibitory) neurotransmitters and neuromodulators, locally applied within the LC, exert on posture as well as on the gain of VS reflexes. A second series of experiments will be carried out in unanaesthetized cats to find out whether changes in the background discharge of LC neurons and/or the related pRF neurons, induced by local injection of appropriate neurotransmitter-agonists, may modify the amplitude of the postural adjustments which occur during the forelimb flexion elicited by unilateral stimulation of the corresponding motor cortex, without affecting the limb movement. In addition to descending projections to the spinal cord, the LC sends afferent projection to the cerebellum. Experiments will be performed to investigate whether changes in the activity of the noradrenergic afferent projections ending either within the cerebellar vermis or within the flocculus may modify the gain of the VS reflexes in decerebrate cats, as well as the adaptive changes in the vestibulo-ocular reflexes (VOR) gain normally occurring in unanaesthetized rabbits.