Complementariness and Functional Parcellation of Neurotrophin Actions on the Oculomotor System

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF, BDNF or NT-3 protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT. In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review we summarize these evidences and discuss them in the context of other motor systems.

Brain Stem Pursuit Pathways: Dissociating Visual, Vestibular, and Proprioceptive Inputs During Combined Eye-Head Gaze Tracking

Eye-head (EH) neurons within the medial vestibular nuclei are thought to be the primary input to the extraocular motoneurons during smooth pursuit: they receive direct projections from the cerebellar flocculus/ventral paraflocculus, and in turn, project to the abducens motor nucleus. Here, we recorded from EH neurons during head-restrained smooth pursuit and head-unrestrained combined eye-head pursuit (gaze pursuit). During head-restrained smooth pursuit of sinusoidal and step-ramp target motion, each neuron's response was well described by a simple model that included resting discharge (bias), eye position, and velocity terms. Moreover, eye acceleration, as well as eye position, velocity, and acceleration error (error = target movement – eye movement) signals played no role in shaping neuronal discharges. During head-unrestrained gaze pursuit, EH neuron responses reflected the summation of their head-movement sensitivity during passive whole-body rotation in the dark and gaze-movement sensitivity during smooth pursuit. Indeed, EH neuron responses were well predicted by their head- and gaze-movement sensitivity during these two paradigms across conditions (e.g., combined eye-head gaze pursuit, smooth pursuit, whole-body rotation in the dark, whole-body rotation while viewing a target moving with the head (i.e., cancellation), and passive rotation of the head-on-body). Thus our results imply that vestibular inputs, but not the activation of neck proprioceptors, influence EH neuron responses during head-on-body movements. This latter proposal was confirmed by demonstrating a complete absence of modulation in the same neurons during passive rotation of the monkey's body beneath its neck. Taken together our results show that during gaze pursuit EH neurons carry vestibular- as well as gaze-related information to extraocular motoneurons. We propose that this vestibular-related modulation is offset by inputs from other premotor inputs, and that the responses of vestibuloocular reflex interneurons (i.e., position-vestibular-pause neurons) are consistent with such a proposal.

New Mechanism That Accounts for Position Sensitivity of Saccades Evoked in Response to Stimulation of Superior Colliculus

Moschovakis, A. K., Y. Dalezios, J. Petit, and A. A. Grantyn. New mechanism that accounts for position sensitivity of saccades evoked in response to stimulation of superior colliculus. J. Neurophysiol. 80: 3373–3379, 1998. Electrical stimulation of the feline superior colliculus (SC) is known to evoke saccades whose size depends on the site stimulated (the “characteristic vector” of evoked saccades) and the initial position of the eyes. Similar stimuli were recently shown to produce slow drifts that are presumably caused by relatively direct projections of the SC onto extraocular motoneurons. Both slow and fast evoked eye movements are similarly affected by the initial position of the eyes, despite their dissimilar metrics, kinematics, and anatomic substrates. We tested the hypothesis that the position sensitivity of evoked saccades is due to the superposition of largely position-invariant saccades and position-dependent slow drifts. We show that such a mechanism can account for the fact that the position sensitivity of evoked saccades increases together with the size of their characteristic vector. Consistent with it, the position sensitivity of saccades drops considerably when the contribution of slow drifts is minimal as, for example, when there is no overlap between evoked saccades and short-duration trains of high-frequency stimuli.

Utriculoocular reflex arc of the cat

1. Intracellular recordings of synaptic potentials in extraocular motoneurons were studied to determine the connectivities between the utricular nerve and the extraocular motoneurons in cats. 2. Stimulating electrodes were placed within the left utricular nerve, while other branches of the vestibular nerve were removed. Subsequently, the N1 field potentials evoked by utricular nerve stimulation were recorded in the vestibular nuclei. The potential typically grew until reaching a plateau (submaximal stimulation). Stimulus spread to the other nerve branches appeared as an additional increase in N1 amplitude after the plateau discontinued (supramaximal stimulation). 3. Intracellular recordings were made from 200 identified motoneurons in the bilateral III, IV, and VI cranial nuclei. 4. Stimulation of the utricular nerve at submaximal intensity evoked a longer latency depolarizing and hyperpolarizing potentials in contra- and ipsilateral medial rectus motoneurons, respectively. Complex potentials with longer latencies also were recorded in ipsilateral inferior oblique and contralateral trochlear motoneurons after stimulation of the utricular nerve at a submaximal intensity. Monosynaptic and disynaptic connections between the utricular nerve and ipsilateral abducens motoneurons and interneurons were recorded as described previously. 5. The results of the present study confirm our initial findings that a disynaptic pathway from the utricular nerve to contralateral trochlear motoneurons is absent or very poorly developed, whereas polysynaptic circuits from the utricular nerve to inferior oblique and trochlear motoneurons may play a role in eye rotation during head tilt.