Basic Concepts in Understanding Recovery of Function in Vestibular Reflex Networks during Vestibular Compensation

Unilateral peripheral vestibular lesions produce a syndrome of oculomotor and postural deficits with the symptoms at rest, the static symptoms, partially or completely normalizing shortly after the lesion due to a process known as vestibular compensation. The symptoms are thought to result from changes in the activity of vestibular sensorimotor reflexes. Since the vestibular nuclei must be intact for recovery to occur, many investigations have focused on studying these neurons after lesions. At present, the neuronal plasticity underlying early recovery from the static symptoms is not fully understood. Here we propose that knowledge of the reflex identity and input–output connections of the recorded neurons is essential to link the responses to animal behavior. We further propose that the cellular mechanisms underlying vestibular compensation can be sorted out by characterizing the synaptic responses and time course for change in morphologically defined subsets of vestibular reflex projection neurons. Accordingly, this review focuses on the perspective gained by performing electrophysiological and immunolabeling studies on a specific subset of morphologically defined, glutamatergic vestibular reflex projection neurons, the principal cells of the chick tangential nucleus. Reference is made to pertinent findings from other studies on vestibular nuclei neurons, but no comprehensive review of the literature is intended since broad reviews already exist. From recording excitatory and inhibitory spontaneous synaptic activity in principal cells, we find that the rebalancing of excitatory synaptic drive bilaterally is essential for vestibular compensation to proceed. This work is important for it defines for the first time the excitatory and inhibitory nature of the changing synaptic inputs and the time course for changes in a morphologically defined subset of vestibular reflex projection neurons during early stages of vestibular compensation

Admission profile and discharge outcomes for infants aged less than 6 months admitted to inpatient therapeutic care in 10 countries. A secondary data analysis.

Evidence on the management of acute malnutrition in infants aged less than 6 months (infants <6mo) is scarce. To understand outcomes using current protocols, we analysed a sample of 24 045 children aged 0-60 months from 21 datasets of inpatient therapeutic care programmes in 10 countries. We compared the proportion of admissions, the anthropometric profile at admission and the discharge outcomes between infants <6mo and children aged 6-60 months (older children). Infants <6mo accounted for 12% of admissions. The quality of anthropometric data at admission was more problematic in infants <6mo than in older children with a greater proportion of missing data (a 6.9 percentage point difference for length values, 95% CI: 6.0; 7.9, P < 0.01), anthropometric measures that could not be converted to indices (a 15.6 percentage point difference for weight-for-length z-score values, 95% CI: 14.3; 16.9, P < 0.01) and anthropometric indices that were flagged as outliers (a 2.7 percentage point difference for any anthropometric index being flagged as an outlier, 95% CI: 1.7; 3.8, P < 0.01). A high proportion of both infants <6mo and older children were discharged as recovered. Infants <6mo showed a greater risk of death during treatment (risk ratio 1.30, 95% CI: 1.09; 1.56, P < 0.01). Infants <6mo represent an important proportion of admissions to therapeutic feeding programmes, and there are crucial challenges associated with their care. Systematic compilation and analysis of routine data for infants <6mo is necessary for monitoring programme performance and should be promoted as a tool to monitor the impact of new guidelines on care

Presynaptic GABA(B) receptors decrease neurotransmitter release in vestibular nuclei neurons during vestibular compensation

Unilateral damage to the peripheral vestibular receptors precipitates a debilitating syndrome of oculomotor and balance deficits at rest, which extensively normalize during the first week after the lesion due to vestibular compensation. In vivo studies suggest that GABA(B) receptor activation facilitates recovery. However, the presynaptic or postsynaptic sites of action of GABA(B) receptors in vestibular nuclei neurons after lesions have not been determined. Accordingly, here presynaptic and postsynaptic GABA(B) receptor activity in principal cells of the tangential nucleus, a major avian vestibular nucleus, was investigated using patch-clamp recordings correlated with immunolabeling and confocal imaging of the GABA(B) receptor subunit-2 (GABA(B)R2) in controls and operated chickens shortly after unilateral vestibular ganglionectomy (UVG). Baclofen, a GABA(B) agonist, generated no postsynaptic currents in principal cells in controls, which correlated with weak GABA(B)R2 immunolabeling on principal cell surfaces. However, baclofen decreased miniature excitatory (mEPSC) and GABAergic inhibitory (mIPSC) events in principal cells in controls, compensating and uncompensated chickens three days after UVG, indicating the presence of functional GABA(B) receptors on presynaptic terminals. Baclofen decreased GABAergic mIPSC frequency to the greatest extent in principal cells on the intact side of compensating chickens, with concurrent increases in GABA(B)R2 pixel brightness and percentage overlap in synaptotagmin2 (Syt2)-labeled terminals. In uncompensated chickens, baclofen decreased mEPSC frequency to the greatest extent in principal cells on the intact side, with concurrent increases in GABA(B)R2 pixel brightness and percentage overlap in Syt1-labeled terminals. Altogether, these results revealed changes in presynaptic GABA(B) receptor function and expression which differed in compensating and uncompensated chickens shortly after UVG. This work supports an important role for GABA(B) autoreceptor-mediated inhibition in vestibular nuclei neurons on the intact side during early stages of vestibular compensation, and a role for GABA(B) heteroreceptor-mediated inhibition of glutamatergic terminals on the intact side in the failure to recover function