The Ventral Posterior Lateral Thalamus Preferentially Encodes Externally Applied Versus Active Movement: Implications for Self-Motion Perception.

Successful interaction with our environment requires that voluntary behaviors be precisely coordinated with our perception of self-motion. The vestibular sensors in the inner ear detect self-motion and in turn send projections via the vestibular nuclei to multiple cortical areas through 2 principal thalamocortical pathways, 1 anterior and 1 posterior. While the anterior pathway has been extensively studied, the role of the posterior pathway is not well understood. Accordingly, here we recorded responses from individual neurons in the ventral posterior lateral thalamus of macaque monkeys during externally applied (passive) and actively generated self-motion. The sensory responses of neurons that robustly encoded passive rotations and translations were canceled during comparable voluntary movement (~80% reduction). Moreover, when both passive and active self-motion were experienced simultaneously, neurons selectively encoded the detailed time course of the passive component. To examine the mechanism underlying the selective elimination of vestibular sensitivity to active motion, we experimentally controlled correspondence between intended and actual head movement. We found that suppression only occurred if the actual sensory consequences of motion matched the motor-based expectation. Together, our findings demonstrate that the posterior thalamocortical vestibular pathway selectively encodes unexpected motion, thereby providing a neural correlate for ensuring perceptual stability during active versus externally generated motion.

Local population synchrony and the encoding of eye position in the primate neural integrator.

Encoding horizontal eye position in the oculomotor system occurs through temporal integration of eye velocity inputs to produce tonic outputs. The nucleus prepositus is commonly believed to be the "neural integrator" that accomplishes this function through the activity of its ensemble of predominantly burst-tonic neurons. Single-unit characterizations and labeling studies of these neurons have suggested that their collective output is achieved through local feedback loops produced by direct connections between them. If this is the case, then the ensemble of burst-tonic neurons should exhibit correlated activity. To obtain electrophysiological evidence of local interactions between neurons, we simultaneously recorded pairs (n = 29) of burst-tonic neurons in the nucleus prepositus of rhesus macaque monkeys using eight-channel linear microelectrode arrays. We computed the magnitude of synchrony between their spike trains as a function of eye position during ocular fixations and as a function of distance between neurons. Importantly, we found that neurons exhibit unexpected levels of positive synchrony, which is maximal during contralateral fixations and weakest when neurons are located far apart from one another (>300 µm). Together, our results support a role for shared inputs to ipsilateral pairs of burst-tonic neurons in the encoding of eye position in the primate nucleus prepositus.

Neuronal detection thresholds during vestibular compensation: contributions of response variability and sensory substitution.

The vestibular system is responsible for processing self-motion, allowing normal subjects to discriminate the direction of rotational movements as slow as 1-2 deg s(-1). After unilateral vestibular injury patients' direction-discrimination thresholds worsen to ∼20 deg s(-1), and despite some improvement thresholds remain substantially elevated following compensation. To date, however, the underlying neural mechanisms of this recovery have not been addressed. Here, we recorded from first-order central neurons in the macaque monkey that provide vestibular information to higher brain areas for self-motion perception. Immediately following unilateral labyrinthectomy, neuronal detection thresholds increased by more than two-fold (from 14 to 30 deg s(-1)). While thresholds showed slight improvement by week 3 (25 deg s(-1)), they never recovered to control values - a trend mirroring the time course of perceptual thresholds in patients. We further discovered that changes in neuronal response variability paralleled changes in sensitivity for vestibular stimulation during compensation, thereby causing detection thresholds to remain elevated over time. However, we found that in a subset of neurons, the emergence of neck proprioceptive responses combined with residual vestibular modulation during head-on-body motion led to better neuronal detection thresholds. Taken together, our results emphasize that increases in response variability to vestibular inputs ultimately constrain neural thresholds and provide evidence that sensory substitution with extravestibular (i.e. proprioceptive) inputs at the first central stage of vestibular processing is a neural substrate for improvements in self-motion perception following vestibular loss. Thus, our results provide a neural correlate for the patient benefits provided by rehabilitative strategies that take advantage of the convergence of these multisensory cues.

The nucleus prepositus predominantly outputs eye movement-related information during passive and active self-motion.

Maintaining a constant representation of our heading as we move through the world requires the accurate estimate of spatial orientation. As one turns (or is turned) toward a new heading, signals from the semicircular canals are relayed through the vestibular system to higher-order centers that encode head direction. To date, there is no direct electrophysiological evidence confirming the first relay point of head-motion signals from the vestibular nuclei, but previous anatomical and lesion studies have identified the nucleus prepositus as a likely candidate. Whereas burst-tonic neurons encode only eye-movement signals during head-fixed eye motion and passive vestibular stimulation, these neurons have not been studied during self-generated movements. Here, we specifically address whether burst-tonic neurons encode head motion during active behaviors. Single-unit responses were recorded from the nucleus prepositus of rhesus monkeys and compared for head-restrained and active conditions with comparable eye velocities. We found that neurons consistently encoded eye position and velocity across conditions but did not exhibit significant sensitivity to head position or velocity. Additionally, response sensitivities varied as a function of eye velocity, similar to abducens motoneurons and consistent with their role in gaze control and stabilization. Thus our results demonstrate that the primate nucleus prepositus chiefly encodes eye movement even during active head-movement behaviors, a finding inconsistent with the proposal that this nucleus makes a direct contribution to head-direction cell tuning. Given its ascending projections, however, we speculate that this eye-movement information is integrated with other inputs in establishing higher-order spatial representations.

Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis.

Maternal diabetes adversely affects preimplantation embryo development and pregnancy outcomes. The objective of this study was to determine whether diabetes has an impact at an earlier stage of development, the preovulatory oocyte. Models of both acute and chronic insulin-dependent diabetes were used. Acute hyperglycemia was induced by a single streptozotocin injection. Akita mice, which harbor an autosomal dominant mutation causing them to be chronically hypoinsulinemic and hyperglycemic, were used. In both models, preovulatory oocytes were markedly smaller when compared with control animals. A significantly greater number of control oocytes had progressed to meiotic maturation before diabetic oocytes. Both models were found to have smaller, less developed ovarian follicles with a greater number of apoptotic foci by histological evaluation as well as by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining. Immunohistochemistry displayed a greater amount of TNF-related apoptosis-inducing ligand (TRAIL) and KILLER, a key murine ligand and receptor involved in the extrinsic pathway, expressed in cumulus cells from hyperglycemic mice compared with controls, suggesting that this apoptotic pathway may be up-regulated under diabetic stress. Elevated KILLER expression was also confirmed through Western blotting. Connexin-43 expression was found to be lower by immunohistochemistry and Western blot analysis in the diabetic samples. Both models of maternal hyperglycemia and hypoinsulinemia may have a detrimental effect on oocyte maturation and development as detailed by the smaller sizes of oocytes and developing ovarian follicles, the lowered percentage reaching germinal vesicle breakdown, and the greater amount of apoptosis. In addition, there may be dysfunctional or decreased communication in diabetic oocytes, as demonstrated by lower expression of connexin-43.